INSTITUTO DE PSIQUIATRIA - IPUB

CENTRO DE CIÊNCIAS DA SAÚDE - CCS

UNIVERSIDADE FEDERAL DO RIO DE JANEIRO

ALINE SARDINHA MENDES SOARES DE ARAÚJO

EXERCÍCIO FÍSICO NO TRANSTORNO DE PÂNICO:

ASPECTOS FISIOLÓGICOS E CLÍNICOS

RIO DE JANEIRO
2013
 INSTITUTO DE PSIQUIATRIA - IPUB
CENTRO DE CIÊNCIAS DA SAÚDE - CCS
UNIVERSIDADE FEDERAL DO RIO DE JANEIRO

ALINE SARDINHA MENDES SOARES DE ARAÚJO

EXERCÍCIO FÍSICO NO TRANSTORNO DE PÂNICO:

ASPECTOS FISIOLÓGICOS E CLÍNICOS

Tese de doutorado submetida ao corpo

docente do Programa de Pós-Graduação
em Psiquiatria e Saúde Mental
(PROPSAM) do Instituto de Psiquiatria da
Universidade Federal do Rio de Janeiro,
como parte dos requisitos necessários
para a obtenção do grau de Doutor em
Saúde Mental.

ORIENTADOR
Antonio Egidio Nardi - Professor Titular (IPUB/UFRJ)

RIO DE JANEIRO
Agosto de 2013

1
 Sardinha, Aline
Exercício físico no Transtorno de Pânico: aspectos fisiológicos e
clínicos /Aline Sardinha Mendes Soares de Araújo. -- Rio de Janeiro:
UFRJ, IPUB. 2013. 107p.

Inclui referências bibliográficas.

Orientador: Antonio Egidio Nardi.

Tese de Doutorado - Universidade Federal do Rio de Janeiro,
Instituto de Psiquiatria, 2013.

1. Transtorno de Pânico. 2. Exercício Físico. 3. Risco Cardiovascular.

4.Terapia Cognitivo-Comportamental. 5. Ansiedade Cardíaca. I.Nardi,
Antônio Egídio. II. Universidade Federal do Rio de Janeiro, Instituto
de Psiquiatria. III. Título.

2
 ALINE SARDINHA MENDES SOARES DE ARAÚJO

EXERCÍCIO FÍSICO NO TRANSTORNO DE PÂNICO:

ASPECTOS FISIOLÓGICOS E CLÍNICOS

Tese de doutorado submetida ao corpo

docente do Programa de Pós-Graduação
em Psiquiatria e Saúde Mental
(PROPSAM) do Instituto de Psiquiatria da
Universidade Federal do Rio de Janeiro,
como parte dos requisitos necessários
para a obtenção do grau de Doutor em
Saúde Mental.

_______________________________________
Antônio Egidio Nardi - Presidente
Doutor em Psiquiatria e Professor Titular
Universidade Federal do Rio de Janeiro

_______________________________________
Marcele Regine de Carvalho
Doutora em Saúde Mental
Professora da Universidade Federal do Rio de Janeiro

_______________________________________
Angela Josefina Donato Oliva
Doutora em Psicologia do Desenvolvimento Humano e Professora Adjunta
Universidade Estadual do Rio de Janeiro

_______________________________________
Ivan Luiz de Vasconcellos Figueira
Doutor em Psiquiatria e Professor Adjunto
Universidade Federal do Rio de Janeiro

_______________________________________
Claudio Domenico Sahione Schettino
Doutor em Cardiologia
Universidade Federal do Rio de Janeiro

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Resumo

SARDINHA, Aline. Exercício físico no transtorno de pânico: aspectos fisiológicos e

clínicos. Rio de Janeiro, 2013. Tese (Doutorado em Saúde Mental) – Instituto de
Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 2013.

Para muitos pacientes com Transtorno de Pânico (TP), a prática de exercícios físicos
pode ser uma situação ansiogênica, dada a similaridade entre a ativação
autonômica desencadeada pelo exercício e os ataques de pânico (AP), contribuindo
para uma esquiva fóbica desta atividade. Uma consequência desta estratégia de
esquiva é tornar os pacientes com TP mais expostos aos riscos de um estilo de vida
sedentário, o que pode ser especialmente prejudicial à saúde, aumentando o risco
cardiovascular primário e secundário, além de um significativo impacto negativo na
qualidade de vida. Esta tese é composta por uma coletânea de artigos científicos
que relatam estudos realizados pela autora sobre este tema ao longo do curso de
doutorado. Tais pesquisas visaram clarificar a relação entre ansiedade e doença
cardiovascular, tanto em pacientes saudáveis quanto em cardiopatas, bem como
compreender o impacto da prática regular de exercícios físicos no comportamento
da ansiedade em cardiopatas e pacientes com TP. Os dois primeiros artigos desta
tese tratam da relação entre ansiedade, pânico e risco cardiovascular, passando
tanto por aspectos fisiológicos quanto comportamentais, bem como seus prováveis
mecanismos intermediários, como as alterações autonômicas, vasculares e a
síndrome metabólica. Um elemento importante para a abordagem da associação
entre ansiedade e doença cardiovascular é o conceito de ansiedade cardíaca. Nesse
sentido, um dos estudos desta tese apresenta a versão traduzida e validada para a
população brasileira de um questionário para avaliar a ansiedade cardíaca em
cardiopatas, de modo a fundamentar a tomada de decisão clínica sobre a
necessidade de encaminhamento do paciente para o tratamento específico da
ansiedade. Este trabalho inclui ainda um artigo que relata um estudo transversal de
da prevalência de ansiedade relacionada à saúde e de comorbidades psiquiátricas
em pacientes cardiopatas que praticam exercício supervisionado regularmente e
outro de caso-controle que mostra que cardiopatas fisicamente ativos apresentam
menos comorbidades e menores níveis de ansiedade cardíaca do que cardiopatas
sedentários. Estes resultados estão em consonância com a revisão da literatura que
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aponta para a possibilidade de os exercícios físicos desempenharem um papel
potencialmente importante na saúde mental, e também especificamente no
tratamento do TP, entretanto, pouco se sabe sobre os mecanismos através dos
quais este efeito se dá e quais as melhores estratégias terapêuticas. Nesse sentido,
esta tese inclui a apresentação de um protocolo de exercícios físicos aeróbicos
supervisionados especialmente desenvolvido e testado para o tratamento do TP e os
resultados obtidos na adição deste protocolo ao tratamento de pacientes medicados
em comparação com pacientes que receberam apenas medicação. A partir destes
dados, foi possível aprofundar a compreensão acerca do impacto da prática de
exercício em aspectos específicos da psicopatologia do pânico e sua interação com
variáveis cardiorrespiratórias, de modo a determinar o papel dos exercícios no
tratamento do TP. Por último, os dados sobre a prática de exercícios em pacientes
com TP permitem aventar que a hipersensibilidade aos sintomas de ansiedade
poderia ser tratada, no âmbito da Terapia Cognitivo Comportamental (TCC),
utilizando a prática supervisionada de exercícios físicos como uma ferramenta de
dessensibilização por exposição interoceptiva, de modo a promover habituação aos
sintomas físicos. No contexto da TCC, a prescrição de exercícios pode ter um
impacto indireto também nos aspectos cognitivos relacionados TP, como a
ansiedade cardíaca, a sensibilidade à ansiedade e as cognições agorafóbicas,
permitindo, a partir da exposição, a reestruturação de crenças relacionadas à
vulnerabilidade/fragilidade do organismo. É também parte desta tese a proposta de
um protocolo de treinamento aeróbico intervalado e a apresentação de seus
resultados com um caso clínico piloto de uma paciente sendo tratada
concomitantemente com TCC e psicofármacos.

5
Abstract

SARDINHA, Aline. Exercício físico no transtorno de pânico: aspectos fisiológicos e

clínicos. Rio de Janeiro, 2013. Tese (Doutorado em Saúde Mental) – Instituto de
Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 2013.

Panic disorder (PD) patients report various combinations of autonomic manifestations

during panic attacks (PA). A major symptom, however, is the presence of anxiety
concerning the occurrence of panic symptoms and stimuli perceived as threatening to
the physical and mental health. PD patients are more sensitive to interoceptive cues
that trigger autonomic changes and therefore, anxiety and PA. For numerous patients
with PD, exercising may be considered anxiogenic, given the similarity between the
autonomic activation triggered by exercise and panic symptoms, contributing to a
phobic avoidance of this activity. A potential consequence of this strategy is to
increase the cardiovascular risk, associated to a sedentary lifestyle, as well as its
significant negative impact on quality of life. The present thesis consists of a
collection of scientific articles reporting studies conducted by the author on this topic
throughout the doctoral program. Such research aimed to clarify the relationship
between anxiety and cardiovascular disease, both in healthy subjects and in cardiac
patients, as well as understand the impact of regular exercise on anxiety behavior in
cardiac and PD patients. The first two articles aim to further comprehend the
relationship between anxiety, panic and cardiovascular risk, from both physiological
and behavioral perspectives, as well as their probable underlying mechanisms,
especially autonomic changes, vascular deficits and metabolic syndrome. An
important element in the approach of the association between anxiety and
cardiovascular disease is the concept of cardiac anxiety. In this sense, one of the
studies of this thesis presents the Brazilian portuguese validated version of a
questionnaire to assess the cardiac anxiety in cardiac patients, aimed to inform
clinical decisions on the need for patient referral for the specific treatment of anxiety.
This work also includes an article that reports a cross-sectional study of the
prevalence of health-related anxiety and psychiatric comorbidity in cardiac patients
that attend to a supervised exercise program and one case-control study showing
that physically active patients present less psychiatric comorbidities and lower levels

6
of cardiac anxiety than sedentary cardiac patients. These results are in line with the
review of literature that points to a potentially important role of physical exercise in
mental health, specifically in the treatment of PD. Little is known, however, about the
mechanisms implicated in the observed positive effect and the best therapeutic
strategies. In this sense, this thesis includes the proposal of a supervised aerobic
exercise protocol specially developed and tested for the treatment of PD and the
results of its addition to the treatment of patients already treated with
benzodiazepines and antidepressants, compared with patients who received only
medication. From these results, it was possible to deepen our understanding of the
impact of exercise training on specific aspects of the psychopathology of panic and
its interaction with cardiorespiratory variables in order to further understand the role
of exercise in the treatment of PD. Finally, data on exercise in patients with PD
suggest that hypersensitivity to anxiety symptoms could be treated within the
rationale of Cognitive Behavioral Therapy (CBT) using the supervised exercise
practice as a tool for interoceptive exposure, in order to promote habituation to
physical symptoms. In the context of CBT, exercise prescription might also have an
indirect impact on cognitive aspects related to PD, such as cardiac anxiety, anxiety
sensitivity and agoraphobic cognitions, allowing, from exposure, cognitive
restructuring of health vulnerability beliefs. It is also part of this thesis a paper
proposing an aerobic interval training protocol and presenting its results with a pilot
clinical case of a patient being treated concurrently with CBT and pharmacotherapy.

7
 SUMÁRIO

Apresentação p.12

Introdução p.14

Artigo 1 – Anxiety, panic disorder and coronary artery disease: issues p. 23

concerning physical exercise and cognitive behavioral therapy

Artigo 2 - The role of anxiety in metabolic syndrome p.35

Artigo 3 – Brazilian Portuguese validated version of the Cardiac p.45

Anxiety Questionnaire

Artigo 4 - Prevalência de transtornos psiquiátricos e ansiedade p. 54

relacionada à saúde em coronariopatas participantes de um programa
de exercício supervisionado

Artigo 5 - Psychiatric disorders and cardiac anxiety in exercising and p. 61

sedentary coronary artery disease patients: a case-control study

Artigo 6 – The mediation role of psychological and cardiorespiratory p. 69

variables in the therapeutic effect of an aerobic exercise protocol for
Panic Disorder

Artigo 7 – Treinamento físico intervalado como ferramenta na Terapia p. 95

Cognitivo Comportamental do transtorno de pânico

Conclusões p. 100

Referências p. 103

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 DEDICATÓRIA

Para ARAUJO, CGS.

O alterego pesquisador do melhor pai do mundo.

9
 AGRADECIMENTOS

Em primeiro lugar, ao professor Antonio Egidio Nardi, orientador desta tese,

meu orientador também no mestrado e coordenador do Laboratório do Pânico e
Respiração (LABPR). Em 2006, ainda na graduação, o Prof. Egidio me acolheu em
seu laboratório, mesmo extra oficialmente e sem um tema de estudo definido. Desde
então, o LABPR tem sido um ambiente de ricas trocas acadêmicas interdisciplinares,
de experiências clínicas e pessoais em diversas áreas. Obrigada, professor, pelo
apoio ao longo de todos esses anos, pela torcida, pelas oportunidades de
crescimento profissional, pelos desafios acadêmicos e também pela compreensão
nos momentos de menor produção. A forma como o Prof Egidio conduz não apenas
nossas pesquisas, mas todo o funcionamento do LABPR, permite a nós, seus
alunos, desenvolver autonomia ao mesmo tempo em que acolhe e nos ajuda a
solucionar as dificuldades de forma segura. Obrigada pelas respostas imediatas,
pela estrutura e pelas condições de trabalho diferenciadas do LABPR, por me
permitir iniciar uma nova linha de pesquisa e estabelecer, para tal, as inúmeras
parcerias necessárias.
Ao Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq),
A Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), ao
Instituto Nacional de Ciência Tecnológica Translational Medicine (INCT-TM), à
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) e ao
Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (IPUB) pelo apoio
financeiro e estrutural.
Aos colegas e funcionários do LABPR, muitos ao longo destes sete anos de
convivência verdadeiros amigos, pelas contribuições, sugestões, encaminhamentos
e parcerias não apenas relativas aos estudos desta tese, mas por toda a troca de
experiências que muito contribuiu para o meu desenvolvimento profissional. Sinto
muito orgulho de fazer parte deste grupo.
À equipe da Clinica de Medicina do Exercício (CLINIMEX), médicos,
profissionais de educação física, enfermagem e recepção, pela solicitude e eficiência
que muito me ajudaram nos diversos momentos coleta de dados.
A todos os pacientes que concordaram em participar dos estudos que
compõe esta tese.

10
 Aos diversos parceiros que me ajudaram na condução das pesquisas ao
longo destes quatro anos, cada um em sua área de expertise contribuindo para que
este tema de estudo, notadamente interdisciplinar, pudesse se desenvolver: Raphael
Marques Gomes, Andrea Camaz Deslandes, Claudio Gil Soares de Araújo, Gastão
Luiz Soares-Filho, Maria Cristina Ferreira, Georg H Eifert, Pedro Simões, Rafael
Freire, Marina Mochcovitch, Claudia Lucia Barros de Castro e João Felipe Franca.
Aos doutores Isabela Nascimento e Bernard Rangé pelas inúmeras e valiosas
contribuições ao trabalho por ocasião do exame de qualificação.
Aos professores doutores Antonio Egidio Nardi, Andrea Camaz Deslandes,
Angela Josefina Donato Oliva, Claudio Domenico Schettino, Ivan Figueira e Marcele
Regine de Carvalho, por aceitarem o convite para compor a banca avaliadora desta
tese. Fico muito honrada em poder contar com a presença e as contribuições de
profissionais notadamente destacados em suas áreas de atuação para o
aprimoramento do meu trabalho.
Aos meus amigos e familiares, em especial meus pais, Claudio e Denise,
minha irmã, Claudia, e minha avó, Dalva, por todo o apoio, pela torcida e pela
compreensão nos momentos de ausência e mau-humor, necessários para a
conclusão desta etapa.
Ao meu marido Gil, parceiro incondicional, por encher a minha vida de
felicidade, amor e significado.

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Apresentação

Ao iniciar meus estudos em Terapia Cognitivo Comportamental (TCC), ainda

durante a graduação, os primeiros contatos foram com pacientes com Transtorno de
Pânico. Desde o início, uma questão me intrigava: como podemos afirmar, com
segurança, como psicólogos, que os sintomas físicos experimentados pelos
pacientes durante os ataques de pânico são apenas desconfortáveis e não
necessariamente perigosos? Nenhuma das minhas leituras, tampouco a experiência
dos meus mestres, conseguiu me fornecer uma resposta definitiva para esta
pergunta. Percebi também que, se uma das questões-chave para o
desencadeamento da ansiedade nos pacientes é a baixa tolerância à incerteza
quanto a essa questão, precisávamos pensar em formas de aprimorar a abordagem
do risco representado pelos sintomas físicos para o paciente no contexto da TCC.
Durante os anos do mestrado, no Laboratório de Pânico e Respiração, estudei a
interface entre doenças respiratórias (1), vestibulares (2) e cardiovasculares (3) em
pacientes com TP e descobri que havia realmente, em especial no tocante ao
sistema cardiovascular, um risco aumentado em pacientes com TP, tanto para o
desenvolvimento quanto para o agravamento de doenças cardíacas preexistentes.
Passei, então, a me interessar especialmente por formas de abordar a existência do
risco cardiovascular em pacientes com TP no âmbito da psicoterapia, o impacto da
ansiedade relacionada à saúde em pacientes cardiopatas e em como minimizá-lo
através de mudanças comportamentais relacionadas a estilo de vida. Nesse
contexto, surgiram dois grandes temas de estudo para o doutorado: o impacto da
ansiedade no risco cardiovascular de pacientes com e sem doença coronariana e a
possível eficácia dos exercícios físicos como estratégia complementar ao tratamento
convencional do TP.
Dessa forma, esta tese é composta por uma compilação de estudos já
publicados, e outros ainda em fase de publicação, realizados por mim ao longo do
curso de doutorado. Os dois primeiros artigos são revisões sistemáticas da literatura
acerca do papel da ansiedade no risco, prognóstico e tratamento cardiovascular e
sua abordagem no contexto da TCC (4); bem como da relação entre ansiedade e
Síndome Metabólica (5).

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 O terceiro artigo relata as três fases dos estudos psicométricos de validação de
um instrumento para medir a ansiedade cardíaca, o Questionário de Ansiedade
Cardíaca (QAC) (6), traduzido e adaptado para o Português durante o mestrado (7).
Este trabalho encontra-se em fase final de publicação nos Arquivos Brasileiros de
Cardiologia e apresenta a versão brasileira definitiva do instrumento, validado para
uso em pacientes cardiopatas.
Os artigos quatro e cinco são estudos transversais da prevalência de transtornos
psiquiátricos e de diversos aspectos da ansiedade relacionada à saúde,
especialmente a ansiedade cardíaca. Estes trabalhos buscaram estabelecer
associações entre a gravidade da doença cardíaca e a presença de comorbidades
psiquiátricas e a ansiedade relacionada à saúde (8) e comparar o comportamento
dessas variáveis em cardiopatas sedentários e participantes de um programa de
exercício físico, a fim de verificar diferenças relacionadas à prática de exercícios
regulares nesta população (9).
O sexto artigo, finalizado mas ainda não submetido para publicação, relata uma
intervenção com um protocolo de exercícios físicos, realizada em pacientes com TP,
durante 12 semanas, no Laboratório de Pânico e Respiração e compara seus
resultados, em termos de variáveis psicológicas e fisiológicas, com um grupo de
pacientes com TP deste laboratório que foi tratado apenas com a medicação
convencional. Finalmente, o último artigo desta tese relata o caso de uma paciente
com TP, tratada com medicação e psicoterapia cognitivo comportamental, em que
um protocolo de exercício aeróbico intervalado foi desenvolvido e aplicado com
sucesso para abordar especificamente a ansiedade cardíaca desta paciente (10).

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Introdução

Diagnóstico e tratamento do Transtorno de Pânico

Um ataque de pânico (AP) é caracterizado por um conjunto de manifestações
autonômicas e cognitivas de ansiedade que ocorrem de maneira súbita e na
ausência de uma ameaça identificável. De acordo com a classificação atual da
Associação Psiquiátrica Americana (DSM-V), um AP completo pode ser
diagnosticado na presença concomitante de pelo menos quatro dos seguintes
sintomas: (a) aceleração da frequência cardíaca ou sensação de batimento
desconfortável; (b) sudorese difusa ou localizada (mãos ou pés); (c) tremores finos
nas mãos ou extremidades ou difusos em todo o corpo; (d) sensação de sufocação
ou dificuldade de respirar; (e) sensação de desmaio iminente; (f) dor ou desconforto
no peito (o que leva muitas pessoas a acharem que estão tendo um ataque
cardíaco); (g) náusea ou desconforto abdominal, (h) tonteiras, instabilidade
sensação de estar com a cabeça leve, ou vazia; (i) despersonalização ou
desrealização; (j) medo de enlouquecer ou de perder o controle de si mesmo; (l)
medo de morrer; (m) alterações das sensações táteis como sensação de dormências
ou formigamento pelo corpo; (n) enrubescimento ou ondas de calor, calafrios pelo
corpo (11).
A característica essencial do Transtorno de Pânico (TP) é a presença de AP
recorrentes e inesperados, seguidos por pelo menos um mês de preocupação
persistente acerca de ter outro ataque, preocupação acerca das possíveis
implicações ou consequências dos ataques, ou uma alteração comportamental
significativa a estes relacionada (11). Alguns pacientes temem que os ataques sejam
sintomas da presença de uma doença não diagnosticada e ameaçadora à vida (por
ex., cardiopatia). Tais preocupações frequentemente estão associadas com o
desenvolvimento de um comportamento de esquiva que pode satisfazer os critérios
para Agorafobia, diagnosticando-se, neste caso, tanto o TP quanto a comorbidade
com Agorafobia. A característica essencial da Agorafobia é uma ansiedade acerca
de estar em locais ou situações das quais escapar poderia ser difícil (ou
embaraçoso) ou nas quais o auxílio pode não estar disponível na eventualidade de
ter um AP ou sintomas tipo pânico (11).

14
 Os indivíduos com TP com frequência também têm AP predispostos por
situações (associados com exposição a um ativador situacional) em que algum
disparador interno ou externo ativa o sistema do medo do paciente provocando um
AP (12). A ansiedade tipicamente leva à esquiva global de uma variedade de
situações. Alguns indivíduos são capazes de se expor às situações temidas, mas
enfrentam essas experiências com considerável temor. Frequentemente, um
indivíduo é mais capaz de enfrentar uma situação temida quando acompanhado por
alguém de confiança. A esquiva de situações pode prejudicar a capacidade do
indivíduo de frequentar o trabalho ou realizar atividades cotidianas, em especial,
aquelas relacionadas a algum estímulo ativador interno ou externo associados à
ocorrência de AP (13).
Os pacientes com TP apresentam grave sofrimento e prejuízo funcional
devido ao medo da ocorrência e das consequências dos AP. O início do transtorno é
frequentemente tardio, em torno da terceira década de vida. O TP afeta duas a três
vezes mais as mulheres do que os homens e pode atingir até 3,5% da população
durante a vida (11).
Em termos de saúde mental, a eficácia do tratamento para o TP já se
encontra bastante documentada, estando a terapêutica baseada em dois pilares
principais: psicofármacos e psicoterapia de orientação cognitivo-comportamental
(TCC) (14). A literatura confirma a eficácia da terapia medicamentosa para o TP, em
especial os inibidores seletivos da recaptação da Serotonina (ISRS), os inibidores da
recaptação de Serotonina e Noradrenalina (IRSN) e os benzodiazepínicos (15-17).
No entanto, os níveis de sucesso terapêutico ainda precisam ser aprimorados, uma
vez que muitos pacientes permanecem sintomáticos quando tratados apenas com
medicamentos. Estudos demonstraram que após quatro anos de farmacoterapia,
cerca de 30% dos pacientes estão assintomáticos, 40-50% estão melhores, mas
ainda sintomáticos, e 20-30% permanecem iguais ou piores (18, 19).
A Terapia Cognitivo-Comportamental (TCC) para TP apresenta boa resposta
de curto e de longo prazo tanto para manejo dos AP quanto para ansiedade
antecipatória, evitação fóbica e Agorafobia (19, 20). A TCC apresenta resultados em
curto prazo, mas o tempo necessário para que o paciente relate alívio dos sintomas
ainda é maior do que o dos psicofármacos (21, 22). A maior parte dos estudos não
aponta diferença significativa entre os resultados obtidos com um tipo ou outro de

15
tratamento e ainda com a combinação de ambos (23). A experiência clínica,
contudo, confirma a hipótese de que a combinação de tratamentos pode ser
interessante (24), na medida em que é alcançada uma redução significativa da
frequência e intensidade dos AP com os psicofármacos e que a TCC tem um papel
importante na abordagem da Agorafobia e na manutenção dos ganhos no longo
prazo, reduzindo a recorrência do transtorno e melhorando a qualidade de vida dos
pacientes (25).
De acordo com o modelo cognitivo-comportamental, os AP aparecem a partir
de interpretações distorcidas e catastróficas dos sintomas corporais. Tais
interpretações aumentam a excitação e intensificam as sensações corporais,
confirmando, desta forma, os pensamentos ansiogênicos (26). A recorrência dos AP,
através do condicionamento (27), aumenta progressivamente a sensibilidade dos
pacientes aos estímulos internos e às situações em que o ataque ocorreu, elevando
a vigilância sobre as sensações físicas (26). O medo de sofrer outro ataque e de
suas consequências produz um quadro de ansiedade antecipatória, aumentando a
probabilidade de ocorrência de interpretações catastróficas dos sintomas quando
estes ocorrem. Tal comportamento condicionado pelo medo leva a que o indivíduo
evite desencadear sintomas somáticos (por exemplo: exercícios físicos) ou lugares
associados a ataques prévios (Agorafobia), limitando a funcionalidade e a qualidade
de vida (14, 28).
O tratamento com TCC no TP pressupõe a reestruturação dos pensamentos
catastróficos que potencializam os sintomas, a ansiedade antecipatória e
predispõem a esquiva (14, 20). A terapia passa pela educação do paciente de que
os sintomas experimentados são uma reação natural do organismo e que não
apresentam consequências perigosas para sua saúde (29). São também ensinadas
técnicas para lidar com a ansiedade, como o relaxamento muscular e o treino
respiratório (30). As intervenções cognitivas objetivam eliminar a hipervigilância às
manifestações corporais e corrigir interpretações e crenças distorcidas. As técnicas
de exposição interoceptiva e situacionais visam eliminar a Agorafobia. Por último, as
sessões finais são dedicadas à consolidação dos ganhos e à prevenção de recaídas
(14, 30).

Aspectos relevantes da psicopatologia do Transtorno de Pânico

16
 Em função de os indivíduos com TP experimentarem diferentes
manifestações de natureza autonômica durante os AP, sendo possíveis múltiplas
combinações de sintomas, cada paciente tem sua apresentação idiossincrática do
quadro. Entretanto, alguns subtipos do transtorno já foram identificados, agrupando
sintomas que comumente aparecem juntos em alguns pacientes (31), dentre os
quais o mais estudado é o subtipo respiratório do TP (32). Uma característica
comum a todos os subtipos, entretanto, é a ansiedade relacionada à ocorrência de
sintomas de pânico e a estímulos percebidos como ameaçadores à saúde. A
ansiedade quanto à saúde e outros conceitos relacionados podem ser considerados,
assim, fatores constituintes da psicopatologia do TP (33).
A sensibilidade à ansiedade é o medo dos sintomas decorrentes da
ansiedade, assim como a crença de que esses sintomas possam produzir danos
psicológicos, físicos ou sociais. Nesse sentido, altos níveis de sensibilidade à
ansiedade promovem uma maior probabilidade de o paciente reagir de forma
ansiosa a estímulos interoceptivos decorrentes da ativação autonômica provocada
por situações de ansiedade e estresse (34). Na medida em que os indivíduos
temem ser prejudicados pelas manifestações ansiosas, sensações corporais, tais
como um coração acelerado, tonturas e falta de ar passam a ser estímulos
ansiogênicos, iniciando um ciclo que pode levar a um AP (35).
Assim, a sensibilidade à ansiedade é atualmente um fator de risco bem
estabelecido na literatura, para o desenvolvimento do TP e outros transtornos de
ansiedade. Além disso, esta parece desempenhar um papel fundamental na
patofisiologia do TP, uma vez que alterações autonômicas, naturais ou provocadas
atuam como fatores desencadeadores de ansiedade e AP (36).
Mais especificamente, a ansiedade cardíaca é um tipo de ansiedade quanto à
saúde em que as preocupações do paciente estão especificamente voltadas para o
sistema cardiovascular e para a possibilidade de ter um evento cardiovascular agudo
ou de desenvolver uma doença coronariana (37). Essa envolve ainda dois outros
fatores: comportamentos de evitação de atividades ou exercícios físicos e situações
desencadeantes de sintomas cardiovasculares percebidos como perigosos e a
hipervigilância para a ocorrência de tais sintomas (6). Pacientes com altos níveis de
ansiedade cardíaca podem experimentar sensações abruptas e recorrentes de dor
torácica, na ausência de doença física que a explique. Tais sintomas, associados à

17
preocupação significativa sobre suas potenciais consequências são desencadeantes
de comportamentos de segurança, como verificação da frequência cardíaca,
hipervigilância aos sintomas e repetidas consultas médicas (7). Estes aspectos
podem ser medidos através do Questionário de Ansiedade Cardíaca, já traduzido e
adaptado para uso na população brasileira (7).
O modelo cognitivo-comportamental proposto por Zvolensky et al. (37) para
explicar a ansiedade cardíaca destaca o papel da atenção seletivamente voltada
para os sintomas cardiovasculares e do condicionamento interoceptivo na origem de
AP com sintomas limitados (somente sintomas cardiorrespiratórios) e da dor torácica
aguda. A presença de tais características poderia consistir em um fator de
vulnerabilidade para o desenvolvimento da síndrome. A ansiedade cardíaca poderia
ainda potencialmente consistir em um subtipo distinto do TP, com características
específicas e estratégias particulares de tratamento, à semelhança do que ocorre
com o subtipo respiratório, mas esta hipótese precisa ser ainda verificada. É
provável ainda que a ansiedade cardíaca tenha relação com a sensibilidade à
ansiedade observada nesses pacientes.
Estudos mostram que, em função dos mecanismos cerebrais responsáveis
pela habituação (27), a sensibilidade à ansiedade e a ansiedade cardíaca ocorrem
de forma menos intensa em pessoas que rotineiramente se engajam em atividades
físicas e exercícios (38), consistindo provavelmente um fator de risco menor para o
desenvolvimento de TP e transtornos de ansiedade nessa população. Desta maneira
é possível hipotetizar que o exercício físico regular, poderia ser utilizado como uma
estratégia preventiva, e também complementar, aos tradicionais métodos de
tratamento do TP (39).

Transtorno de Pânico e sedentarismo

Apesar de o tratamento do TP do ponto de vista da saúde mental se encontrar
em estágio avançado de desenvolvimento, recentemente, foi evidenciada na
literatura a necessidade de abordar objetivamente a relação entre TP e a saúde
física, em especial, ao aumento do risco cardiovascular dos pacientes (3, 4, 40, 41).
Estudos mostram que os pacientes com TP apresentam maior risco cardiovascular
primário e secundário (41, 42) e menor adesão a tratamento cardiológico,
especialmente a reabilitação cardíaca (43). Sintomas de ansiedade e depressão são

18
fatores que atrapalham significativamente a adesão dos indivíduos a programas de
exercício (44). Para muitos pacientes com TP, a prática de exercícios físicos pode
ser uma situação ansiogênica, dada a similaridade entre a ativação autonômica
desencadeada pelo exercício e os AP. Neste sentido, é possível que as alterações
autonômicas desencadeadas pelo exercício passem a ser o fator responsável pela
esquiva fóbica a esta atividade (35). Outra consequência potencial desta estratégia
de esquiva é tornar os pacientes com TP mais expostos aos riscos de um estilo de
vida sedentário, como o desenvolvimento da Síndrome Metabólica (5).

Figura 1 - Exercícios físicos no modelo cognitivo comportamental do Transtorno de Pânico

Além disso, estudos mostram que pacientes com TP apresentaram: (a)
frequência cardíaca aumentada e reduzida variabilidade da frequência cardíaca (b)
predominância simpática no controle da frequência cardíaca, associada a um tônus
vagal diminuído (3). Segundo estudos de Oliveira et al., independente do
diagnóstico, os indivíduos que praticam exercícios aeróbicos regularmente (20
minutos de duração, pelo menos duas vezes por semana) apresentavam uma
frequência cardíaca mais baixa e um aumento do tônus vagal em relação aos que
não se exercitavam regularmente (45). A baixa variabilidade cardíaca já foi
relacionada na literatura médica ao comprometimento das funções psicológicas
autorregulatórias, incluindo uma diminuição da capacidade atencional e da
regulação emocional (46). Os resultados relativos à baixa variabilidade da frequência
cardíaca em pacientes com TP são também consistentes com as altas taxas de
morbidade e mortalidade cardiovascular encontradas nessa população (42). Dessa
forma, a prática de exercícios físicos poderia desempenhar um papel ainda mais
importante no tratamento de pacientes com TP que apresentassem doenças

19
cardiovasculares concomitantes, uma vez que pode atuar tanto na melhora da
condição médica do paciente, como em sua condição psiquiátrica (39).
No caso específico dos pacientes com TP, o baixo condicionamento físico
decorrente da evitação destas situações é um fator potencialmente agravante do
cenário clinico, uma vez que a variabilidade da frequência cardíaca em pacientes
sedentários tende a ser maior (47). Assim, um paciente com um perfil sedentário e
com níveis baixos de condição aeróbica, ao realizar uma atividade física de
intensidade relativamente baixa em seu cotidiano, como subir um lance de escada,
possivelmente vai experimentar um aumento mais acentuado ou desproporcional da
frequência cardíaca que, percebida por um sistema do medo hipersensível, pode
desencadear ansiedade e consequentemente, mais sintomas autonômicos, talvez
até um AP (10).
É possível também, que indivíduos sedentários sejam ainda mais sensíveis a
alterações autonômicas provocadas por esforço físico cotidiano, contribuindo para a
manutenção do transtorno (39). Essa hipótese é fortalecida pelas evidências da
literatura que sugerem que alterações da função autonômica contribuem para a
fisiopatologia do TP (46). Sabe-se também que a prática de exercícios físicos pode
alterar o padrão de resposta do sistema nervoso autônomo (47). Essa alteração
seria, inclusive, considerada um dos fatores responsáveis pela indicação da prática
de exercícios com o objetivo de controlar doenças, em especial as doenças
cardiovasculares.

Exercícios físicos no contexto da Terapia Cognitivo Comportamental

A conceituação anteriormente exposta acerca do papel dos exercícios físicos
no modelo cognitivo do TP permite aventar que a hipersensibilidade aos sintomas de
ansiedade poderia ser tratada, dentro do contexto da TCC, utilizando a prática
supervisionada de exercícios físicos como uma ferramenta de dessensibilização por
exposição interoceptiva, de modo a promover habituação aos sintomas físicos (39,
48, 49). Atualmente, a exposição do paciente a sintomas físicos associados à
ativação autonômica experimentada durante episódios de ansiedade e AP
(exposição interoceptiva), é considerada elemento fundamental do tratamento do TP
de orientação cognitivo comportamental (34). A prática da exposição interoceptiva
apresenta algumas desvantagens, uma vez que é um procedimento aversivo para os

20
pacientes, além de exigir do terapeuta uma estrutura do espaço físico do consultório
que favoreça tal prática (39).
A maior parte dos terapeutas orienta seus pacientes a praticarem os
exercícios de exposição interoceptiva em locais improvisados, como o próprio
consultório, em casa ou subindo as escadas do prédio, por exemplo (34). Entretanto,
pacientes com doenças cardiovasculares, respiratórias e vestibulares, entre outras,
podem não ter indicação para a prática das exposições sem supervisão médica, em
função de serem procedimentos que ativam o sistema nervoso autônomo do
paciente, o que pode desencadear ou agravar a condição médica pré-existente (1-
3), o que deixa o terapeuta em posição delicada e prejudica o progresso e a eficácia
do tratamento.
Exercícios físicos, especialmente exercícios aeróbicos como correr, pedalar,
nadar ou caminhar, são uma das formas possíveis de evocar tais sintomas de
ativação autonômica. Entretanto, ainda assim, talvez a postura mais segura do ponto
de vista médico seja encaminhar os pacientes para programas de exercício
supervisionados ou para uma avaliação médica antes do início da prática (48, 49).
Outra vantagem importante da prática supervisionada concerne à psicopatologia da
ansiedade. Uma vez que a sessão de exercício nestes casos funcionaria como uma
exposição interoceptiva, é possível que os pacientes empreguem uma série de
estratégias evitativas e comportamentos de segurança que poderiam potencialmente
comprometer a eficácia da intervenção. Nesses casos, uma opção é a estar
acompanhado por um terapeuta ou acompanhante treinado no modelo cognitivo-
comportamental (48). A possibilidade de os profissionais de saúde mental lançarem
mão do encaminhamento para exercício físico supervisionado como ferramenta em
sua prática clínica poderia, assim, potencializar os resultados do tratamento do TP
nesses casos.
No contexto da TCC, a prescrição de exercícios pode ter um impacto indireto
também nos aspectos cognitivos relacionados TP, como a ansiedade cardíaca, a
sensibilidade à ansiedade, permitindo, a partir da exposição, a reestruturação de
crenças relacionadas à vulnerabilidade/fragilidade do organismo (10, 39). Pode-se
hipotetizar sobre a ocorrência de um possível efeito indireto também nos aspectos
comportamentais do TP, principalmente relacionados aos comportamentos de
segurança e à esquiva fóbica. Contudo, é possível que a intervenção cognitiva e as

21
exposições situacionais paralelas à prática de exercícios sejam necessárias para
alcançar tais efeitos (10).
Dessa forma, o objetivo dos estudos que compõem esta tese foi levantar as
relações entre transtorno de pânico e risco cardiovascular e propor a utilização dos
exercícios físicos, em conjunto com a terapêutica já estabelecida para o tratamento
do TP, como intervenção possivelmente útil tanto para a redução dos sintomas de
ansiedade quanto do risco cardiovascular primário e secundário dos pacientes.

22
Artigo 1:

Sardinha A, Araujo CGS, Soares-Filho GL, Nardi AE. Anxiety, panic disorder and
coronary artery disease: issues concerning physical exercise and cognitive
behavioral therapy. Expert Rev Cardiovasc Ther. 2011; 9(2):165-75.

23

Aline Sardinha†1,2,
Claudio Gil S Araújo3,
Gastão Luis Fonseca
Soares-Filho1,4 and
Antonio Egidio Nardi1
1
Laboratory of Panic and Respiration
– Psychiatry Institute – Federal
University of Rio de Janeiro
(IPUB/UFRJ), National Institute for
Translational Medicine (INCT-TM,
CNPq), Rio de Janeiro, Brazil
2
Rua Visconde de Pirajá 142/sala 1405,
Ipanema, Rio de Janeiro, CEP,
22410-000, Brazil
3
Clinics of Exercise Medicine, Clinimex
and Gama Filho University,
Rio de Janeiro, Brazil
4
Pró-Cardíaco Hospital, Rio de Janeiro,
Brazil
†
Author for correspondence:
Tel.: +55 219 417 2708
alinesardinhapsi@gmail.com
www.expert-reviews.com
Perspective
Anxiety, panic disorder and
coronary artery disease:
issues concerning physical
exercise and cognitive
behavioral therapy
Expert Rev. Cardiovasc. Ther. 9(2), 165–175 (2011)
Psychological factors such as stress and depression have already been established as primary
and secondary cardiovascular risk factors. More recently, the role of anxiety in increasing cardiac
risk has also been studied. The underlying mechanisms of increased cardiac risk in panic disorder
patients seem to reflect the direct and indirect effects of autonomic dysfunction, as well as
behavioral risk factors associated with an unhealthy lifestyle. Implications of the comorbidity
between panic and cardiovascular disease include higher morbidity, functional deficits, increased
cardiovascular risk, and poor adherence to cardiac rehabilitation or exercise programs. This
article probes the most recent evidence on the association between coronary artery disease,
anxiety and panic disorder, and discusses the potential role of incorporating regular physical
exercise and cognitive behavioral therapy in the treatment of this condition.
Keywords : anxiety • anxiety sensitivity • behavioral risk factors • cardiac rehabilitation • cognitive behavioral
therapy • coronary artery disease • exercise • panic • psychological factors
Panic disorder (PD) is one of a number of anxi- trigger a PA in a more adaptive fashion, in order
ety disorders as described in the Diagnostic not to fear somatic arousal. More recently, aero-
and Statistical Manual of Mental Disorders bic exercise training has been associated with
(DSM)-IV (Text Revision) that is characterized improvement of symptoms in PD patients and
by frequent panic attacks (PAs) [1] . Patients who acute antipanic effect in patients [7–9] and con-
suffer from PD present significant global func- trol subjects [10] . Despite the scarce investigation
tioning deficits and psychological problems  [2] , on this field until recently, it is now starting to
a greater incidence of psychiatric disorders, be considered as a useful tool in the treatment
suicidal ideation, psychological stress, activity of PD.
restrictions and chronic physical diseases, and Anxiety has recently received special atten-
poorer indices of physical and mental health [3,4] . tion as a potential risk and aggravation factor for
Patients who present an association between cardiovascular diseases, notably in terms of the
panic and physical diseases experience more interface between the autonomic changes caused
deficits in a wide range of modalities than those by chronic anxiety and PAs, and the autonomic
who suffer from only one of these conditions [5] . mechanisms of cardiac regulation  [11,12] . The
Cognitive behavioral therapy (CBT), is con- association of anxiety, particularly PD, with cor-
sidered, along with pharmacological treatment onary artery disease (CAD) may even be fatal. A
with selective serotonin reuptake inhibitor study performed in a psychiatric hospital showed
antidepressants, the gold-standard treatment that those who suffer from PD had a mortal-
for PD  [6] . The rationale for this intervention ity rate for cardiovascular causes that was two
is that patients can learn how to manage anxi- times greater than expected compared with the
ety states and symptoms, as well as reinterpret same age group, gender and time of hospitaliza-
the environmental and interoceptive cues that tion [13] . The presence of PD may be considered
10.1586/ERC.10.170 © 2011 Expert Reviews Ltd ISSN 1477-9072 165
 Perspective Sardinha, Araújo, Soares-Filho & Nardi
an independent risk factor for CAD, either as a trigger for acute
myocardial infarction (AMI) or for morbidity/mortality from
cardiovascular causes [14,15] .
Adding to that, when studying the degree of knowledge of
generalist American doctors on PD, Teng et al. stated that only
50% of the items asked were answered correctly. Only half of the
professionals knew the definition of a PA or its clinical charac-
teristics and treatment methods. Concerning CBT, only 32% of
the sample knew that this is the treatment of choice for PD [16] .
King et al. highlight that failure in the identification of somatic
symptoms associated with PD during primary care result in costly
and unnecessary diagnostic procedures [17] . Information on the
association between anxiety, panic and physical diseases appear
to be deficient among both physicians and healthcare profession-
als in general, making it difficult to access adequate treatment
and aggravating the functional and physical damage of PD [16] .
Although the current focus of the literature has expanded from
the simple need to perform a differential diagnosis between PD
and CAD to now consider the possible mechanisms responsible
for their co-occurrence and the consequences of this comorbidity,
therapeutic strategies have not yet been proposed that are specifi-
cally directed at this population [18] . In addition, it is possible
that psychological variables associated with anxiety and panic
play an important role in maintaining and adhering to cardio­
vascular treatment, particularly with a structured physical exercise
program [11] . As such, the objective of this article is to present
evidence of an association between PD and CAD, and to pro-
pose nonpharmacological therapeutic strategies for these patients,
combining the regular practice of physical exercise with CBT.
Methods
We performed a systemic review of the literature, consisting of
a retrospective search of scientific articles. An initial electronic
search was performed for scientific articles in the databases
PubMed/Medline and ISI/Web of Science using the following
keywords: ‘panic’, ‘anxiety’, ‘coronary artery disease’, ‘exercise’ and
‘physical activity’. The criteria used in the selection of articles for
review were the type of study design (clinical study or controlled
clinical study) and relevance to the focus of the present discussion.
An additional search was further performed based on the refer-
ences cited in the selected articles. Given that the proposed focus of
this work was on the current evidence, the most recent article was
used in the case of duplicate information. Analysis of the results
was performed in two ways: controlled studies were systematically
accounted for, whereas the studies with methodological designs
that had less power of evidence were used for the discussion and
proposition of therapeutic strategies.
Results
Evidence is available concerning anxiety and PD as a primary car-
diac risk factor for healthy persons without CAD [19] , and as a sec-
ondary or tertiary risk factor in patients with various clinical CAD
conditions [18,20] . Various mechanisms are proposed to explain the
association between PD and CAD. There have been a number
of studies of exercise and anxiety, although few specifically with
166
anxiety disorders. On the other hand, no clinical study was found
that focused on the impact of a program of physical exercise on the
cardiopathology of patients with PD. The benefits of physical exer-
cise and CBT over general psychological factors among patients
with cardiopathy and, more specifically, on the sensitivity to anxi-
ety – which is considered a prodromal symptom of PD – among
patients with PD, are well documented. Based on the studies that
have shown exercise-related reductions in anxious symptoms and
other studies that have shown psychological benefits of exercise,
this article raises the discussion of whether these findings could
be applied to the treatment of PD in cardiac patients in order to
reduce their secondary cardiac risk. In this article, we present
findings from which the authors propose ­interventions to reduce
the impact of panic in cardiopathic patients.
Potential mechanisms between anxiety, panic & CAD
In the past, most research efforts were focused on the association
between depression and incident CAD. Recently, anxiety has been
studied as a primary and secondary independent risk factor for CAD.
A meta-analysis performed by Roest et al. comprising 249,846 indi-
viduals demonstrated that anxiety seemed to be an independent risk
factor for incident CAD and cardiac mortality [19] . In a nationwide
survey including 49,321 young Swedish men followed for 37 years,
Janszky et al. found that multiadjusted hazard ratios for anxiety
assessed at 18 years of age were 2.17 (95% CI: 1.28–3.67) for CAD
and 2.51 (95% CI: 1.38–4.55) for AMI [21] . Despite the growing
body of research conducted in the past years, mechanisms through
which anxiety might affect CAD remain unclear [11] .
The constant activation of the hypothalamic–pituitary–adrenal
axis by chronic anxiety results in hemodynamic adjustments, such
as an increase in heart rate (HR) and blood pressure (BP), at levels
similar to those seen during physical exercise [13] . PD patients tend
to present autonomic alterations that can be expressed by predomi-
nance of sympathetic control of HR and decreased vagal tone [22] ,
resulting in an increased resting HR and reduced HR variability
(HRV). Moreover, this pattern is linked to the symptomatology of
PAs. In everyday situations, the profile would be exactly the oppo-
site [23] . In any case, only the decrease in parasympathetic activity
would not be enough to trigger PAs. Research conducted in labo-
ratory paradigms specific activation of the sympathetic nervous
system showed that patients with or without PD experienced an
increase in sympathetic activity and/or vagal withdrawal, leading
to a relative sympathetic predominance [24] . Further details on the
autonomic function in PD can be found in our previous study [11] .
Analysis of HRV has been widely used in clinical research in
attempts to understand the autonomic control of HR. HRV is a
noninvasive method of measuring the autonomic modulation of
cardiac function, and a low HRV represents an important predictor
of adverse cardiovascular events. This technique has also helped to
elucidate the underlying mechanisms of PD and the symptoms of
palpitation. There are objective data that show a relative reduction
of HRV and the vagal tone in patients with PD [25] . These results
are consistent with the cardiac symptoms experienced during PAs.
On the other hand, the findings of low HRV contrast with the high
autonomic liability found among patients with chronic anxiety.
Expert Rev. Cardiovasc. Ther. 9(2), (2011)
 Anxiety, panic disorder & coronary artery disease
This apparent contradiction is found when considering traditional
models of homeostasis, in contrast with the more modern perspec-
tive of organismic regulation, which considers the capacity of physi-
ological variability as essential to the stability of the organism [25] .
Consistent with this vision are the studies that relate low HRV,
which is found in both cardiopathic patients and those with PD
or anxiety related to physical symptoms (‘panic-like’), with an
increase in cardiac risk [26] . PD and CAD frequently co-occur,
making diagnostic differentiation particularly complex, and such
patients frequently present greater cardiovascular morbidity and
mortality than patients with cardiopathy but without PD [18] .
However, the underlying mechanisms of this association are still
unknown, and the hypothesis of autonomic dysfunction is cur-
rently one of the most studied to explain this association [26] . In
contrast to this hypothesis, the results of Lavoie et al. suggest that,
contrary to what is observed in noncardiopathy patients with PD
and in patients with CAD but without PD, individuals with both
CAD and PD appear to present greater sympathetic modulation
during daily activities [27] . Even though such data are preliminary,
this evidence suggests that the changes in HRV may not be the
only or main primary mechanism responsible for the poorer car-
diovascular prognosis of patients with both cardio­vascular patholo-
gies and PD [27] . More recently, it has been hypothesized that the
observed association between anxiety disorders with significantly
lower HRV can be even driven by the effects of antidepressants [28] .
Autonomic dysfunctions may also be involved in the association
found among BP, PAs and PD. Davies et al. have hypothesized
that symptoms of panic of autonomic origin are more common
in the PA experienced by hypertensive individuals than those who
are normotensive. As such, there would be a grouping of auto-
nomic symptoms of panic that could act as a distinct factor in the
presentation of PD among these patients. These findings suggest
autonomic dysfunction as a potential link between hypertension
and panic [29] . Another important observation was the increase of
low-density lipoprotein cholesterol in patients with anxiety disor-
ders reported by Peter et al. [30] . It is possible that the autonomic
dysfunction of the heart has an indirect role in the relationship
between panic and CAD through a reduction in HRV [31,32] and
the possible association with other cardiovascular risk factors,
such as ­hypercholesterolemia and hypertension [29] .
A third possible explanation of the association between PD
and CAD involves lifestyle and its impact on cardiovascular risk
factors. Psychological disorders are independently associated with
habits of risk, such as tobacco use, alcohol use, a sedentary lifestyle
and low adherence to therapeutic programs. Thus, the treatment
of these psychological conditions may have an indirectly beneficial
impact over lifestyle as well as over the decrease in cardiovascu-
lar risk factors. Cognitive behavioral interventions that aim not
only at reducing emotional stress but which are also focused on
motivational interventions to unhealthy behavior modification
and changing the patient’s lifestyle may be quite beneficial for
this type of patient [33] .
Psychological stress in general is known to increase the inci-
dence of sudden cardiac death. More recently, the acute impact
of negative emotions in the development of arrhythmias and their
www.expert-reviews.com
Perspective
role in cases of sudden death of cardiovascular origin have been
the subject of scientific interest [34,35] . Although Lampert et al.
found that, in patients with implantable cardioverter-defibrilla-
tors ventricular arrhythmias were significantly triggered by anger
states but not by anxiety, it is plausible that anger and other strong
emotions can trigger polymorphic, potentially life-threatening
ventricular arrhythmias in vulnerable patients [36] . Autonomic
changes including increased sympathetic activity and vagal with-
drawal may lead to increases in heterogeneity of repolarization
that can be associated with arrhythmogenesis, as well as increasing
inducibility of arrhythmia [37] .
In addition, in the last decade there have been reports of a car-
diac syndrome that is associated with anxiety known as tako-tsubo
cardiomyopathy. This condition is also known as broken heart
syndrome [38] and is characterized by:
• Thoracic pain and changes in the ECG mimicking AMI;
• Minimal elevation of myocardial enzymes;
• The absence of significant obstructions in the coronary angio­
graphy associated with reversible changes in motility of the left
ventricle [39] ;
• Favorable prognosis [40] .
The most interesting aspect of this cardiomyopathy is that it is
usually preceded by severe emotional or physical stress [38] .
Despite the long-term association between PD and cardiovas-
cular mortality, reports were found of patients with PD who
presented angina and cardiac ischemia during a PA. Two of
these patients progressed to develop AMI. As no patient pre-
sented a significant obstruction in the coronary angiography, the
mechanism that led to the AMI was attributed by the authors to
spasms of the coronary arteries. Such cases demonstrate that the
typical angina during a PA, even in patients with no CAD, may
have an organic cause and may be potentially dangerous  [41] .
Biyik et  al. also report another case of a young 35‑year-old
individual who had an AMI after getting into a fight, though
tests did not show any indication of obstruction or coronary
malformation [42] .
Symptom differentiation between PD & CAD
The differential diagnosis between psychogenic and cardiac ori-
gins for thoracic pain is currently one of the greatest challenges
of outpatient and emergency services. A diagnosis of PD is rarely
reached and this ‘blind’ diagnosis may lead to a delay in treatment
of PD and a consequent chronicity of the symptoms, limiting
activities and quality of life in addition to triggering the excessive
and inappropriate use of medical resources, including an inherent
risk for the performance of invasive or noninvasive procedures and
a considerable expenditure of financial resources.
Angina with both typical and atypical presentations is a fre-
quent complaint during PAs. Patients with PD who present
thoracic pain typically use health services and present more
discomfort, anguish and phobic avoidance [43] . However, Fleet
et al. observed that these characteristics of patients with CAD
and PD are not different from the behavior of individuals without
167
 Perspective Sardinha, Araújo, Soares-Filho & Nardi
CAD but with PD, and that the psychological symptoms of these
patients appear to be more strongly related to the presence of PD
than to the cardiovascular diagnosis [44] .
Studies performed in emergency departments with consecu-
tive patients presenting thoracic pain upon arrival revealed that
a diagnosis of PD or another mental disorder as cause of tho-
racic pain was made in only 2–3% of cases [44,45] , indicating
an increased clinical insensitivity to the correct diagnosis. In
another study, Fleet et al. verified that the reports of the preva-
lence of PD in cardiological services vary between 10 and 50%,
illustrating the differences in criteria among professionals in this
context [46] . This lack of consensus on the actual prevalence of
PD among CAD patients might also be a byproduct of a bias
caused by the fact that both PD and CAD independently con-
tribute to cardiological health service use, which can artificially
inflate the rates of comorbidity between PD and CAD found in
these settings compared with nonclinical samples (i.e., Berkson’s
bias [47]).
In spite of the relatively high risk that a patient with thoracic
pain other than angina will have PD (relative risk: 2.03; 95% CI:
1.41–2.92), Katerndahl warns that 13% of individuals who
arrive at cardiological emergencies with typical pain also present
PD [43] . On the other hand, to further complicate the frame-
work, it is important to remember that a substantial number of
patients suffering from cardiovascular pathologies do not present
thoracic pain.
Thus, the type of pain alone may not be considered a good
instrument for differentiation between these two conditions.
Regardless, the association between CAD and PD appears to
be more common among patients who present atypical pain and
symptoms that cannot be completely explained by the coronary
clinical presentation [46] . A main cause of this diagnostic difficulty
may be the fact that emergency care professionals understandably
prioritize the differentiation between PD and CAD to facilitate an
early diagnosis of acute coronary syndrome and other conditions
that are a serious threat to life; thus, they often do not observe
the possibility of co-occurrence. The use of protocols to trace the
disorders of anxiety and depression in a cardiologic emergency
could minimize this diagnostic difficulty. A study performed in a
thoracic pain unit showed that among those patients with thoracic
pain of an undetermined cause, the use of a Hospital Anxiety and
Depression Scale (HADS) allowed anxiety and depression to be
diagnosed in 53 and 25% of the cases, respectively [48] .
Comorbidity between PD & CAD
Given the negative influence of PD on the cardiovascular prog-
nosis, Katerndahl warns that there is a need to track both the
patients with CAD for the existence of comorbidity with PD and
the patients with PD for the presence of coronary lesions [49] . Fleet
et al. add that PD may be more prevalent in patients with CAD
whose cardiovascular diagnosis took longer to be performed, gen-
erating a period of insecurity between the time of the onset of
symptoms and the final diagnosis [44] . It is possible that nonadap-
tive beliefs regarding the cardiovascular condition, especially with
respect to the occurrence of typical angina and thoracic pain in
168
general, may have a negative impact on the functioning of these
patients, a phenomenon that should be systematically investigated
and restructured [50] .
An original study performed in patients with stable CAD who
also suffered from PD showed interesting results of inducing panic
through the inhalation of CO2 at 35% and then following the
patients’ progression using myocardial scintigraphy. The patients
with PD who exhibited PAs triggered by the CO2 showed signifi-
cantly more reversible deficiencies of blood perfusion than did the
controls with CAD but without PD. As such, even when cardio-
vascular stabilization was achieved, with regular use of medication
the occurrence of PAs in individuals with CAD appears to be
potentially dangerous [51] .
CBT contributions to the treatment of PD in
cardiac patients
Despite the efficacy of psychopharmacological treatment in reduc-
ing PAs, many patients fail to respond adequately to these inter-
ventions. The effect size for therapeutic response ranges between
0.6 and 2.3, depending on the dimension being evaluated [52,53] .
CBT provides an alternative and efficacious method for treat-
ing PD and agoraphobic avoidance, and can be used as first-line
therapy for PD [6,54] . CBT presents good short- and long-term
response for core panic symptoms as well as anticipatory anxiety,
phobic avoidance and agoraphobia [2] .
According to cognitive behavioral models, PAs arise from
distorted and catastrophic interpretations of bodily symptoms.
Such interpretations increase arousal and intensify bodily sensa-
tions, generating more catastrophic interpretations and anxiety
in a rapid spiral that leads to panic. Repetition of attacks make
individuals increasingly more sensitive to internal stimuli and to
situations in which they occur, and to heighten surveillance of any
physical sensation. Combined with that is anticipatory anxiety and
catastrophic interpretations of symptoms. Such fear-conditioned
behavior leads the individual to avoid somatic symptoms or places
associated with previous attacks. The main goals of CBT are cor-
recting catastrophic interpretations, providing anxiety coping
strategies and extinguishing conditioned fears of body sensations
(interoceptive exposure techniques) and avoidances [2] .
A study using qualitative methods demonstrated that patients
without a psychiatric diagnosis subjected to a cardiac transplant
adhered to a more active lifestyle than did patients with PD who did
not have cardiac problems [55] . High anxiety and depression scores
are factors that significantly hinder the adherence of patients to regu-
lar physical exercise programs [56,57] . Cardiac rehabilitation programs
that include physical exercise may represent an additional challenge
for patients with CAD and PD or anxiety related to physical symp-
toms [56,58] . Individuals with PD or those who are sensitive to anxiety
– who fear somatic arousal – would be more sensitive to interoceptive
stimuli, leading autonomic alterations, whether natural or provoked,
to transform into factors that trigger anxiety and PAs  [59] . In this
sense, it is possible that the autonomic alterations triggered by physi-
cal exercise become the factor responsible for the phobic avoidance
of this activity [11,60] . It is even possible that reduced aerobic fitness
might contribute to the pathophysiology of PD [61] .
Expert Rev. Cardiovasc. Ther. 9(2), (2011)
 Anxiety, panic disorder & coronary artery disease
One factor to be considered in the study of the impact of psy-
chological symptoms over the maintenance of cardiovascular
treatment is what is known as cardiac anxiety [62] . Cardiac anxiety
is a condition characterized by abrupt and recurrent sensations
of thoracic pain, without a physical disease to explain it, that
are associated with significant concern over its potential conse-
quences. This symptom is also associated with safety behaviors,
such as verification of the HR, hypervigilance of symptoms and
repeated medical consultations [63] .
The cognitive behavioral model proposed by Zvolensky et al. to
explain cardiac anxiety highlights the role of selective attention
focused on cardiovascular symptoms and of interoceptive condi-
tioning in the origin of PAs with limited symptoms (only cardio-
respiratory symptoms and acute thoracic pain) [64] . The presence
of such characteristics could predispose susceptible ­individuals to
the development of the syndrome.
There is considerable evidence implicating heartbeat perception
accuracy and anxiety sensitivity in the development of panic in
adults and children, as increased panic/somatic symptoms are
associated with an enhanced ability to perceive internal physi-
ological cues and fear of such sensations [65,66] . Ehlers et al. found
that patients who seek medical help for benign palpitations can be
distinguished from those with clinically significant arrhythmias
[67] . Individuals with awareness of sinus rhythm could be distin-
guished from those with arrhythmia by several variables: female
sex, higher prevalence of PD, higher HRs, lower levels of physi-
cal activity, fear of bodily sensations and depression. By contrast,
patients with arrhythmias rarely reported palpitations and were
more likely to perceive their heartbeats accurately than patients
with sinus rhythm and control subjects. In fact, there is evidence of
differential effects of anxiety sensitivity and heart-focused anxiety
as a function of gender, with higher prevalence of heart-focused
anxiety in women.
Cardiac anxiety could potentially be a distinct subtype of PA,
with specific characteristics and treatment strategies compa-
rable with those that occur with respiratory subtype, although
this hypothesis still needs to be verified. It is probable that car-
diac anxiety is related to the sensitivity to anxiety observed in
these patients.
Exercise intervention for anxiety & panic in
CAD patients
There is a growing body of evidence pointing to the potential
benefits of aerobic exercise as an adjunct tool in the treatment of
anxiety and PD (Table 1) . Broocks et al. compared the therapeutic
effect of a 10‑week running program for patients with PD to a
drug treatment with clomipramine and to placebo, and found that
regular aerobic exercise alone is associated with significant clini-
cal improvement in patients suffering from PD, in comparison
to placebo, but that it was less effective than treatment with clo-
mipramine [7] . Later, the same authors associated aerobic exercise
with paroxetine, and found that while paroxetine was superior to
placebo, aerobic exercise did not differ from relaxation training
in most efficacy measures [68] . It is possible that, although run-
ning exposes patients to the internal feared cues of palpitations,
www.expert-reviews.com
Perspective
sweating, rapid breathing and so on induced by exercise, it may
not induce exposure to all of the cues that PD sufferers fear in the
manner required for optimum outcome.
Conversely, Smits et al. demonstrated that participation in a
treadmill exercise program for 2 weeks is effective in reducing
sensitivity to anxiety, even without concomitant physiothera­
peutic interventions [56] , suggesting that supervised exercise may
be prescribed as an intervention in addition to CBT for patients
with PD, based on the observation that sensitivity to anxiety
appears to play a fundamental role in the physiopathology of PD.
This recommendation has been recently tested and has shown
encouraging results, also with brief interventions (six sessions) [69]
and low-intensity exercises such as walking [9] .
Other results have shown that regular physical exercise creates an
acute antipanic effect among healthy individuals subjected to situ-
ations that induce symptoms of panic, such as inhalation of CO2
at 35% [70] . It could be hypothesized that, although the autonomic
symptoms may be exacerbated in these individuals, possibly from
the interoceptive conditioning that has already been established, the
impact of exercise on the sensitivity to anxiety may be beneficial.
This would allow individuals with PD to be exposed to situations of
autonomic activation that could function as interoceptive exposure,
in turn contributing to the extinction of the interoceptive condi-
tioning, present with PD, that lead these individuals to associate
somatic arousal and normal physiological variations with fear.
The affective and anxiolytic benefits associated with aerobic
exercise are well documented. However, literature concerning resis-
tance exercise has suggested a more variable response (i.e., a short-
duration increase in state anxiety, which eventually is reduced
below baseline). Significant reductions in state anxiety following
bouts of aerobic exercise have been consistently noted, whereas
changes are generally absent or present less significance after acute
resistance training [71] , which may play an important role in the
adoption and maintenance of a resistance training program. Some
evidence was found showing that resistance training exercises may
help as an adjunct to an aerobically-oriented program as it may
improve self-esteem and confidence, and could have an indepen-
dent impact on anxiety in healthy controls [72,73] . Hale et al. found
that combined sessions of aerobic and resistance exercise are associ-
ated with reductions in state anxiety, and that the order in which
the exercise is completed does not influence this response [74] .
No study was found using resistance training in anxiety dis-
orders or in cardiac patients with PD, which restricts the present
discussion to an extrapolation of the available evidence showing
that exercise can be understood as a useful tool in the treatment
of panic owing to interoceptive habituation and anxiety sensitivity
reduction, and that it was applied successfully in the treatment of
CAD. Another important aspect to be noted is that the effect size
of the antipanic impact of exercise interventions might be inflated
in the presented studies due to the unimethod approach used in
the assessment of antipanic outcomes.
Physical exercise even appears exert a positive impact over the
course and prognosis of various chronic mental diseases [75] . There
is evidence that aerobic conditioning and muscle strength may be
improved by means of regular physical exercise among patients
169
 Perspective Sardinha, Araújo, Soares-Filho & Nardi

Table 1. Available evidence on the use of regular exercise in the treatment of panic disorder.
Study (year) Patients Anxiety Exercise Duration Outcome Ref.
(n) manifestation intervention
Broocks et al. 46 (exercise PD with and without Walking or running a 10 weeks Exercise was associated with [7]
(1998) group n = 16 agoraphobia 4-mile route, significant clinical improvement
and control three-times a week in PD patients but less
n = 30) effective than treatment with
clomipramine
Wedekind 75 PD with and without Running 10 weeks While paroxetine was superior to [8]
et al. (2010) agoraphobia placebo, aerobic exercise did not
differ from relaxation training in
most efficacy measures
Merom et al. 74 PD, generalized anxiety 30-min sessions of 10 weeks Exercise plus CBT was more [9]
(2008) disorder or social moderate-intensity effective that CBT alone in reducing
phobia walking (150 min per scores in self-report depression,
week) anxiety and stress scales
Esquivel et al. 18 PD patients submitted Moderate/hard Acute Panic reactions to CO2 were smaller [88]
(2008) to a panic induction exercise or very light intervention in patients that performed
maneuver with exercise moderate/hard exercise in contrast
35% CO2 with those that performed very
light exercise
Ströhle et al. 24 PD patients vs healthy Aerobic treadmill Acute Compared with healthy control [87]
(2010) controls exercise (30 min at intervention subjects, patients with PD had
an intensity of 70% significantly reduced BDNF
of the maximal concentrations at baseline and
oxygen uptake) 30 min of exercise significantly
increased BDNF concentrations only
in these patients
Ströhle et al. 24 PD patients vs healthy Aerobic treadmill Acute Patients with PD showed increased [90]
(2009) controls submitted to a exercise (30 min at intervention somatic but not anxiety symptoms
panic-induction an intensity of 70% after exercise. Exercise reduced the
maneuver with CCK-4 of the maximal severity of CCK-4-induced panic
oxygen uptake) and anxiety
Esquivel et al. 20 Healthy subjects Aerobic exercise in a Acute Subjects under the exercise [91]
(2002) submitted to a bicycle ergometer intervention condition reported fewer panic
panic-induction reaching >6 mm of symptoms than controls after a
maneuver with 35% blood lactate CO2 challenge
CO2
Ströhle et al. 15 Healthy subjects Aerobic treadmill Acute Panic attacks occurred in 12 subjects [10]
(2005) submitted to a exercise (30 min at intervention after rest but in only six subjects
panic-induction an intensity of 70% after exercise
maneuver with CCK-4 of the maximal
oxygen uptake)
BDNF: Brain-derived neurotrophic factor; CBT: Cognitive–behavioral therapy; CCK: Cholecystokinin tetrapeptide; PD: Panic disorder.

with chronic diseases without the occurrence of significant side
effects [76] . Exercise improves the prognosis of these patients and
reduces their risk of mortality, making it possible to reasonably
add a few more years to their life expectancy [77] . In addition,
patients with countless other clinical conditions related to panic,
such as respiratory [78] and vestibular [79] dysfunctions, may benefit
from the regular practice of physical exercise, possibly resulting in
an improvement in the psychiatric and cardiovascular prognoses.
Patients undergoing 4 months of aerobic exercise and stress con-
trol based on CBT obtained better control over CAD and stress
compared with those patients treated with medication alone [80] .
The data on the practice of exercise in patients with PD allow us
to consider that the sensitivity to the symptoms of anxiety could
be treated within the context of CBT, using the supervised prac-
tice of physical exercises as a desensitization tool for interoceptive
exposure. It is plausible that the exercise intervention might be
more effective in achieving even more symptom improvement if
it was conducted as a systematic interoceptive exposure tool in the
context of CBT, tailored to involve all of the patients’ feared cues
systematically rather than just incidental to the exercise sched-
ule. In this sense, if the experience of exercise were accompa-
nied by cognitive restructuring, it could be as effective as regular

170 Expert Rev. Cardiovasc. Ther. 9(2), (2011)

 Anxiety, panic disorder & coronary artery disease Perspective

interoceptive exposure therapy but with

other potential benefits, specially cardiac Clinical condition Physiological background Intervention
risk reduction [81] . Therefore, it would be
possible to reduce both sensitivity to anxi-
Regular physical
ety and cardiac anxiety to favor lifestyle Autonomic exercise
changes, reducing behavioral risk factors dysfunction
and facilitating the adhesion to cardiac
rehabilitation programs [82] . Myocardial O2
Panic disorder supply–demand Antipanic effect
+ imbalance Higher
Expert commentary adherence
Coronary artery
Some evidence suggests that acute anxiety Antidepressant effect
disease
and panic, as well as stress and depres- Lower phobic
Anxiolytic effect
sion, should be regarded as risk factors that avoidance
should be addressed for both the preven- Interoceptive habituation
tion and treatment of cardiovascular dis-
eases [83] . It has become important to under- Psychological Cognitive behavioral
stand the nature of the mechanisms of this factors therapy
relationship to allow for the development of
efficient therapeutic strategies. Therapists Figure 1. Role of exercise and cognitive behavioral therapy interventions in
should be alert in their practice to the possi- ­patients with panic disorder and coronary artery disease.
bility that their patients with PD also suffer
from other physical diseases that may be related to the presented In therapeutic terms, our research and that of other groups has
symptoms, notably CAD. We cannot lose site of the fact that it is been dedicated to studying the antipanic effect of exercise among
possible that the symptoms experienced by the patients are really patients who suffer from anxiety disorders, and yet other groups
indicators of a physical condition that needs to be treated. have studied the impact of exercise programs on the remission
We suggest, based on the aforementioned data, the systematic of PD. Although the anxiolytic and antipanic effects of exercise
prescription of supervised physical exercise for patients who suf- have already been empirically observed, the mechanisms of action
fer from anxiety, PA, and PD, especially those who also suffer involved remain to be elucidated. Current studies have centered on
from CAD, given the benefits of the regular practice of physical mechanisms related to the brain-derived neurotrophic factor [87]
exercise for both conditions. Furthermore, it is important that the and the serotonergic system [88,89] .
treatment for PD, mainly in patients with CAD or other cardiac Therefore, despite the clear association between anxiety and
risk factors, include approaches that are specifically directed at cardiovascular diseases and the beneficial impact of exercise over
the remission of PAs and the reduction of cardiovascular risk fac- both cardiovascular conditions, few studies have been performed
tors associated with the patient’s lifestyle, such as CBT [84] . This to find guidelines for the prescription of physical exercise as an
pyschological approach, as occurs in other mental diseases such as additional treatment for patients with anxiety that is comorbid
bipolar disorder [85] , appears to also be essential to manage the fac- with cardiac disease. More specifically, we have found no study that
tors specifically related to PD in patients with cardiopathy that may combines psychological approaches with the practice of exercise
constitute a barrier to the adhesion to cardiovascular treatment, to reduce cardiac anxiety, sensitivity to anxiety and panic, aiming
such as sensitivity to anxiety and cardiac anxiety. In addition, it at increasing adherence of anxious cardiopathy patients to cardiac
is necessary to identify and treat the presence of such prodromal rehabilitation programs that involve exercise. As such, we hope that
symptoms of PD to prevent the development of the anxiety disor- researchers explore this topic within the next 5 years with the goal
der in patients with coronary pathology, which may be deleterious of providing empirical subsidies that enhance the clinical treatment
for the cardiovascular prognosis of these patients (Figure 1) . of patients who present a CAD and anxiety comorbidity.

Five-year view Financial & competing interests disclosure

The impact of psychological factors in the development and
aggravation of cardiovascular diseases has now been established.
Various studies also point to the impact of psychological factors
such as depression and anxiety in the abandonment of rehabili-
tation programs [57] , and have already proposed programs that
include psychological approaches, especially cognitive behavioral
techniques [86] . However, the mechanisms by which this associa-
tion occurs still need to be clarified in the coming years. Another
point to clarify is the degree to which the impact of anxiety in
CAD can be dissociated from the presence of depression.
This work was supported by the Brazilian Council for Scientific and
Technological Development (CNPq), grant 470382/2006-6, and the
National Institute for Translational Medicine (INCT-TM, CNPq). Aline
Sardinha is receiving a doctoral fellowship from CAPES. Claudio Gil Araújo
receives research support from CNPq and from Scientist of Our State – Rio
de Janeiro program (FAPERJ). The authors have no other relevant affilia-
tions or financial involvement with any organization or entity with a finan-
cial interest in or financial conflict with the subject matter or ­materials
discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

www.expert-reviews.com 171
 Perspective Sardinha, Araújo, Soares-Filho & Nardi

Key issues
• It is necessary to be attentive to the association between cardiovascular diseases and anxiety disorders, especially panic disorder.
• Cardiac patients with anxiety have greater morbidity, worse adherence to treatment and a greater risk of new coronary events than do
nonanxious coronary artery disease patients.
• Cardiac anxiety and sensitivity to anxiety are prodromal anxious manifestations of the panic disorder that should be addressed with
coronary artery disease patients to reduce potential impacts on prognosis and treatment.
• Cardiac anxiety and sensitivity to anxiety appear to be facilitators for abandoning cardiac rehabilitation programs that include
physical exercise.
• Psychological approaches such as cognitive–behavioral therapy (CBT) may act not only on the psychological factors associated with
cardiovascular diseases, such as anxiety and depression, but also in the modification of behavioral risk factors and in the potentiating of
the adhesion to cardiovascular treatment and physical exercise.
• Physical exercise appears to have an acute antipanic, antidepressive and chronic anxiolytic effect, which could be used as an additional
tool in the treatment of coronary artery disease patients with anxiety.
• We recommend a combination of CBT and a prescription of regular exercise as an adjunctive therapy in the treatment of the association
between panic disorder and cardiovascular diseases.

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Artigo 2:
Sardinha A, Nardi AE. The role of anxiety in metabolic syndrome. Expert Rev
Endocrinol Metab. 2012;7(1):63-71.

35
 Review

The role of anxiety in

metabolic syndrome
Expert Rev. Endocrinol. Metab. 7(1), 63–71 (2012)

Aline Sardinha* and
Antonio E Nardi
Institute of Psychiatry – Federal
University of Rio de Janeiro (UFRJ),
Rio de Janeiro, Brazil
and
INCT – Translational Medicine (CNPq),
Avenida Venceslau Brás, 71, Fundos,
Campus Praia Vermelha,
Rio de Janeiro, Brazil
*Author for correspondence:
alinesardinhapsi@gmail.com
Metabolic syndrome (MS) seems to be associated with both depression and increased
cardiovascular risk. This article emphasizes the most relevant findings on the link between MS
and psychological cardiovascular risk factors, focusing on the impact of anxiety. There is evidence
for an association between psychological disorders and the development of MS, which could
eventually increase cardiovascular risk. However, the coexistence of anxiety in MS patients seems
to be a byproduct of anxiety–depression comorbidity, stress and negative health behaviors.
Endocannabinoid receptors, and hypothalamic–pituitary–adrenal axis dysregulation and
sympathetic hyperactivation are the most commonly mentioned plausible underlying pathways.
Keywords : anxiety • cardiovascular risk • coronary artery disease • depression • metabolic syndrome
• psychological factors

Psychological factors are known to play a role
in cardiovascular risk by contributing sig-
nificantly to the pathogenesis, development
and aggravation of coronary artery disease
(CAD) [1] . This evidence is composed largely
of data relating increased cardiovascular risk
to five specific psychosocial domains: depres-
sion, anxiety, personality factors and character
traits, social isolation and chronic life stress [2] .
However, most research on the role of emo-
tional disturbances in cardiovascular outcome
has focused on depression. Earlier studies relat-
ing depression and CAD have highlighted the
physiological mechanisms mediating this asso-
ciation, leading to the identification of shared
genetic determinants, inflammation, blood
clotting and vascular mechanisms as plausi-
ble explanatory hypotheses [3] . Subsequently,
behavioral aspects started to be addressed, and
an indirect association with increased cardio-
vascular risk through an unhealthy lifestyle
linked to depression and stress (tobacco use,
alcohol abuse, sedentarism, obesity, and so on)
has been hypothesized [4] .
Until recently, evidence linking anxiety to
cardio­vascular risk was limited to demonstra-
tions of elevated mortality rates among psychiat-
ric patients with anxiety disorders [5] . Increasing
evidence now links anxiety to cardiac events in
the general population [2] . Additionally, anxiety
seems to predict a greater risk of major adverse
cardiac events in patients with stable CAD and
to negatively influence the development and
prognosis of CAD through hyperactivation of
the autonomic nervous system [6] .
Metabolic syndrome (MS) is a construct that
defines a closely related cluster of factors that
increase the risk of CAD and diabetes mellitus
Type 2. Although increasing research efforts
have been allocated lately in the attempt to pro-
pose a universally accepted pathogenic mecha-
nism and clearly define the diagnostic criteria
[7–11] , there is still a lot of debate concerning
these issues [12] . The most widely accepted defi-
nition currently was proposed by Alberti et al.,
in the Joint Interim Statement. This document
proposes that the presence of three of the fol-
lowing criteria are needed for a diagnosis of MS:
elevated waist circumference (according to pop-
ulation and country-specific definitions) triglyc-
erides 150 mg/dl or greater; high-density lipo-
protein (HDL)-cholesterol lower than 40 mg/dl
in men and 50 mg/dl in women; blood pressure
of 130/85 mmHg or greater and fasting glucose
100 mg/dl or greater. This definition highlights
that there should be no obligatory component
for MS but rather all individual components
should be considered on cardiovascular risk
prediction [13] .
Although the prevalence of MS varies depend-
ing on the criteria used [14] , consistent evidence
show that over the last 20 years, the prevalence
of MS has steadily increased in all populations
worldwide [15] . Although the cause of the syn-
drome remains obscure, it is thought to result
from a complex interaction between lifestyle,

www.expert-reviews.com 10.1586/EEM.11.89 © 2012 Expert Reviews Ltd ISSN 1744-6651 63

 Review Sardinha & Nardi
environmental and biological factors. The central relevance of this
construct lies in its potential use for identifying patients present-
ing an elevated cardiovascular risk and promoting early preventive
lifestyle modifications.
Recent studies on the association between MS and depression
have reported conflicting findings, and little is known about
the role played by anxiety. This study aimed to review the most
relevant findings on the link between MS and psychological
cardiovascular risk factors, focusing on the impact of anxiety.
Methods
PubMed/MEDLINE and ISI/Web of Science electronic searches
of articles were conducted using the following keywords: psycho­
logical, depression, stress, anxiety, behavior, MS, syndrome x,
central adiposity/obesity, visceral adiposity/obesity, waist circum-
ference and insulin resistance/sensitivity. Original and review
papers published since the year 2005 were selected. A further
manual selection was then performed to verify the use of adequate
research methods in the included studies. When more than one
article presented similar information, the most recent one was
retained to provide state-of-the-art information. Other relevant
references cited in the selected papers that were not found by our
primary search were also included.
Results
Psychological factors, diabetes & MS
Depression and anxiety have been independently associated with
an increased risk of both diabetes mellitus and cardiovascular
disease, but the extent to which this risk may be explained by
health behaviors, socioeconomic status and biological mediators is
still unknown [16] . A study conducted with 2997 men and women
supported the hypothesis that depression may increase the risk
for diabetes and suggested that the relationship between negative
mood states and metabolic variables could extend to the whole
population, not only to people diagnosed with either depression
or diabetes [17] .
Type 2 diabetes is also closely related to abdominal obesity and
is generally associated with other cardiometabolic risk factors,
resulting in a high incidence of cardiovascular complications [18] .
Most authors consider the links between cardiovascular disease,
diabetes and psychiatric disorders bidirectional because patients
with anxiety and depression are known to present an elevated
cardiovascular risk and patients with Type 2 diabetes and cardio-
metabolic diseases suffer more frequently from psychiatric prob-
lems [19] . However, results from a prospective population-based
study (n = 37,291) showed that diabetes could not be considered
a predictor of depression or anxiety. Conversely, the presence of
these psychological disorders, and particularly the presence of
comorbidity between depression and anxiety, have emerged as
significant risk factors for onset of Type 2 diabetes independent
of other established risk factors for diabetes, such as lifestyle,
socioeconomic condition and markers of MS [20] .
In addition to poor glycemic control, hypothalamic–pitu-
itary–adrenal (HPA) axis dysfunction, impaired stress responses
and elevated basal levels of glucocorticoids are also hallmark
64
features of experimental models of Type 1 and Type 2 diabetes.
Glucocorticoids regulate many functions of the central nervous
system, such as the activity and direction of intermediary meta­
bolism, the maintenance of a proper cardiovascular tone and the
activity and quality of the immune and inflammatory reaction.
Common behavioral and/or somatic complex disorders, such
as anxiety, depression, insomnia, chronic pain and fatigue syn-
dromes, obesity, the MS, essential hypertension, diabetes Type 2,
atherosclerosis with its cardiovascular sequelae, and osteoporosis,
as well as autoimmune inflammatory and allergic disorders, all
appear to have a glucocorticoid-regulated component [21,22] .
Conversley, Licht and colleagues found that increases in sym-
pathetic and decreases in parasympathetic activity rather than
changes in HPA axis activity are associated with metabolic abnor-
malities, suggesting autonomic nervous system activity is more
strongly associated with MS, than HPA axis activity [23] . Stress
and glucocorticoids contribute to the neurological complications
observed in diabetes patients and many of the hyperglycemia-
mediated changes in the brain are similar to those observed in
depressive and chronically stressed patients; common mech­
anisms may be involved in the development of the neurological
complications related to anxiety, depression and diabetes [22] .
MS & depression
Research efforts to clarify the association between MS and depres-
sion have reported interesting outcomes. A cross-sectional study of
1024 outpatients with stable coronary CAD showed that higher
levels of depression were significantly associated with increased
prevalence of MS and that this could be explained by differences
in socioeconomic status and health behaviors [16] . Data from
Japan have added support for the idea that MS could predict the
development of depression and that the strongest risk factor was
waist circumference (odds ratio [OR]: 2.08; 95% CI 1.23–3.50)
[24] . Another cross-sectional study of 9571 participants in the
Nord-Trøndelag Health Study (HUNT 2) found no relationship
of anxiety and depression with MS [25] .
The direction of the causality of the relationship between MS
and depression; however, remains unclear. A 7-year follow-up of
425 women found that psychological risk factors predicted the
development of MS and that the association between anger and
MS was reciprocal [26] . It is also possible that MS may predis-
pose for depression, leading to a reciprocal association. A 7-year
follow-up study of men and women reported that nondepressed
women and men with MS at baseline were twice as likely to have
depressive symptoms at follow-up (OR: 2.2, 95% CI: 1.1–4.5 for
women; OR: 2.2, 95% CI: 0.8–5.9 for men) as compared with
the nondepressed cohort members without MS at baseline [27] .
In a review study conducted by Rosolová and Podlipný, depres-
sive disorders were nearly twice as frequent in individuals with
MS compared to individuals without MS (relative risk: 1.85;
95% CI: 1.11–3.10) [19] . In three cross-sectional surveys com-
pleted in rural regions of Australia, participants with MS pre-
sented higher scores on depression scales than individuals without
MS. These authors also found this association in MS patients
without diabetes, indicating that the link between psychological
Expert Rev. Endocrinol. Metab. 7(1), (2012)

factors and metabolic alterations is not necessarily mediated by
the presence of diabetes. In this study, large waist circumference
and low HDL-cholesterol showed significant and independent
associations with depression [28] .
In another sample of subjects with MS, depression was approx­
imately four-times more prevalent than in the general popula-
tion. Depressed participants also showed higher heart rate and
sympathetic nervous activity, larger waist circumference, lower
HDL-cholesterol, higher triglycerides and higher BMI [29] .
Among hypertensive subjects with MS, depressive symptoms
along a continuum of severity were independently associated
with multiple unhealthy lifestyles [30] , which adds to the hypoth-
esis of psycho­logical factors contributing to the development of
metabolic disturbances through behavioral aspects.
It has also been hypothesized that gender-specific variables may
mediate this relationship. In a sample of 1598 men and women
at risk for cardiovascular disease, MS was related to an increased
prevalence of depression but not anxiety, and a direct relationship
was observed between the number of diagnostic criteria for MS
and the severity of depression [31] . An Israeli study of 2355 men
and 1525 women found that depression among women, but not
men, was associated with a twofold increased risk of MS and with
an elevated risk of having two of its five components: larger waist
circumference (OR: 2.23) and elevated glucose levels (OR: 2.44).
Among men, depression was associated with larger waist circum-
ference only (OR: 1.77) [32] . In urban Japanese men, depressive
symptoms are considered to be associated with MS and, more
specifically, glucose abnormality (OR: 1.24). No such association
was found for Japanese women [33] .
In a community-based sample of 2917 older persons, the rela-
tionship between depressive symptoms and MS was found in
white (OR: 1.11; 95% CI: 1.01–1.23) but not in black (OR: 0.97;
95% CI: 0.86–1.11) participants [34] . These findings suggest that
the association between depression and metabolic abnormalities
can be mediated by other variables in specific populations and
they highlight the relevance of understanding the roles played by
gender, ethnicity and age when designing interventions.
It is also likely that adaptations to environmental changes play a
role in the dramatic increase in the prevalence of cardiometabolic
risk factors such as obesity, hypertension, Type 2 diabetes, dys­
lipidemias and the MS in industrialized countries. With improve-
ments in economic situation in developing countries, increasing
prevalences of obesity and MS are seen in adults and children [35] .
Another important psychological factor that could increase
psycho­logical distress, anxiety and related MS in underdevelop-
ing countries is stress related to coping with the challenges posed
by urbanization. A study conducted with urban black Africans in
South Africa saw coping disability and anxiety-related symptoms
in relation to MS [36,37] . Results from China showed that the
prevalence of MS was 9.9-times higher in Chinese farmers that
migrated to a big city (23.8%) and 6.3-times higher in Chinese
individuals from an urban environment (15.2%) than in Chinese
farmers (2.4%). The authors attribute the high prevalence of MS
to a change in lifestyle associated with urbanization [38] . Research
carried out in India pointed to a nutrition transition due to rapid
www.expert-reviews.com
The role of anxiety in metabolic syndrome Review
urbanization, combining a decreasing intake of coarse cereals
and vegetables, increasing intake of meat products and salt, with
declining levels of physical activity, that have resulted in escalating
levels of obesity, MS and coronary heart disease [39] .
MS & anxiety
Anxiety triggers activation of the human stress system through
behavioral and physiological changes that improve the ability of
the organism to adjust homeostasis and increase its chances for
survival. These processes appear to adversely affect autonomic
and hormonal regulation, resulting in metabolic abnormalities,
inflammation, insulin resistance and endothelial dysfunction [40] .
The most accepted underlying mechanism relies on the hypoth-
esis that increased activation of the HPA axis could be patho­
physiologically involved in the concomitant occurrence of the
typical MS risk factors and stress.
Patients with anxiety disorders normally present with more
cortisol in the urine than individuals without psychiatric dis-
orders, while there seems to be no difference in the excretion of
catecholamines and serotonin [41] . There is considerable evidence
from clinical, cellular and molecular studies that elevated cortisol,
particularly when combined with secondary inhibition of sex ste-
roids and growth hormone secretions, causes accumulation of fat
in visceral adipose tissues as well as metabolic abnormalities [41] .
Glucocorticoid exposure is also followed by stress-induced over-
eating behavior with increased food intake and leptin-­resistant
obesity, perhaps disrupting the balance between leptin and
neuro­peptide Y [42] . A study using a rodent model of social stress
found that the consumption of a high-fat diet during social stress
enhances the effect of chronic stress on body composition, add-
ing to the body of knowledge about the mechanisms responsible
for the development of obesity, diabetes and, ultimately, MS [43] .
Chronic anxiety and psychosocial stress also produces an array
of adverse health consequences that are highly comorbid, includ-
ing emotional eating, affective disorders and MS. The consump-
tion of high caloric diets is thought to provide comfort in the face
of unrelenting psychosocial stress, in a pattern observed both in
humans and primates [44] . Anxiety disorders are also frequently
accompanied by self-destructive and unhealthy behaviors as well
as medication and treatment non­compliance [40] . Thus, modern
genetic and environmental interactions may explain the explosion
in the prevalences of MS and diabetes in psychologically stressed
humans [15] .
However, available evidence suggests that there is no inde-
pendent association between anxiety and MS. In three cross-
sectional surveys completed in rural regions of Australia during
the 2004–2006 period, MS was associated with depression but
not psychological distress or anxiety [28] . A cohort of 5698 parti­
cipants in Finland presented no clear association of MS with
depression or anxiety [45] . More recently, in a study that sought
to determine the association between the sympathetic firing pat-
tern and anxiety level in patients with MS and elevated blood
pressure, the single-unit sympathetic nerve-firing pattern did
not correlate with any aspect of the metabolic profile; however,
it was significantly associated with anxiety state and trait and the
65
 Review Sardinha & Nardi
affective component of the depression scores. These results lead
the authors to point to an indirect association; as chronic men-
tal stress modulates the pattern of sympathetic activity, this, in
turn, may confer greater cardiovascular risk on individuals with
MS and elevated blood pressure [46] . In a sample of 1217 anxiety
and depressive disorder patients, MS abnormalities are associated
with severity of depression and with tricyclic antidepressant use,
but not with anxiety symptom severity [47] . A review article by
Goldbacher and Matthews proposed that psychological charac-
teristics, especially depression, hostility and anger, may increase
risk for MS, but found no such pattern for anxiety [48] .
The most frequently cited hypothesis explaining the coexistence
of anxiety and MS is that they are indirectly related. Anxiety
and depressive disorders often occur concomitantly, and their
incidence in the general population as well as in chronically ill
individuals may be higher than reported [19] . It is also possible
that metabolic disorders impact HPA axis activity, as proposed
by a study with female MS patients that showed that women
with the abdominal obesity phenotype present alterations of
HPA axis activity independent of the presence of psychological
symptoms [49] .
Some evidence, however, points in the opposite direction. A
large cross-sectional study of 4256 male US veterans surprisingly
found that generalized anxiety disorder, but not major depres-
sive disorder, was positively associated with MS in models that
adjusted for all sociodemographic variables [50] . These authors
discussed the potential roles of anxiety and chronic stress, which
are prominent in generalized anxiety disorder patients, in MS and
suggested that future research focus on these variables. In a com-
munity-based sample of 2917 older persons, anxiety symptoms
were significantly associated with MS in men (OR per standard
deviation [SD]: 1.13; 95% CI: 1.00–1.28), but not in women
(OR per SD: 0.98; 95% CI: 0.89–1.08). These outcomes raise
the question of whether psychosocial risk factors are associated
with MS in an elderly population and whether other variables
may also play a role [34] . In all cases, it seems methodologically
difficult to show an independent role of anxiety as a risk factor for
MS, controlling for the influence of depression and stress (Table 1) .
Endocannabinoid system mediation
In biological terms, the association between MS and increased
cardiovascular risk seems to be mediated by the endocannabi-
noid system (ECS). The mechanism functions through binding
of endocannabinoids at the cannabinoid receptors (CB1), which
regulate appetite and energy homeostasis, emotions such as anxi-
ety and fear, and behaviors such as food and water intake [51] . CB1
receptors are also found in peripheral tissues such as liver, pancreas,
skeletal muscle and adipose tissues, where they play an important
role in lipid and glucose metabolism. Metabolic alterations such as
dyslipidemia, insulin resistance, lipogenesis, excessive weight gain
and increasing intra-abdominal obesity have been associated with
overactivation of the ECS [51] . Recent data suggest that the ECS is
overactivated in the presence of abdominal obesity and/or diabe-
tes, which contributes to further disturbances of energy balance
and metabolism. In addition to regulating the intake of nutrients
66
through central mechanisms located within the hypothalamus and
limbic area, the ECS also intervenes in transport, metabolism and
deposition of nutrients in the digestive tract, liver, adipose tissue,
skeletal muscle and possibly the pancreas. Thus, activation of both
central and peripheral CB1 receptors promotes weight gain and
associated metabolic changes [18] .
Recently, the medical community has shown great interest in
the CB1 receptor antagonists, which were expected to advance
the treatment of obesity and MS. This class of drugs has been
shown to reduce bodyweight, waist circumference, triglycerides,
blood pressure, insulin resistance and C-reactive protein levels
and to increase HDL-cholesterol and adiponectin concentrations
in both nondiabetic and diabetic overweight/obese patients [18] .
However, rimonabant, the first clinically available member of
this class of drugs, has been linked to an increased risk of anxi-
ety, depression and suicidality, and was thus withdrawn from the
market in 2008 [52] .
In behavioral terms, psychological conditions closely related to
chronic stress, such as anxiety and depression, can lead to overeat-
ing, co-elevation of cortisol and insulin levels, and suppression of
certain anabolic hormones. This state of metabolic stress, in turn,
promotes abdominal adiposity. This biochemical environment
appears to be conducive to several cell aging mechanisms and
to influence a variety of diseases through a biochemical cascade
leading to immune cell senescence [41] .
Conclusion
MS is likely to develop in patients in whom genetic predisposition,
chronic stress, negative emotion and unhealthy lifestyle habits
converge. Anxiety and depressive disorders are linked to higher
cardiometabolic risk, higher incidence of acute cardiovascular
events and poorer prognosis for cardiac patients. In addition,
they seem to be comorbid to a range of other chronic internal
diseases. The current literature on the metabolic mediation of
this relationship provides evidence for an association between
psychological characteristics and the development of MS, which
could eventually increase cardiovascular disease risk.
The authors consider the results presented here of consider-
able interest, once the link between psychological variables, such
as depression and stress, and cardiovascular problems have long
been established and the current literature points to an indepen-
dent role of anxiety and negative cardiovascular outcome. This
review shows that even though there is considerable evidence
for the role of anxiety in cardiovascular problems, state-of-the-
art literature does not support that metabolic alterations are a
plausible physiological underlying pathway for this association.
Negative health behaviors and hypothalamic dysregulation and
sympathetic hyperactivation are the most commonly mentioned
plausible underlying pathways (see Figure 1).
Prospective data, although limited, suggest that depression,
stress, hostility and anger, but not anxiety, independently predict
increased risk of developing MS. The coexistence of anxiety in
MS patients seems to be a byproduct of anxiety–depression or
anxiety–stress comorbidity. The HPA axis dysregulation observed
in MS patients may also be explained by alternative factors, such
Expert Rev. Endocrinol. Metab. 7(1), (2012)
 The role of anxiety in metabolic syndrome Review

Table 1. Current evidence on the association of anxiety and depression and metabolic syndrome.
Study (year) Sample Outcome Ref.
Cohen et al. (2010) 1024 stable CAD Higher levels of depression were significantly associated with increased prevalence [16]
outpatients of MS
Holt et al. (2009) 2997 subjects Depression increases risk for diabetes [17]

Engum (2007) 37291 subjects Diabetes could not be considered a predictor of depression or anxiety. The presence [20]
of depression and anxiety represented a significant risk for onset of Type 2 diabetes
Takeuchi et al. (2009) 1183 men MS can predict the development of depression [24]

Hildrum et al. (2009) 9571 subjects No association of anxiety and depression with MS [25]

Raikkonen et al. 425 women Psychological risk factors, particularly anger, predicted the development of MS [26]
(2002)
Dunbar et al. (2008) 1690 subjects Participants with MS with or without diabetes presented higher scores on depression [28]
scales than individuals without MS. No association was found with psychological
distress or anxiety
Petrlova et al. (2004) 116 subjects In MS patients, depression was approximately four-times more prevalent than in the [29]
general population
Bonnet et al. (2009) 840 hypertensive In hypertensive subjects with MS, depressive symptoms were independently [30]
subjects with MS associated with unhealthy lifestyles
Skilton et al. (2007) 1598 subjects MS was related to an increased prevalence of depression but not anxiety [31]

Toker et al. (2008) 2355 men and Depression among women, but not men, was associated with a twofold increased [32]
1525 women risk of MS and elevated glucose levels
Nishnia et al. (2011) 1613 subjects Depression was associated with MS and glucose abnormality in men [33]

Vogelzangs et al. 2917 elderly patients An association between depressive and MS symptoms was found in white but not in [34]
(2007) black participants. Anxiety symptoms were significantly associated with MS in men,
but not in women
Herva et al. (2006) 5698 subjects No clear association of MS with depression or anxiety [45]

van Reedt Dortland 1217 anxious and MS was associated with severity of depression and with tricyclic antidepressant use, [47]
et al. (2010) depressive patients but not with anxiety
Carroll et al. (2009) 4256 men Generalized anxiety disorder, but not major depressive disorder, was associated [50]
with MS
CAD: Coronary artery disease; MS: Metabolic syndrome.

as visceral obesity’s influence on HPA axis activity. Adverse func-
tioning of the ECS can also mediate the stress–fat distribution
relationship.
More prospective studies conducted with diverse samples are
needed to delineate the direction of this relationship and to
assess the roles of the proposed behavioral mechanisms. To test
for causality, further animal experimental investigations might
provide more reliable evidence. Even though the details of the
causal process remain unclear, one can certainly affirm that
patients presenting with psychological distress, such as anxiety,
depressive symptoms and chronic stress, are in danger of meta-
bolic alterations and of a negative cardiovascular prognosis. This
is because the constant activation of the HPA and the sympa-
thetic nervous system promoted by anxiety responses triggers
cardiovascular dysregulations such as elevated heart rate and
blood pressure [53] .
Expert commentary
As science evolves and more complex mechanisms linking
psychological and physiological functioning are disclosed, it
becomes mandatory to address health in a holistic manner. Once
we understand how human psychophysiology functions as an
integrated system, both the physiological and the psychological
variables involved can be manipulated to improve the organism’s
homeostasis.
In other words, if metabolic and psychological disorders both
play a role in cardiovascular outcomes, both issues should be con-
sidered when addressing cardiac health and designing treatment
and prevention interventions. In this sense, mental health profes-
sionals should also take responsibility for addressing detectable
signs of metabolic disorders, such as visceral obesity, and unhealthy
behaviors, such as tabagism, sedentarism and high-fat diet.
Although it is still necessary to determine whether addressing
socioeconomic and behavioral factors in people with depression
or high levels of anger or hostility could reduce the burden of
MS, psychosocial distress is known to be a highly modifiable
risk. Interventions such as psychosocial support, psychotherapy,
regular exercise, stress reduction training and psychotropic medi-
cation have been shown to alter cardiac prognosis in populations
with high cardiac risk [40] .

www.expert-reviews.com 67
 Review Sardinha & Nardi

However, adherence to long-term life-

Stress Autonomic style changes is challenging. Motivational
dysfunction interviewing – a client-centered, directive
counseling approach aimed at promoting
motivation in patients to change certain
Negative behaviors – has been showed to be effective
Metabolic HPA axis
behavioral
syndrome dysfunction in promoting short-term lifestyle changes
Anxiety Depression factors
in cardiac rehabilitation patients [54] , can-
cer survivors [55] , childhood obesity [56]
Endocannabinoid and other health settings, meriting further
system dysfunction investigation. Numerous cognitive and
behavioral evidence-based techniques could
also be potentially useful [57,58] .
Interventions that modify psychological
Increased activation concomitantly to psychological
cardiac risk
symptoms such as biofeedback, relaxation
and other psychophysiologic strategies have
been studied and used in patients with ele-
Figure 1. Psychological factors, metabolic syndrome and cardiac risk.
HPA: Hypothalamic–pituitary–adrenal. ments of the MS, particularly diabetes and
hypertension, being shown to effectively
Screening techniques are available to reliably determine if a patient lower blood glucose and blood pressure [59] .
is at risk for psychosocial stress-related health problems. The pres- Despite the important side effects reported by the inverse ago-
ence of this association indicates that the treatment of these diseases nist for the CB1 medications, the ECS still seems to be the best
as part of secondary prevention in patients with anxiety and depres- candidate for successful pharmacological interventions. A recent
sion must be more rigorous and intensive than in patients without study reuniting the metabolic effects of rimonabant in random-
these psychiatric disorders [19] . Among individuals suffering from ized controlled trials showed that, in all trials, there was a con-
anxiety and/or depression, adhesion to health recommendations is siderable reduction in bodyweight in subjects taking 20 mg of
a cornerstone of cardiovascular disease prevention. rimonabant daily. The lipidemic profile also improved in these
patients, with levels of HDL increasing significantly while levels
Five-year view of triglycerides decreased in all trials. In all cases, prevalence of
As MS seems to be due to the convergence of a variety of factors, the MS decreased significantly. The metabolic changes observed
such as genetic predisposition, chronic stress, negative emotion were partly independent of the weight loss and could be attrib-
and unhealthy lifestyle habits, it is plausible to think that treat- uted to the independent peripheral effect of the drug. It is likely
ment and prevention strategies should address the modifiable that these important findings contribute to further efforts for the
factors. If genetic predisposition and stress triggered by modern development of novel cannabinoid Type 1 receptor blockers with
society cannot be changed, emotional regulation and lifestyle similar metabolic results but decreased prevalence of psychiatric
habits should be focused upon. adverse effects [60] .

Key issues
• Metabolic syndrome (MS) seems to be associated with both psychological factors and increased cardiovascular risk.
• Available evidence suggests that there is no independent association between anxiety and MS.
• The coexistence of anxiety in MS patients seems to be a byproduct of anxiety–depression comorbidity, stress and negative health
behaviors.
• Endocannabinoid receptors, and hypothalamic–pituitary–adrenal axis dysregulation and sympathetic hyperactivation are the most
commonly mentioned plausible biological mechanisms involved in the association of psychological disorders and MS.
• MS is likely to develop in patients in whom genetic predisposition, chronic stress, negative emotion and unhealthy lifestyle habits
converge.
• Mental health professionals should be aware of detectable signs of metabolic disorders and unhealthy behaviors that could lead to an
adverse cardiovascular outcome.
• Cognitive, behavioral and psychophysiologic strategies can be useful to modify negative health behaviors and increase emotional
regulation ability.
• Inverse agonists for the cannabinoid receptor drugs are potential candidates for an efficient pharmacological approach.
• It is possible that regular exercise could be a useful and simple strategy to address psychological disorders and metabolic alterations
simultaneously in both high-risk patients and the general population.

68 Expert Rev. Endocrinol. Metab. 7(1), (2012)

 The role of anxiety in metabolic syndrome Review

Additionally, physical activity is known to positively impact
the prognoses of numerous chronic diseases, particularly cardio­
vascular problems [61] . The prescription of exercise is particu-
larly useful for preventing premature death from all causes,
ischemic heart disease, stroke, hypertension, colon and breast
cancer, Type 2 diabetes, MS, obesity, osteoporosis, sarcopenia,
functional dependence and falls in the elderly, cognitive impair-
ment, anxiety and depression. This benefit is observed in both
sexes and increases with the volume or intensity of exercise [62] .
Regular exercising also seems to play an important role in mental
health maintenance [63] . As we have proposed elsewhere [64] , it
is plausible that regular exercise could be a useful and simple
strategy to address psychological disorders and metabolic altera-
tions simultaneously in both high-risk patients and the general
population.
Financial & competing interests disclosure
A grant was obtained for this review from the Brazilian Council for Scientific
and Technological Development (CNPq) and National Institute for
Translational Medicine (INCT-TM). The authors have no other relevant
affiliations or financial involvement with any organization or entity with
a financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

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71
Artigo 3:
Sardinha A, Nardi AE, Araujo CGS, Ferreira MC, Eifert GH. Brazilian Portuguese
validated version of the Cardiac Anxiety Questionnaire. Arq Bras Cardiol. In Press.

45
 Original Article

Brazilian Portuguese Validated Version of the Cardiac Anxiety

Questionnaire
Aline Sardinha1,2, Antonio Egidio Nardi1,2, Claudio Gil Soares de Araújo5,6, Maria Cristina Ferreira3, Georg H. Eifert4
Laboratório de Pânico e Respiração do Programa de Pós Graduação em Psiquiatria e Saúde Mental do Instituto de Psiquiatria da Universidade
Federal do Rio de Janeiro (UFRJ)1; Instituto Nacional de Ciência e Tecnologia - Translational Medicine (INCT-TM, CNPq)2; Programa de
Pós‑Graduação em Psicologia da Universidade Salgado de Oliveira3; Schmid College of Science and Technology Psychology, Crean School of
Health and Life Sciences - Chapman University4; Programa de Pós-Graduação em Ciências do Exercício e do Esporte da Universidade Gama
Filho5; CLINIMEX - Clinica de Medicina do Exercício6, Rio de Janeiro – Brazil

Abstract
Background: Cardiac Anxiety (CA) is the fear of cardiac sensations, characterized by recurrent anxiety symptoms, in
patients with or without cardiovascular disease. The Cardiac Anxiety Questionnaire (CAQ) is a tool to assess CA, already
adapted but not validated to Portuguese.
Objective: This paper presents the three phases of the validation studies of the Brazilian CAQ.
Methods: To extract the factor structure and assess the reliability of the CAQ (phase 1), 98 patients with coronary
artery disease were recruited. The aim of phase 2 was to explore the convergent and divergent validity. Fifty-six
patients completed the CAQ, along with the Body Sensations Questionnaire (BSQ) and the Social Phobia Inventory
(SPIN). To determine the discriminative validity (phase 3), we compared the CAQ scores of two subgroups formed
with patients from phase 1 (n = 98), according to the diagnoses of panic disorder and agoraphobia, obtained with the
MINI – Mini International Neuropsychiatric Interview.
Results: A 2-factor solution was the most interpretable (46.4% of the variance). Subscales were named “Fear and
Hypervigilance” (n = 9; alpha = 0.88), and “Avoidance”, (n = 5; alpha = 0.82). Significant correlation was found between
factor 1 and the BSQ total score (p < 0.01), but not with factor 2. SPIN factors showed significant correlations with CAQ
subscales (p < 0.01). In phase 3, “Cardiac with panic” patients scored significantly higher in CAQ factor 1 (t = -3.42;
p < 0.01, CI = -1.02 to -0.27), and higher, but not significantly different, in factor 2 (t = -1.98; p = 0.51, CI = -0.87 to 0.00).
Conclusions: These results provide a definite Brazilian validated version of the CAQ, adequate to clinical and research
settings. (Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0)
Keywords: Cardiovascular Diseases; Anxiety; Psychometrics; Psychological Tests; Questionnaires.

Introduction especially in patients with cardiovascular diseases and anxiety

Psychiatric disorders seem to play a role as risk factors
to cardiovascular morbidity and mortality1. They also seem
to have a negative impact on disease stability2, adherence
to treatment 3 and quality of life 4 in cardiac patients.
Despite that, anxiety disorders are often unrecognized
and mistreated in this population, evidencing a gap in the
knowledge in the field5.
Distinguishing between clinically relevant cardiac-related
symptoms and manifestations of anxiety can be challenging,
Mailing Address: Aline Sardinha •
Rua Visconde de Pirajá, 156/404, Ipanema. Postal Code 22410-000,
Rio de Janeiro, RJ - Brazil
E-mail: alinesardinhapsi@gmail.com, contato@alinesardinha.com
Manuscript received April 21, 2013; revised manuscript June 19, 2013;
accepted July 10, 2013.
DOI: xxx/abc.2013xxxx
comorbidity6. The boundaries are usually unclear, negatively
affecting clinical decision-making and treatment7.
Cardiac anxiety (CA) is the fear of cardiac-related stimuli
and sensations, perceived as negative or dangerous8. It is
a syndrome characterized by recurrent aversive sensations
or chest pain, in the absence of physical abnormalities.
Often, individuals with high CA engage in a variety
of hypochondriacal behaviors that raise the risk for
unnecessary diagnostic procedures and cause considerable
expenditure of financial and medical resources9.
CA has been demonstrated in a variety of anxiety-related
conditions, but is also significantly prevalent among cardiac
patients10-12. The cognitive-behavioral model highlights the
role of heart-focused attention and interoceptive conditioning
in the origin of cardiorespiratory manifestations and acute
thoracic pain9. To address these concerns, a psychometric
instrument – the Cardiac Anxiety Questionnaire (CAQ) - was
designed to clinical use in cardiology settings, demonstrating

1

good psychometric properties8. The CAQ has been translated
and tested in different cultures and samples with consistent
results11,13-15. Although the Brazilian translated version of the
instrument has been transculturally adapted, it has not yet
been validated16.
Validations studies of translated instruments allow
comparisons between data from different cultures and
have been demonstrated to be a valuable contribution
to clinical and research practice17. This paper presents a
validation study comprising three distinct phases that aimed
to evaluate the psychometric properties of the Brazilian
adapted version of the CAQ. The objective was to provide
clinicians with an adapted, valid and simple tool to assess
CA in Brazilian cardiac patients.
Methods
Phase 1 - Factor structure and reliability
The initial Brazilian adapted version of the CAQ
consisted of an 18-item 5-point Likert scale as to how
frequently the behavior typically occurs with response
anchors ranging from 0 (never) to 4 (always). Higher
scores indicate greater CA. To extract the factor structure
and assess the reliability of the instrument, this initial
version was administered to 98 patients (61 men) known
to have coronary artery disease (CAD), with ages between
34 and 89 years (mean = 64.2; SD = 10.64). Patients were
recruited in two outpatient cardiac clinics in Rio de Janeiro:
a public outpatient hospital-based service and a private
exercise‑based cardiac rehabilitation program. Thirty eight
percent of the participants had a university degree, whereas
36% had more than eight years of formal education but no
university studies and 14% (n = 14) had up to eight years of
education. All participants signed an informed consent prior
to participation. This study was approved by the institutional
Research Ethics Committee and was funded by research
grants from CNPq, INCT-TM and FAPERJ.
Besides filling in the CAQ, patients were screened for
the presence of psychiatric comorbidities by the same
trained researcher using the MINI – Mini International
Neuropsychiatric Interview, version 5.018. Data from the
MINI was used to assess discriminative validity in the third
phase of this study. The MINI is a short structured interview
designed to explore each of the necessary criteria for the
main diagnoses of DSM-IV, Axis I. Data obtained were
analyzed using the Statistic Package for Social Sciences -
SPSS (version 13).
The first step of the assessment of the factor structure
was to test the sample adequacy, by calculation of the
Kaiser-Meyer-Olkin measure of sampling adequacy, yielding
the significant value of .83. Bartlett's test of sphericity also
resulted in significant sample adequacy (χ = 842,55;
p < 0,001). Factor extraction was assessed by calculating
the exploratory factor analysis using Principal Axis Factor,
with Oblimin rotation. Item-total correlations were also
calculated. To be included in one subscale, item´s factor
loading should be higher than 0.3 in that factor and lower that
0.2 in any other factor19. The number of factors to retain was
Sardinha et al.
Validation of cardiac anxiety questionnaire
Original Article
evaluated using (a) Kaiser's eigenvalue > 1 factor extraction
rule, (b) scree plot analysis20, and (c) the interpretability of
the resulting factor structures21.
Phase 2 - Convergent and divergent validity
Once the Brazilian CAQ basic factor structure and
internal consistency were established, the aim of phase 2
was to explore the convergent and divergent validity of the
scale. For this phase, a different sample of cardiac patients
was recruited in an exercise-based rehabilitation program.
Fifty-six patients with a formal diagnosis of coronary artery
disease were assessed. In this sample, 35 participants were
men and ages ranged from 58 to 94 years (mean = 71.1;
SD = 7.90). All patients read and signed an informed
consent prior to participation. All participants had at least
eight years of education and 67% (n = 37) had university
degree. Patients completed the Brazilian version of the
CAQ, followed by two other questionnaires: the Brazilian
adapted version22 of the Body Sensations Questionnaire
(BSQ)23 and the Brazilian validated version of the Social
Phobia Inventory (SPIN)24.
Briefly, the BSQ is a unifactorial 17-item self-report
questionnaire that assesses the individual's level of fear of
bodily sensations associated with autonomic arousal. Patients
rated the degree to which they experience anxiety as a result
of bodily sensations on a 5-point scale with anchors ranging
from 1 (not frightened/worried by sensation) to 5 (extremely
frightened/worried by sensation)22.
The SPIN is an instrument for the evaluation of fear,
avoidance and physiological symptoms associated with
social anxiety disorder. This is a 17-item scale where each
item can be rated by respondent in a 5-point Likert-type
scale ranging from 0 (nothing) to 4 (extremely), indicating
the level of discomfort experimented in the social situation
presented. The validation process of the Brazilian version
of the SPIN indicated a three-factor structure, composed by
the following subscales: “fear and avoidance of situations of
social evaluation and of figures of authority and physiological
symptoms”, “fear and avoidance of interaction with strangers,
of public speaking, and of being the center of attention” and
“fear and avoidance of social events”24.
We assessed convergent and divergent validity of the CAQ
by computing correlations between CAQ subscales obtained
in factor analysis (phase 1) and the other measurements
subscales. To establish convergent validity, the scores of
the CAQ subscales were correlated to the BSQ total score,
once it presents a unifactorial structure. This instrument was
also used to assess convergent validity in the original scale
validation process and was selected due to the existence
of a Brazilian adapted version and psychometric properties
previously assessed for our population.
Divergent validity was calculated by the correlation
between the scores obtained by the cardiac patients in the
two subscales of the CAQ and the three subscales of the
SPIN. This instrument was selected because social anxiety
should not be conceptually related to the construct of CA.
In the original study, a social anxiety measure was also used
to assess divergent validity.
Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0 2
 Sardinha et al.
Validation of cardiac anxiety questionnaire
Original Article
Phase 3 - Discriminative validity
To determine the discriminative validity of the Brazilian
version of the CAQ we sought to test whether different
groups of cardiac patients presented significant differences
in the CAQ score. We used the same sample of phase
1 (98 coronary artery disease outpatients) and compared
the scores obtained in the CAQ using two different groups
formed according the diagnoses obtained with the MINI –
Mini International Neuropsychiatric Interview version 5.018.
For the purposes of the present study, we screened patients
for present and past prevalence of panic disorder, panic
attacks and agoraphobia, in terms of frequency, and included
those in the so-called “cardiac with panic” patient subgroup.
Patients who met the criteria for mild other psychiatric
disorders but no anxiety disorders were included in the
“cardiac without panic” subgroup. The rationale for this
design was the prediction based in some previous findings
that CA could be associated with a higher prevalence of
current and past panic disorder and agoraphobia diagnosis
or prodromal symptoms10. T-test was used to compare mean
scores obtained in the two subgroups.
Results
In the factor structure study, five factors were identified
with eigenvalues greater than one (eigenvalues: 6.53, 1.81,
1.31, 1.12 and 1.02). Cattell's scree plot analysis indicated
that the factor structure was best described as having either
two, three, or four factors. Thus, solutions with two, three,
and four factors were attempted and subjected to oblique
(Oblimin) rotation. The results clearly indicated that a
2-factor solution was the most interpretable. This solution
accounted for 46.4% of the cumulative variance, with factor
one accounting for 36.39% and factor two, 10.16%.
Theoretical analysis of the items indicated that factor
one combined items that pertained to factors I and III in
the original scale (“Fear” and “Heart-focused attention”)
and were designated in the Brazilian version as “Fear and
Hypervigilance”, comprising nine items. Factor two related
to “Avoidance” and was formed by five items, maintaining
the same structure of the “Avoidance” subscale of the original
instrument. In this solution, items 6, 8, 11 and 18 were deleted
for improving internal consistency. After deleting these items,
the scale was renumbered accordingly. Cronbach's alpha
coefficients for the subscales were, respectively, 0.88 and
0.82. Item-total correlations were assessed for all items
of the CAQ, with all correlations coefficients being higher
than 0.3019. Correlations and rotated factor loadings for the
2-factor solution are presented in Table 1.
In the convergent validity study, a higher direct
significant correlation was found between the “Fear
and Hypervigilance” subscale and the BSQ total score
(p < 0.01), as expected, but a weak non-significant
correlation was achieved with the “Avoidance” subscale.
As normality tests indicated a non-parametric distribution,
Spearman correlations were calculated. Divergent validity
assessment results showed moderate or higher direct
significant correlations between factor 1 and all SPIN
subscales (p < 0.01) and moderate direct and significant
3 Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0
correlations between factor 2 and SPIN subscales
(p < 0.01), except for SPIN factor 2, “fear and avoidance of
interaction with strangers, of public speaking, and of being
the center of attention”. Mean scores, standard deviations
and Spearman correlations between CAQ subscales and the
other measurements are presented in Table 2.
In the discriminative validity phase, the “cardiac with panic”
subgroup consisted of thirty-seven patients (20 men = 54%;
Mean age = 69.5; SD = 11.5 years) that referred panic
disorder or past history of panic attacks, with and without
agoraphobia. From these patients, 6 (16%) met criteria
for current panic disorder, 13 (35%) presented with a past
history of panic attacks and 24 (65%) reported present
agoraphobia, according to the DSM-IV criteria. In this group,
54% (n = 20) patients reported a previous history of acute
myocardial infarction (AMI). In comparison, the “cardiac
without panic” subgroup comprised sixty-one patients
(41 men; 67%), with a mean age of 65.4 years (SD = 9.79).
In this group, 27 patients (43%) reported a history of previous
AMI. Minor differences between these subgroups were not
significant for sex distribution (p = 0.68), history of AMI
(p = 0.74) and mean age (p = 0.18).
As expected, cardiac anxiety was higher in the “cardiac
with panic” subgroup. “Cardiac with panic” patients scored
significantly higher in CAQ factor 1 (t = -3.42; p < 0.01,
CI = -1.02 to -0.27), and higher, but not significantly
different, in factor 2 (t = -1.98; p = 0.51, CI = -0.87 to
0.00). In factor 1, Fear and Hypervigilance, “cardiac with
panic” patients obtained a mean score of 2.98 (SD = 0.91)
whereas those in “cardiac without panic” subgroup
yielded a mean score of 2.34 (SD = 0.91). In factor 2,
Avoidance, patients presented, respectively, mean scores
of 2.81 (SD =1.08) and 2.37 (SD =1.05).
Discussion
The present paper comprised three complementary phases
of psychometric studies that composed the validation process
of the Brazilian version of the CAQ, formerly published in its
translated and transculturally adapted version16. The major
contribution of the current study is to provide a definite Brazilian
validated version of the instrument, composed by 14 items,
to be used in clinical and research settings (see attachment
1), herein called Questionário de Ansiedade Cardíaca (QAC).
Based on the results of these studies, it appears that
the QAC adequately measures cardiac anxiety using two
subscales: fear and hypervigilance of cardiac-related stimuli
and avoidance of activities that could bring on symptoms.
Differently from the original version of the Cardiac Anxiety
Questionnaire 8 , the Brazilian version of CAQ (QAC)
presented a two factor structure in this sample of cardiac
patients in Brazil. Reliability analyses showed that the internal
consistency of both QAC subscale scores was high. Although
these findings provide preliminary evidence that this version
of the instrument can assess CA in Brazilian cardiac patients,
it would be important for future research to confirm the factor
structure and further examine the psychometric properties of
the QAC in more diverse, independent samples to determine
the generalizability of the observed results.
 Sardinha et al.
Validation of cardiac anxiety questionnaire

Original Article

Table 1 - Means (M), standard deviations (SD), corrected item-total correlations (r), and factor loadings of final CAQ items

Items M SD r Factor 1 Factor 2

Factor 1: Fear and Hypervigilance (n = 9)
1. Presto atenção nas batidas do meu coração 2.92 1.37 0.64 0.78* -0.55
3. Meu coração acelerado me acorda à noite 1.78 1.15 0.60 0.83* -0.27
4. Dor ou desconforto no peito me acordam à noite 1.82 1.18 0.59 0.71* -0.06
10. Mesmo que os exames estejam normais, eu continuo me preocupando com o meu coração 3.01 1.59 0.70 0.73* 0.12
13. Preocupa-me que os médicos não acreditem que meus sintomas sejam verdadeiros 2.12 1.53 0.50 0.52* 0.12
14. Quando tenho desconforto no peito ou meu coração está acelerado, preocupa-me que posso
3.17 1.59 0.75 0.79* 0.03
ter um ataque cardíaco
15. Quando tenho desconforto no peito ou meu coração está acelerado, tenho dificuldade de me
2.16 1.21 0.65 0.68* 0.05
concentrar em qualquer outra coisa
16. Quando tenho desconforto no peito ou meu coração está acelerado, fico com medo 2.68 1.50 0.68 0.69* 0.10
17. Quando tenho desconforto no peito ou meu coração está acelerado, gosto de ser examinado
3.45 1.53 0.56 0.63* 0.06
por um médico
Factor 2: Avoidance (n = 5)
2. Evito esforço físico 2.68 1.31 0.62 0.15 0.76*
5. Pego leve o máximo possível 2.87 1.43 0.56 -0.06 0.73*
7. Evito fazer exercícios ou outras atividades físicas 2.16 1.39 0.58 -0.02 0.73*
9. Evito atividades que acelerem o meu coração 2.84 1.47 0.70 0.29 0.67*
12. Evito atividades que me façam suar 2.15 1.44 0.64 0.04 0.74*
Deleted items (n = 4)
6. Verifico minha pulsação 2.50 1.43 - 0.38 0.25
8. Posso sentir meu coração no meu peito 2.81 1.50 - -0.01 0.13
11. Sinto-me seguro estando próximo a hospitais, médicos e outros serviços de saúde 2.96 1.55 - 0.39 0.25
18. Quando tenho desconforto no peito ou meu coração está acelerado, conto para minha família
3.04 1.55 - 0.09 0.30
ou amigos
N = 98. Salient factor loadings (>0.30) are flagged (*)

Table 2 - Means and standard deviations (SD) of convergent and divergent validity measures, and Spearman correlations between QAC,
BSQ and SPIN

Cardiac Anxiety Questionnaire (QAC)

Subscales Mean SD
Factor 1: Fear and Hypervigilance Factor 2: Avoidance
QAC Factor 1: Fear and Hypervigilance 2.17 0.85 - -
QAC Factor 2: Avoidance 1.82 0.81 - -
BSQ (total score) 1.84 0.85 0,58* 0,28*
SPIN Factor 1: Fear and avoidance of situations
of social evaluation and of figures of authority and 0.66 0.71 0,52* 0,24
physiological symptoms
SPIN Factor 2: Fear and avoidance of interaction
0,12
with strangers, of public speaking, and of being the 0.96 0.84 0,45*
center of attention
SPIN Factor 3: Fear and avoidance of social events 0.39 0.78 0,35* 0,20
N = 56. *Correlation is significant at the 0.05 level (2-tailed).

Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0 4

 Sardinha et al.
Validation of cardiac anxiety questionnaire
Original Article
Results from the three phases of the validation process
were presented in terms of the mean scores, considering the
Likert type scale of the instrument1-5 to facilitate comparisons
with other psychometric studies conducted with this
instrument in other populations and languages. For clinical
practice, however, we have observed that some practitioners
find it more convenient to sum up all individual item scores
thereby composing a total score for each subscale. It is
important to notice that all the results presented above would
not be any different if this scoring method had been used.
Although CA was originally conceptualized as a psychological
problem of individuals without physical disease14,25 our present
findings indicate it also may be an issue to be addressed in the
treatment of patients with heart diseases2,3,13,26,27. A greater
focus on these patients is also merited by indications that after
diagnosis is made, they frequently begin to focus intensely on
their heart functioning, are overwhelmed with fear and worry
about their heart2-4,27,28.
It is noteworthy, however, that CA is frequently not
directly associated with behaviors that actually contribute
to reducing cardiovascular risk29,30. Research data indicate
that anxiety symptoms can negatively impact adherence
to exercise programs and medical treatment and,
consequently, negatively affected clinical prognosis3,31,32.
In addition, recent studies have shown that cardiac patients
who experience emotional distress have higher rates of
mortality and morbidity than those who are less anxious
and depressed2,33,34.
The value of using the CAQ for patients with heart disease
has been demonstrated in a previous German study with
90 patients before and after undergoing coronary bypass,
valve replacement or combined surgery27. Not surprisingly,
this study found that all dimensions of CA were elevated
in patients before surgery. However, a different pattern of
findings emerged after surgery. CAQ-Fear was significantly
reduced six weeks after surgery and at six-month follow-up,
whereas CAQ‑Avoidance was stable after surgery but declined
at follow‑up. Approximately 20% of patients continued
to experience clinically elevated levels of CA at six-month
follow‑up. Thus, in contrast to global psychosocial indicators,
which were not very useful in that study, the more specific
assessment of CA may help identify individuals with elevated
levels of CA who might benefit from interventions to help them
adjust to the effects of surgery and lingering cardiac problems.
The level of internal consistency for the subscales found
indicates that simply computing the score of the factors is an
appropriate and useful tool for research and/or clinical screening
activities. Identifying persons who have particularly high levels
of CA and, therefore, may be at an increased risk for elevated
anxious responding to cardiac-related stimuli and sensations
can be a simple screening strategy for the potential need of
psychological interventions, in addition to regular treatment
of cardiological conditions35. Such quick screening could
be particularly useful in busy emergency and/or outpatient
cardiology settings, to avoid unnecessary invasive procedures
and enhance adherence to the treatment prescription5,36.
By using the subscale scores, it also may be possible to identify
which specific aspects of CA are dysfunctionally high and in
need of psychological intervention35.
5 Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0
Data from our discriminative validity study show that
anxious cardiac patients present a significantly higher
average score when compared to cardiac patients without
anxiety. A Norwegian study using QAC in patients
with general genetic risk for arrhythmias referred to a
specialized cardio-genetics outpatient clinics found lower
mean scores of CA than the present investigation (0.6,
0.8 and 1.0, in the three subscales of the original QAC)13.
These relatively low CA scores are consistent with the
hypothesis previously formulated by Sardinha et al that
CA is more strongly associated with presence of psychiatric
comorbidity rather than severity of cardiovascular illness12.
This is also supported by White et al37, who reported a full
mediation of CA in patients with pain non-cardiac chest and
found that those with a DSM-IV Axis I anxiety or mood
disorder were more body vigilant compared to patients
who did not have a disorder. We could expect, however,
that even patients without psychiatric comorbidities, who
already have a cardiac diagnosis, particularly those who
had experienced an acute cardiovascular event, might
present higher scores of CA compared to those with a
general genetic risk, as was demonstrated by Marker et al11.
These authors investigated CA in 658 individuals referred
for electron beam tomographic screening and found that
the group without coronary atherosclerosis had significantly
higher mean CA scores suggesting that people without a
diagnosed cardiac condition pay more attention to and
worry more about their cardiac related symptoms than those
people who have coronary atherosclerosis11.
In this sense, it is likely that a person with high scores
in the QAC could benefit from a more deep psychiatric
investigation to prevent and treat behaviors that could
negatively impair functioning, treatment and prognosis31.
Psychological interventions based on the cognitive behavioral
model of CA used in the QAC should be designed to help
these patients with or without cardiovascular disease to break
the cycle of cardiac-focused anxiety, increased attention
and worry, reassurance-seeking, symptom presentation and
renewed anxiety9,25,31. Following referral, the QAC also may
be useful for identifying the most pertinent treatment targets
and to measure the effectiveness of interventions targeting
specific aspects of cardiac anxiety.
Data from our convergent validity studies show a strong direct
significant correlation between the “Fear and Hypervigilance”
subscale and the BSQ, but a weak and non-significant
correlation with the “Avoidance” subscale. This finding is
actually to be expected because the BSQ assess fear of bodily
events, including cardiorespiratory distress, but it does not
assess avoidance and attention to such stimuli and sensations38.
In this sense, as proposed by the authors of the original scale,
the QAC can be considered a distinct and perhaps more
comprehensive index of CA8. The QAC thus, represent an
important contribution to the assessment of health-focused
anxiety in conditions in which CA is particularly relevant, such
as cardiology settings.
Our data did not provide support to the divergent validity
of the QAC in this population. We can hypothesize that
the shared variation found can be due the fact that patients
who seek much help and reassurance because of their CA

also may fear and worry about public display of autonomic
anxiety manifestations, like tachycardia or trembling ,
as occurs in socially anxious patients. Despite that, the
correlations found between QAC subscale scores and the
results obtained by participants in SPIN subscales indicate
that QAC was unable to adequately distinguish between CA
and social anxiety in this sample. To address that limitation,
we propose the use of other validated psychometric
instruments and, if it is the case, a structured interview such
as the MINI18, to inform differential diagnosis.
Along with that, it would be important to replicate this
validation process using samples from other populations,
such as physically healthy participants and patients with
anxiety disorders, particularly panic disorder, agoraphobia
and generalized anxiety disorder. Our study focused in
validating the QAC in cardiac patients because the main aim
of this effort was to provide a simple tool to help cardiologists
and the general practitioners screen cardiac patients for
cardiac anxiety in order to adequately address psychological
aspects that could impact treatment adherence and prognosis
and inform further psychotherapy referral. In this sense, it
was mandatory to evaluate the psychometric properties
of the instrument in the target population. A greater focus
on patients with CAD also is merited by indications that
after patients have been diagnosed with heart disease, they
frequently begin to focus intensely on their heart functioning,
are overwhelmed with fear and worry about their heart,
become overly dependent on medical and familial resources,
and erroneously avoid activities that may actually strengthen
their myocardium8. It is important, thus, to test whether the
factor structure described herein is confirmed in studies
with different populations before using data obtained with
the proposed version of the QAC with non-cardiac patients.
Fischer et al14 tested and validated a German version of
the Cardiac Anxiety Questionnaire in the general population,
providing normative data for that version14 and confirming
the original three-factor structure subscales: fear (α = 0.86),
attention (α = 0.83), and avoidance (α = 0.81). The same
structure was yield with the Greek version validations
studies, but only after deleting eight items, resulting in a
10-item instrument (fear α = 0.83, heart‑focused anxiety
α = 0.64, and avoidance α = 0.74)15. The Brazilian Version
of the QAC best fit a two-factor solution, merging the fear
and attention subscales, and maintaining the avoidance
subscale, ending up with 14 items. Despite that, the items
that composed the original subscales were confirmed in
the Brazilian version. The present version of the QAC
also reached high Crombach´s Alpha values (fear and
hypervigilance α = 0.88 and avoidance α = 0.82), similar
to the original scale and the other psychometric studies
with this instrument available in the literature.
Another relevant contribution for further studies would
be to generate Brazilian valid normative data and establish
cut‑off points that could better subside clinical decision
Sardinha et al.
Validation of cardiac anxiety questionnaire
Original Article
making, including referral of the patients with high QAC
scores for additional psychosocial assessment and support.
Future research could also add to the psychometric
evaluation of the QAC by studying its test-retest properties,
which is needed to establish the reliability of the scale over
time. Last, the stability of the instrument's factor structure
should be examined in a larger sample using confirmatory
factor analysis.
Conclusion
Our data provide a validated Brazilian version of
the QAC to evaluate CA in patients with cardiovascular
diseases in both clinical and research settings. We hope
this can be a valuable contribution to help cardiologists
and general practitioners adequately identify dysfunctional
manifestations of anxiety that can negatively impact
treatment and inform decision‑making on how to address
this issue in clinical practice. As any other psychometric
instrument, the QAC warrants further studies to verify the
stability of its properties in other contexts.
Acknowledgements
Authors would like to thank Clinimex – Clínica de
Medicina do Exercício and Instituto de Cardiologia Aloysio
de Castro for allowing data collection. This research
received financial support from CNPq, Instituto Nacional
de Ciência e Tecnologia – Translational Medicine (INCT-TM,
CNPq), CAPES and FAPERJ.
Author contributions
Conception and design of the research: Sardinha A, Nardi
AE, Ferreira MC, Eifert GH; Acquisition of data and Writing
of the manuscript: Sardinha A, Araujo CGS; Analysis and
interpretation of the data: Sardinha A, Araujo CGS, Ferreira MC;
Statistical analysis: Sardinha A, Ferreira MC; Obtaining funding:
Nardi AE; Critical revision of the manuscript for intellectual
content: Nardi AE, Araujo CGS, Ferreira MC, Eifert GH.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was
reported.
Sources of Funding
This study was funded by CNPq, CAPES, FAPERJ and
Instituto Nacional de Ciência e Tecnologia.
Study Association
This article is part of PhD dissertation submitted by Aline
Sardinha to the Psychiatry Institute of the Federal University
of Rio de Janeiro.
Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0 6
 Sardinha et al.
Validation of cardiac anxiety questionnaire
Original Article
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 Sardinha et al.
Validation of cardiac anxiety questionnaire

Original Article

Appendix 1:

Questionário de Ansiedade Cardíaca (Versão Validada - Sardinha et al., 2013)

Por favor, avalie cada item marcando a resposta que melhor corresponde ao que acontece com você:

Nunca Raramente Às vezes Frequentemente Sempre

1. Presto atenção nas batidas do meu coração
2. Evito esforço físico
3. Meu coração acelerado me acorda à noite
4. Dor ou desconforto no peito me acordam à noite
5. Pego leve o máximo possível
6. Evito fazer exercícios ou outras atividades físicas
7. Evito atividades que acelerem o meu coração
8. Mesmo que os exames estejam normais, eu continuo me preocupando com
o meu coração
9. Evito atividades que me façam suar
10. Preocupa-me que os médicos não acreditem que meus sintomas sejam
verdadeiros
11. Quando tenho desconforto no peito ou meu coração está acelerado,
preocupa-me que posso ter um ataque cardíaco
12. Quando tenho desconforto no peito ou meu coração está acelerado, tenho
dificuldade de me concentrar em qualquer outra coisa
13. Quando tenho desconforto no peito ou meu coração está acelerado, fico
com medo
14. Quando tenho desconforto no peito ou meu coração está acelerado, gosto
de ser examinado por um médico

Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0 8

Artigo 4:
Sardinha A, Araujo CGS, Silva ACO, Nardi AE. Prevalence of psychiatric disorders
and health-related anxiety in cardiac patients attending a cardiac rehabilitation
program. Rev Psiq Clin. 2011;38(2):61-5.

54
 Artigo original

Prevalência de transtornos psiquiátricos e ansiedade relacionada à saúde em

coronariopatas participantes de um programa de exercício supervisionado
Prevalence of psychiatric disorders and health-related anxiety in cardiac patients attending a cardiac
rehabilitation program
Aline Sardinha1, Claudio Gil Soares de Araújo2, Adriana Cardoso de Oliveira e Silva3, Antonio Egidio Nardi4
1 Psicóloga clínica. Laboratório de Pânico e Respiração do Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (UFRJ). ).
2 Programa de Pós-Graduação em Educação Física da Universidade Gama Filho.
3 Professor adjunto da Universidade Federal Fluminense (UFF).
4 Professor Titular da Faculdade de Medicina, Instituto de Psiquiatria (IPUB)/UFRJ.

Recebido: 26/4/2010 – Aceito: 26/7/2010

Resumo
Contexto: Aspectos psicológicos como estresse e depressão já são reconhecidos como fatores de risco cardiovascular. Mais recentemente, o impacto da ansiedade
passou a ser objeto de estudo. Objetivo: Identificar a prevalência de transtornos psiquiátricos e a presença de ansiedade relacionada à saúde e de ansiedade cardíaca
em coronariopatas participantes de um programa de exercício supervisionado. Métodos: Quarenta e dois homens coronariopatas foram entrevistados com o
Mini International Neuropsychiatric Interview (MINI), versão 5.0, e solicitados a preencher a Escala de Sensibilidade à Ansiedade, o Questionário de Cognições
Agorafóbicas, a Escala de Sensações Corporais e o Questionário de Ansiedade Cardíaca. Resultados: Dentre os participantes, 38% apresentaram um ou mais
diagnósticos psiquiátricos pelo MINI, mas apenas 19% apresentaram múltiplas comorbidades. A presença de transtornos psiquiátricos encontra-se associada a
escores mais altos de ansiedade relacionada à saúde e à ansiedade cardíaca (p < 0,05). Não foi encontrada relação entre os escores de ansiedade e a gravidade da
doença cardiovascular (p > 0,05). Conclusões: Ansiedade relacionada à saúde parece estar mais fortemente associada à presença de comorbidades psiquiátricas do
que à gravidade do quadro cardiovascular. Recomenda-se a triagem regular de pacientes coronariopatas para transtornos psiquiátricos. Estratégias terapêuticas
complementares como exercício físico e psicoterapia podem ser alternativas terapêuticas complementares.

Sardinha A, et al. / Rev Psiq Clín. 2011;38(2):61-5

Palavras-chave: Ansiedade, transtornos psiquiátricos, ansiedade cardíaca, doença arterial coronariana, reabilitação.

Abstract
Background: Psychological factors such as stress and depression have already been established as risk factors for cardiovascular disease. More recently, the
impact of anxiety has been addressed. Objective: To identify psychiatric disorders and assess health- and cardiac-related anxiety in coronary artery disease
patients attending a supervised exercise program. Methods: Forty-two male cardiac patients were interviewed using the Mini International Neuropsychiatric
Interview (MINI) version 5.0 and instructed to complete the Anxiety Sensitivity Index, the Agoraphobic Cognitions Questionnaire, the Body Sensations Scale,
and the Cardiac Anxiety Questionnaire. Results: Thirty-eight percent of the participants presented with one or more psychiatric disorders (PDs) but only 19%
presented with multiple PDs. Psychiatric disorders were associated with higher health- and cardiac-related anxiety scores (p < 0.05). No relationship was found
between these anxiety scores and the severity of cardiovascular disease (p > 0.05). Discussion: Health-related anxiety seems to be more strongly associated with
the presence of psychiatric comorbidities in cardiac patients than with the severity of cardiovascular disease. Screening of all cardiac patients for past and present
psychiatric symptoms should be implemented. Interventional strategies, including exercise and counseling, warrant further research.

Sardinha A, et al. / Rev Psiq Clín. 2011;38(2):61-5

Keywords: Anxiety, psychiatric disorders, cardiac anxiety, coronary artery disease, rehabilitation.

Introdução baixa adesão a programas de reabilitação cardíaca8 e ao tratamento

Condições psiquiátricas têm sido estudadas há muito tempo em
pacientes cardíacos1. A depressão é considerada atualmente não
apenas uma condição associada, mas também um fator de risco in-
dependente para o desenvolvimento da doença arterial coronariana
(DAC)2. Recentemente, estudos têm apontado para a ocorrência de
distúrbios de ansiedade3, notadamente transtorno de pânico (TP)4 e
ansiedade relacionada à saúde5, em pacientes com DAC. Esses estudos
sugerem que ataques de pânico podem gerar déficits de perfusão
miocárdica e um pior prognóstico clínico mesmo em pacientes
clinicamente estáveis6.
A presença de transtornos psiquiátricos como depressão e ansie-
dade contribui não apenas para déficits funcionais em pacientes com
DAC7, como também representa um fator de risco adicional. Além
disso, depressão e ansiedade têm se mostrado fatores preditivos de
farmacológico9. Pacientes com DAC participantes de programas de
exercícios podem ser considerados um subgrupo de pacientes com
DAC com características particulares, e prevalência dessas comor-
bidades psiquiátricas ainda não foi estabelecida para essa população.
O presente estudo teve como objetivo identificar a presença de trans-
tornos psiquiátricos e avaliar ansiedade relacionada à saúde (ARS)
e ansiedade cardíaca (AC) em pacientes com DAC que frequentam
regularmente um programa de exercícios supervisionado.
Métodos
Quarenta e dois pacientes masculinos com DAC participantes de um
programa de exercícios com supervisão médica foram entrevistados
para identificar transtornos psiquiátricos e avaliar ARS e AC em uma
observação transversal. O programa de exercícios é realizado em

Endereço para correspondência: Aline Sardinha. Rua Visconde de Pirajá, 142/1405, Ipanema – 22410-000 – Rio de Janeiro, RJ, Brazil. Telefone: (+55-21) 9417-2708. E-mail: alinesardinhapsi@gmail.com
62 Sardinha A, et al. / Rev Psiq Clín. 2011;38(2):61-5

uma clínica privada, para onde os pacientes são encaminhados por angioplastia coronariana percutânea transluminosa. Além disso, 69%
seus cardiologistas para fins de reabilitação cardíaca. Sessões típicas (n = 29) dos pacientes possuíam diagnóstico de hipertensão arterial,
de exercícios consistiram em 20-30 minutos de exercícios aeróbicos 64% (n = 27) apresentavam dislipidemia e 7% (n = 3) eram fumantes
em esteiras e bicicletas ergométricas, seguidos de 20-30 minutos de atualmente. Outras comorbidades clínicas relatadas foram asma (n = 1),
treinamento de força e exercícios de alongamento. hipotireoidismo (n = 1), histórico de acidente vascular cerebral (n =
Os participantes possuíam um diagnóstico anterior de DAC 2), fibrilação atrial (n = 2), insuficiência mitral (n = 1), endoprótese
documentado por história de infarto miocárdico, procedimentos de de aorta abdominal (n = 2) e endarterectomia de carótida (n = 2). As
revascularização arterial coronariana ou pela presença de significa- informações sobre o uso atual de medicação não estavam disponíveis
tivas lesões obstrutivas comprovadas por angiografia. Os critérios de maneira confiável nos arquivos médicos.
de inclusão foram a concordância em participar, o comparecimento
regular ao programa de exercícios supervisionados (presença em um
mínimo de 75% das sessões) e diagnóstico confirmado de DAC como Prevalência de transtornos psiquiátricos
condição médica primária. Os critérios de exclusão foram a recusa em Dezesseis pacientes (38%) preenchiam critérios para, pelo menos,
participar e a presença de qualquer outra condição médica principal, um transtorno psiquiátrico, quando avaliados pelo MINI (Tabela 1).
como câncer, problemas neurológicos e/ou distúrbios psicóticos. As Oito pacientes (19%) se apresentaram com múltiplos transtornos
informações médicas individuais foram obtidas por meio da revisão psiquiátricos. Nesses pacientes, episódio passado de depressão foi
autorizada dos prontuários. encontrado como sendo o transtorno mais comumente identifica-
Após voluntariarem-se para participar e lerem e assinarem o do (n = 7; 17%), seguido de agorafobia (n = 6; 14%) e fobia social
termo de consentimento informado, os pacientes passavam por uma (n = 6; 14%).
entrevista estruturada destinada a explorar cada um dos critérios Em toda a amostra, apenas três pacientes (7%) estavam atualmen-
do eixo I do DSM-IV para transtornos psiquiátricos (Mini Inter- te recebendo acompanhamento psiquiátrico ambulatorial. Apesar
national Neuropsychiatric Interview – MINI, version 5.0)10. A coleta disso, 26% (n = 11) relataram uso de benzodiazepínicos quando
de dados foi realizada com cada paciente individualmente, antes ou ansiosos, estressados ou com dificuldade para dormir. Os pacientes
imediatamente após a sessão de exercícios, em uma sala separada relataram que os benzodiazepínicos foram prescritos pelos seus
na clínica. Toda a coleta de informações foi realizada pelo mesmo cardiologistas ou clínicos que os acompanhavam no passado, para
pesquisador treinado (A.S.). serem administrados sob demanda. Apenas um paciente afirmou ser
Após a entrevista, foi solicitado aos indivíduos o preenchimento tratado atualmente para ansiedade pelo cardiologista.
dos seguintes instrumentos de autorrelato para investigar ARS e AC: Em relação às manifestações de ansiedade, 24% (n = 10) apre-
o Índice de Sensibilidade à Ansiedade (ASI)11, o Questionário de sentaram pelo menos um transtorno de ansiedade. Embora nenhum
Cognições Agorafóbicas (ACQ)12, a Escala de Sensações Corporais recente ataque de pânico tenha sido encontrado, quatro (10%)
(BSS)12 e o Questionário de Ansiedade Cardíaca (CAQ)13. O ASI é participantes relataram história de ataques de pânico no passado.
um questionário de 36 itens que avalia a extensão do quanto a pessoa O transtorno mais prevalente identificado foi agorafobia sem ataques
acredita que sensações relacionadas à ansiedade podem ser prejudi- de pânico atuais (14%, n = 6). Fobia social estava presente em 14%
ciais à saúde. O ACQ possui 14 itens que se referem a pensamentos (n = 6) dos indivíduos, enquanto transtorno de ansiedade generali-
catastróficos que ocorrem quando a pessoa experimenta ansiedade. zada foi encontrado em 2% (n = 1) dos pacientes e fobias específicas
O BBS possui 17 itens e descreve sensações corporais que podem foram relatadas por 5% (n = 2). Transtorno obsessivo-compulsivo
potencialmente simular ansiedade. Finalmente, o CAQ é um ins- não foi identificado nesta amostra.
trumento de 18 itens destinado a avaliar o quanto o indivíduo julga A prevalência de episódios de depressão em toda a vida foi de
assustadores os sintomas cardíacos apresentados. Todas as medidas 17% (n = 7), enquanto somente 5% (n = 2) preenchiam critérios para
foram instrumentos autoaplicáveis do tipo Likert. Foram utilizadas episódio depressivo maior atual. Um paciente apresentou episódio
versões validadas em português do Brasil14-17. maníaco prévio (2%) e outro (2%) relatou um episódio de hipomania
A presença de transtornos psiquiátricos foi avaliada em termos no passado. Não foi encontrado nenhum paciente com distimia. As
de prevalência atual e em toda a vida e descrita em termos de fre- frequências relativas de cada critério diagnóstico estabelecidas pelo
quência. Para estudar as diferenças nas pontuações de ARS e AC, os MINI podem ser vistas na tabela 1.
pacientes foram divididos em subgrupos de acordo com presença/
ausência de transtornos psiquiátricos e histórico de infarto agudo do
miocárdio (IAM). Uma análise inferencial das principais diferenças
entre as pontuações padronizadas dos questionários foi aplicada por Tabela 1. Prevalência de transtornos psiquiátricos na amostra (MINI*)
testes t e ANOVA, seguidos de análises de post-hoc por Bonferroni se Ao longo
necessário. Foi estabelecido um nível de significância de .05. Todas Presente (n) % da vida %
as análises estatísticas foram aplicadas pelo GraphPad Prism versão (n)
5.0. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa Episódio depressivo 2 4,8 7 16,7
da Universidade Federal do Rio de Janeiro.
Risco de suicídio 1 2,4 1 2,4
Episódio hipomaníaco 0 0 1 2,4
Resultados
Episódio maníaco 0 0 1 2,4
Dados clínicos e demográficos Ataques de pânico 0 0 4 9,5
Os participantes eram 42 homens (erro tolerável = 0,08; intervalo de Agorafobia 6 14,3 - -
confiança de 95%) com idade de 46 a 89 anos (69 ± 9,7; média ± DP). Fobia social 6 14,3 - -
Todos os indivíduos possuíam um mínimo de oito anos de educação Abuso de álcool 0 0 - -
e pertenciam a um status socioeconômico elevado. De acordo com
Tabagismo 3 7,1 - -
suas fichas médicas, 35 (83%) pacientes acompanharam o programa
de exercícios supervisionados três vezes por semana, enquanto 7 Transtorno de ansiedade generalizada 1 2,4 - -
(17%) participaram de quatro a seis vezes por semana. O tempo Distimia 0 0 - -
médio de participação no programa foi de 19,5 meses (DP = 11,1). Sem transtorno psiquiátrico 26 61,9 - -
Cinquenta por cento (n = 21) dos pacientes tiveram pelo menos
Múltiplos transtornos psiquiátricos 8 19,0 - -
um IAM, enquanto 45% (n = 19) passaram por cirurgia de revas-
cularização miocárdica e 60% (n = 25) receberam pelo menos uma *Mini International Neuropsychiatric Interview, versão 5.0.
 Sardinha A, et al. / Rev Psiq Clín. 2011;38(2):61-5 63

Ansiedade relacionada à saúde e ansiedade relacionada à 100

condição cardíaca p = .016

A análise da variância (ANOVA), seguida das comparações post-hoc 80 p = .014

por Bonferroni de pontuações médias padronizadas dos instrumen- p = .016
tos de autorrelato, demonstrou diferenças entre indicadores, com 60 p = .035
pontuações significativamente mais elevadas no CAQ, seguido de

Escores
ASI, o ACQ e o BBS (Figura 1). 40

100 20

80 0
Escores padronizados

BBS ACQ CAQ ASI

60
Sem transtorno psiquiátrico Com transtorno psiquiátrico

40
Figura 3. Ansiedade relacionada à saúde em pacientes com e sem diag-
nósticos psiquiátricos.
20
Como se poderia esperar, a AC era significativamente mais alta
0 nesses pacientes do que a ARS, sugerindo que pacientes com DAC
BBS ACQ CAQ ASI tendem a experimentar mais ansiedade relacionada a seus sintomas
Figura 1. Análise comparativa dos escores médios padronizados das cardíacos em relação a outras sensações corporais.
medidas de ansiedade relacionada à saúde. Apesar da alta morbidade psiquiátrica encontrada no presente
estudo, os pacientes encontravam-se subtratados do ponto de vista
ANOVA: F = 52; p < .0001. Bonferroni: CAQ > ACQ > ASI > BBS; p < .05 psiquiátrico, com apenas três pacientes recebendo tratamento psi-
quiátrico. Mesmo aqueles 26% a que em algum momento foram
Quando os pacientes foram posteriormente divididos em com ou prescritos benzodiazepínicos pelos cardiologistas ou clínicos podem
sem história de IAM, não houve diferenças significativas nas pontua­ não estar recebendo tratamento psiquiátrico adequado. Tais resulta-
ções médias dos questionários que mediam ARS e AC (Figura 2). dos corroboram a importância da realização de cuidadosa triagem
de transtornos psiquiátricos em pacientes com doenças cardiovas-
100
culares. Perturbações psiquiátricas, como ansiedade e depressão,
parecem ser frequentes e subdiagnosticadas em pacientes cardio-
patas ambulatoriais. É provável que a identificação precoce desses
80 sintomas possa reduzir a demanda de uso de benzodiazepínicos por
cardiopatas sem nenhum diagnóstico psiquiátrico preciso, resultando
60 em tratamento mais eficaz, melhor saúde, maior qualidade de vida,
Escores

menor morbidade e redução da mortalidade atribuída à associação

40
20
0 pacientes cardiopatas estudados apresentava múltiplos diagnósticos
BBS ACQ CAQ ASI
Sem história IAM Com história IAM
Figura 2. Ansiedade relacionada à saúde em pacientes com e sem história
de infarto agudo do miocárdio.
Não foram encontradas diferenças significativas.
A média das pontuações dos questionários de ARS e da condição
cardíaca foi significativamente superior quando pacientes com DAC
foram separados de acordo com a presença de transtornos psiquiá-
tricos. Diferenças significativas foram encontradas entre esses dois
subgrupos com todas as medidas, como mostra a figura 3.
Discussão
A alta prevalência de um ou mais transtornos psiquiátricos (38%)
encontrada nesse subgrupo de pacientes com DAC corrobora resul-
tados semelhantes encontrados na literatura1 e destaca a importância
de considerar as consequências da presença de transtornos psiquiá­
tricos entre pacientes que sofrem de problemas cardiovasculares.
entre DAC e distúrbios psiquiátricos2-5.
Apesar de a prevalência descrita neste estudo ser similar àquela
encontrada por outros autores, a relativa baixa prevalência de múlti-
plos diagnósticos psiquiátricos (19%) é um resultado discrepante do
restante da literatura. Bankier et al.1 encontraram que a maioria dos
psiquiátricos. Outros resultados interessantes do presente estudo
incluem a ausência de participantes com ataques de pânico atuais e a
prevalência de episódio depressivo maior e transtorno da ansiedade
generalizada bem menor do que foi encontrado por outros autores
utilizando medidas de autorrelato2-4.
A baixa ocorrência de episódio depressivo maior atual e a au-
sência de ataques de pânico podem ser explicadas de duas maneiras.
É intuitivo pensar que pacientes com ansiedade ou depressão grave
têm menor probabilidade de frequentar regularmente um programa
de reabilitação cardíaca, o que é claramente um viés de seleção que
limita qualquer assunção de causalidade derivada da presente obser-
vação. Por outro lado, existem fortes evidências em relação à melhora
de humor mediada pelo sistema serotoninérgico em pacientes sau-
dáveis que praticam exercício regularmente18. Esse efeito protetor e
terapêutico do exercício sobre sintomas psiquiátricos pode explicar
a baixa prevalência de múltiplos diagnósticos, o que está associado
a uma apresentação menos grave do comprometimento psiquiátrico
e a um melhor prognóstico1.
Outro fator importante é a possibilidade de a relativa baixa pre-
valência de depressão ser devida à ausência de mulheres na amostra,
uma vez que a depressão é mais prevalente em mulheres pós-infarto ou
angioplastia do que em homens com condições físicas semelhantes19.
Em relação aos ataques de pânico, é possível imaginar que uma
pessoa com ataques frequentes poderia desenvolver um compor-
64 Sardinha A, et al. / Rev Psiq Clín. 2011;38(2):61-5
tamento de esquiva ao exercício, o que prejudicaria a adesão a um
programa de reabilitação cardíaca. Especificamente, um programa
de exercícios pode induzir manifestações autonômicas semelhantes
àquelas experimentadas durante os ataques de pânico, determinando
uma esquiva fóbica a essas situações20. Por outro lado, é provável que
a prática regular de exercícios funcione como uma exposição intero-
ceptiva, promovendo dessensibilização gradual dos sintomas autonô-
micos e, assim, reduzindo a frequência e a intensidade dos ataques
de pânico e, até mesmo, produzindo um efeito secundário de reduzir
a esquiva pela redução da ansiedade. De fato, já foi demonstrado
que a prática regular de exercícios físicos reduz a probabilidade de
experimentar um ataque de pânico21. Adicionalmente, pacientes em
tratamento para transtorno de pânico apresentam menores escores
em medidas de qualidade de vida, especialmente aqueles com altos
índices de ansiedade e agorafobia22. O exercício regular poderia ter
um impacto positivo também na qualidade de vida dessas pessoas.
Um dado surpreendente encontrado neste estudo foi a ausência
de diferença significativa em ARS e AC entre pacientes com e sem
história de IAM, uma vez que pacientes pós-AMI têm sido o principal
foco de atenção em estudos que investigam condições psiquiátricas
em pacientes cardiopatas5,9. Esse resultado sugere que todos os
pacientes com DAC, e não apenas aqueles que já passaram por um
evento cardiovascular agudo como o AMI, podem ser beneficiados
pela triagem regular de transtornos psiquiátricos, ARS e AC, de forma
a reduzir os efeitos deletérios potenciais de sintomas psiquiátricos
persistentes, particularmente, da ansiedade.
A avaliação da ARS e da AC pode ser muito importante no sen-
tido de que a persistência de sintomas de ansiedade pode acarretar
prejuízos funcionais5, reduzir a qualidade de vida8, além de afetar
negativamente o prognóstico cardiovascular2-5. Os dados atuais da
literatura apontam para a relevância do impacto cardiovascular nega-
tivo de transtornos psiquiátricos como ataques de pânico6, depressão
e ansiedade2-7. Além disso, ARS e AC crônicas podem induzir um
senso de vulnerabilidade e prejudicar as habilidades de enfrenta-
mento que podem contribuir para o aparecimento de transtornos
psiquiátricos9. Em pacientes com ARS, o reasseguramento por parte
do clínico de que a doença está sob controle não é suficiente. Nesses
casos, a falta de diagnóstico adequado de condições psiquiátricas
como o transtorno de pânico e sintomas de ARS pode acarretar o
uso excessivo dos sistemas de saúde para exames adicionais desne-
cessários, por causa da ansiedade23. É sabido também que problemas
psicológicos secundários a doenças cardíacas ou a um evento cardio-
vascular podem afetar negativamente a motivação do pacientes de
procurar tratamento adequado e de aderir às prescrições médicas5.
Mais especificamente, a adesão a programas de reabilitação cardíaca
pode ser seriamente afetada e esta pode ser considerada uma causa
significativa de abandono desses programas24.
Ainda mais interessante foi o dado de que a ARS e a AC estavam
mais fortemente associadas à presença de transtornos psiquiátricos
do que à gravidade da condição cardiovascular. Tal resultado tem
implicações clínicas significativas no sentido de que a alta prevalência
de transtornos psiquiátricos em cardiopatas, e não a gravidade dos
problemas cardíacos, é efetivamente o fator associado aos altos es-
cores de ARS e AC encontrados nesta população. O resultado de que
qualquer transtorno psiquiátrico, e não apenas de depressão (n = 4)
ou pânico, está associado à maior ansiedade é também clinicamente
relevante, na medida em que isso pode contribuir direta ou indire-
tamente para prejuízos funcionais, menor aderência ao tratamento
e prognóstico mais negativo.
Algumas limitações deste estudo devem ser destacadas. A maior
limitação é a ausência de um grupo de comparação que pudesse
permitir a investigação da possibilidade de vieses de seleção que
comprometessem os resultados desta amostra, além do reduzido
número de participantes. Estudos futuros podem ser conduzidos
comparando subgrupos de pacientes com DAC participantes de
programas de exercício e sedentários, de modo a determinar preci-
samente o tamanho do efeito do exercício regular na prevalência de
transtornos psiquiátricos. Em virtude das limitações já apontadas
dessa observação, uma conclusão definitiva não pode ser obtida.
Entretanto, os dados apresentados se somam ao crescente número
de evidências que corroboram a associação entre prática de exercício
regular e saúde mental.
Outro aspecto a ser destacado é a não representatividade da
amostra em relação à totalidade dos pacientes cardiopatas do Brasil,
especialmente quanto ao nível socioeconômico e educacional dos
participantes. Por outro lado, essa amostra é representativa daqueles
pacientes cardiopatas que efetivamente conseguem ter acesso a pro-
gramas privados de reabilitação cardíaca. Ainda que existam alguns
programas de exercício oferecidos em hospitais públicos, a maior
parte deles é oferecido por instituições particulares e, dessa forma,
acessíveis apenas a indivíduos de nível socioeconômico mais elevado.
Nesse sentido, a presente amostra pode ser considerada adequada
para representar a população-alvo de participantes de programa de
reabilitação cardíaca.
Por último, diferentes diagnósticos cardiovasculares foram agru-
pados neste trabalho como DAC e descritos em termos de frequên­
cia, mas não se encontravam em número suficiente para permitir
análises estatísticas regressivas que poderiam isolar a contribuição
individual de cada condição cardiovascular para cada diagnóstico
psiquiátrico. A maior parte dos estudos publicados anteriormente
apresentava dados de pacientes com condições cardiovasculares
específicas, e o presente trabalho encontrou resultados similares
em termos de prevalência geral de transtornos psiquiátricos entre
participantes com diferentes quadros cardiovasculares e níveis de
gravidade. Acrescenta-se a essa observação o achado de que a gra-
vidade da doença cardiovascular, aqui operacionalmente definida
como histórico de IAM, não parece ter efeito significativo na presença
de ARS e AC. Assim, os resultados deste trabalho apontam para a
importância do rastreamento de sintomas psiquiátricos em todos os
tipos de pacientes cardiopatas.
Conclusão
Os resultados desta pesquisa mostram que transtornos psiquiátricos
são muito prevalentes em pacientes cardiopatas que frequentam um
programa de exercícios supervisionados, ainda que eles se apresentem
menos graves em termos de prejuízos funcionais e a ausência de
múltiplas comorbidades. É possível hipotetizar que o exercício regular
tenha um efeito protetor sobre a probabilidade de desenvolvimento
de transtornos psiquiátricos após um evento cardiovascular, dados
seus efeitos no humor e na ansiedade, especialmente, ARS e AC.
Outra alternativa é que a atividade física possa diretamente contribuir
para menos prevalência de algumas condições psiquiátricas, como
ataques de pânico e episódios depressivos.
Transtornos psiquiátricos em pacientes com DAC e após eventos
cardíacos agudos continuam a ser um tema de grande relevância.
Estudos com intervenções controladas se mostram necessários para
entender mais profundamente a natureza dessa associação, a pato-
fisiologia do seu desenvolvimento, sua significância prognóstica, as
melhores formas de tratamento para alívio dos sintomas e melhora
da sobrevida e uma melhor estimativa dos efeitos da frequência
regular a um programa de exercícios na prevalência de transtornos
psiquiátricos em pacientes com DAC.
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ddad JW, et al. The Cardiac Anxiety Questionnaire: development and
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Artigo 5:
Sardinha A, Araujo CGS, Nardi AE. Psychiatric disorders and cardiac anxiety in
exercising and sedentary coronary artery disease patients: a case-control study. Braz
J Med Biol Res. 2012;45(12):1320-6.

61
Brazilian Journal of Medical and Biological Research (2012) 45: 1320-1326
ISSN 1414-431X

Psychiatric disorders and cardiac anxiety in

exercising and sedentary coronary artery
disease patients: a case-control study
A. Sardinha1, C.G.S. Araújo2 and A.E. Nardi1
1Laboratório de Pânico e Respiração, Instituto de Psiquiatria,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
2Programa de Pós-Graduação em Ciências do Exercício e do Esporte,
Universidade Gama Filho, Rio de Janeiro, RJ, Brasil

Abstract
Regular physical exercise has been shown to favorably influence mood and anxiety; however, there are few studies regarding
psychiatric aspects of physically active patients with coronary artery disease (CAD). The objective of the present study was to
compare the prevalence of psychiatric disorders and cardiac anxiety in sedentary and exercising CAD patients. A total sample
of 119 CAD patients (74 men) were enrolled in a case-control study. The subjects were interviewed to identify psychiatric disor-
ders and responded to the Cardiac Anxiety Questionnaire. In the exercise group (N = 60), there was a lower prevalence (45 vs
81%; P < 0.001) of at least one psychiatric diagnosis, as well as multiple comorbidities, when compared to the sedentary group
(N = 59). Considering the Cardiac Anxiety Questionnaire, sedentary patients presented higher scores compared to exercisers
(mean ± SEM = 55.8 ± 1.9 vs 37.3 ± 1.6; P < 0.001). In a regression model, to be attending a medically supervised exercise
program presented a relevant potential for a 35% reduction in cardiac anxiety. CAD patients regularly attending an exercise
program presented less current psychiatric diagnoses and multiple mental-related comorbidities and lower scores of cardiac
anxiety. These salutary mental effects add to the already known health benefits of exercise for CAD patients.

Key words: Exercise training; Mental health; Depression; Cardiovascular disease; Cardiac rehabilitation

Introduction

Coronary artery disease (CAD) is the leading cause of
death and disability in highly industrialized countries (1).
The literature supports clinically important associations
between psychiatric illness and chronic medical conditions
such as CAD. Depression is currently considered to be a
risk factor for CAD and is also known to adversely affect
self-care and increase the risk of complications and mortality
(2). Although most of the available studies have focused on
the impact of depression in CAD patients, recent evidence
indicates that anxiety and hostility are associated with a
higher number of negative cardiac events (3).
Although there are fewer studies regarding anxiety
disorders compared to depression in CAD patients, robust
epidemiological and clinical evidence shows that they might
play an equally important role. Anxiety has been found to
independently increase the risk of developing CAD in healthy
subjects (4), lead to worsening of existing CAD and also
impact treatment outcomes negatively, as anxious patients
can be less likely to adhere to prescribed medical treatments
(5). The rates of major adverse coronary events, including
recurrent ischemic events and death, in patients with CAD
are significantly increased in patients with depression as
well as in the presence of anxiety (6). In addition, health
care costs are higher and health-related quality of life is
lower in anxious (7) and in depressed patients with CAD
(8). In this respect, anxiety disorders in medically ill patients
should not be ignored and should be considered jointly with
depression when developing strategies for screening and
intervention (2).
Health-related anxiety (HRA) is a specific type of anxiety
that leads to increased worrying about one’s health and
the belief that normal bodily symptoms are threatening,
harmful and medically serious, despite evidence to the
contrary. Hypochondriasis represents an intense form

Correspondence: A. Sardinha, Laboratório de Pânico e Respiração, IPUB/UFRJ, Av. Venceslau Braz, 71, 22290-140 Rio de Janeiro,
RJ, Brasil. E-mail: alinesardinhapsi@gmail.com

Received June 21, 2012. Accepted August 8, 2012. Available online September 28, 2012. Published December 17, 2012.

www.bjournal.com.br Braz J Med Biol Res 45(12) 2012

Psychiatric diagnoses in coronary artery disease patients
of HRA (9). Cardiac anxiety (10), on the other hand, is a
particular presentation of HRA that refers to the fear of
cardiac-related stimuli and sensations based upon their
perceived negative consequences. Because cardiac-related
events are perceived to be aversive and dangerous, this
behavior can promote anxiety that may elicit undesirable
body symptoms (11).
Regular physical exercise has been shown to play an
important role in mental health maintenance (12). The preva-
lence and incidence of depression and anxiety are lower
in those who are regularly active, while being physically
active also seems to reduce symptoms of depression and
anxiety (13). In this respect, exercise training is a healthy
behavior with a minimal risk of adverse events that could be
an effective and practical tool for reducing anxiety among
patients (3). Bearing in mind that exercising could be useful
in the treatment of psychological problems in CAD patients,
the present study aimed to compare the prevalence of
psychiatric comorbidities and the level of cardiac anxiety
in sedentary and exercising CAD patients.
Material and Methods
A case-control study was conducted on a sample of
119 CAD patients recruited from two different institutions,
who will be referred to hereafter as exercise (N = 60) and
sedentary (N = 59) groups. Both groups presented similar
demographic characteristics, differing specifically by the
fact that the exercise group was composed of CAD patients
participating in a supervised exercise program while the
sedentary group consisted of CAD patients from a typical
outpatient clinic with no formal exercise program.
Exercise group
The exercise group consisted of 60 CAD patients at-
tending a medically supervised exercise program. The
CAD patients were referred by their attending cardiologist
and enrolled in the supervised program with no limit in the
duration of participation. Briefly, the exercise session con-
sisted of individualized prescribed 30 min of treadmill and/
or upper and lower limbs cyclergometer aerobic exercises,
followed by 20-30 min of strengthening and stretching
exercises. Data were collected before and after one of the
exercise sessions in a separate area within the clinic in
order to preserve confidentiality. All patients had a formal
diagnosis of CAD, documented by a history of myocardial
infarction or coronary artery revascularization procedures
or by the presence of significant obstructive coronary le-
sions as evidenced by angiography. Inclusion criteria were
agreement to participate, regular compliance (attendance
of over 70% of prescribed sessions) with the supervised
exercise program, and a well-established diagnosis of
current CAD as the primary medical condition. Exclusion
criteria were presence of any other major medical condi-
tion, such as cancer, neurological problems, and known
www.bjournal.com.br
1321
psychotic disorders. Individual clinical data were obtained
by reviewing the medical files.
Sedentary group
The sedentary group consisted of 59 patients consecu-
tively selected from a CAD outpatient clinic in a cardiology
center located in the same part of the city. Patients were
objectively asked if they were actually physically active and
only those with a negative answer to this question were
included in the study. Although these patients’ level of physi-
cal activity or aerobic fitness was not directly or formally
evaluated, they will be considered here as the control group
for this variable. The inclusion and exclusion criteria for
this group were the same as applied to the exercise group,
except for the issue of being regularly exercising.
Procedure
Patients in both groups were interviewed to identify
psychiatric disorders and they filled out a questionnaire
to measure cardiac anxiety. After agreeing to participate
and giving written informed consent, all patients were in-
terviewed by the same trained researcher (A.S.) with the
Mini-International Neuropsychiatric Interview (MINI) (10)
version 5.0. (14), a short structured interview designed to
explore each of the necessary criteria for the main diagnoses
of DSM-IV, Axis I. Psychiatric disorders were assessed in
terms of present and lifetime prevalence (when possible with
the MINI) and in terms of frequency. Information regarding
current tobacco use was also collected.
Later, subjects were requested to fill out the validated
Brazilian version (15) of the Cardiac Anxiety Questionnaire
(CAQ). The CAQ is an 18-item instrument designed to evalu-
ate how threatening the patient considers the experienced
cardiac symptoms (11).
Statistical analysis
To assess differences in the prevalence of psychiatric
disorders (PD) and in cardiac anxiety scores between the
exercise and sedentary groups, inferential analysis was
performed using the software Statistical Packages for
Social Sciences (SPSS version 13). Continuous variables
were compared by the t-test and categorical variables were
compared by the Fisher exact test. Cardiac anxiety (CA)
scores were also analyzed in association with participation
in the exercise program or the sedentary condition using
Pearson’s correlation. The potential participation of exercise
in reducing CA scores was derived using a linear regression
model. Last, the demographic and clinical conditions of
patients who did or did not return the questionnaires were
also compared by the Fisher exact test in order to verify
the existence of possible bias. A level of 0.05 was estab-
lished for statistical significance. The study protocol was
approved by the Universidade Federal do Rio de Janeiro
and Instituto Estadual de Cardiologia Aloysio de Castro
Research Ethics Committees.
Braz J Med Biol Res 45(12) 2012
1322
Results
Demographic and relevant clinical characteristics of
the sample
Exercise group. Patients were 51 men (85%) and 9
women (15%) aged 46 to 89 years (69 ± 9.7; mean ± SD).
Most of the patients attended the sessions three times a
week (87%), while 13% attended 4-6 times a week. Aver-
age time of participation in the program was 19.5 months
(SD = 11.1). Fifty percent (N = 30) had a history of at least
one acute myocardial infarction (AMI) and 60% (N = 36)
were also diagnosed as having arterial hypertension. Only
four (7%) patients currently smoked. Of the 60 patients
interviewed with the MINI, 49 (82%) returned the CAQ. The
non-responders did not differ from the complete sample in
age (P = 0.83), gender (P = 0.63), prevalence of PD (P =
0.73), or in history of previous AMI (P = 1.0).
Sedentary group. This group consisted of a total of 59
patients, 23 (39%) men and 36 (61%) women aged 34 to
87 years (60.7 ± 10.3; mean ± SD). Thirty-one (53%) had
no history of AMI, as opposed to 28 (47%) patients who
had suffered at least one AMI in the past. Fifty-three (90%)
subjects also had hypertension and 6 (10%) currently
smoked. Of the 59 patients interviewed with the MINI, the
large majority (50, 84%) returned the CAQ. The remaining
nine patients did not differ from the complete sample in age
(P = 0.08), gender (P = 1.0), prevalence of PD (P = 1.0), or
history of AMI (P = 1.0).
Prevalence of psychiatric disorders
In the exercise group, 27 patients (45%) met the criteria
for at least one psychiatric diagnosis, as explored by the
MINI, and 13 patients (21%) presented multiple PD. On the
other hand, 48 patients (81%) in the sedentary group had
one or multiple PD (P = 0.000). There was also a compa-
rable higher number of patients from the sedentary group
with multiple PD (N = 32; 54%; P = 0.001).
In the exercise sample, only 3 patients (5%) were cur-
rently seeing a psychiatrist in outpatient clinical treatment,
while among the sedentary patients, 2 (3%) reported being
seen by a psychiatrist and were currently medicated with
antidepressants and mood stabilizers, a difference that was
not statistically significant (P = 0.66). Nevertheless, in both
settings, patients reported using benzodiazepines on an ir-
regular basis, whenever anxious, stressed of having sleep
difficulties, normally prescribed by the cardiologist. Based
on patients’ self report, none of the patients in the two set-
tings were being regularly submitted to cognitive behavioral
therapy (CBT) or other forms of psychotherapy. Also, none
of the outpatient clinics where data were collected offered
any kind of psychological support.
Among the exercise patients, past depression was found
to be the most commonly occurring disorder and was associ-
ated in most cases with generalized anxiety disorder (GAD)
and agoraphobia. All GAD cases (N = 3, 5%) were subjects
Braz J Med Biol Res 45(12) 2012
A. Sardinha et al.
with multiple PD. Lifetime prevalence of depressive episode
was 15% (N = 9), while only 7% (N = 4) met the criteria for
a current major depressive episode. One patient had previ-
ously experienced a manic episode and three (5%) reported
a hypomanic episode in the past. No cases of dysthymia
were found. Two patients (4%) met the criteria for alcohol
abuse. No other drug abuse was reported.
Although past depression was also relatively prevalent
among sedentary patients (N = 13, 22%), no significant
difference was found between the exercise and sedentary
groups (P = 0.344). Current depression was the more
expressive PD found in these patients (N = 18, 30%),
representing an expressive difference from the four cases
(7%) identified in the exercise group (P = 0.001). A past
maniac episode was reported by 1 patient and only 3 re-
ported a history of hypomaniac episodes. In this group, 6
(10%) patients were diagnosed with dysthymia according
to the MINI. No alcohol or other drug abuse was reported
by this sample.
Concerning anxiety manifestations, 42% (N = 25) of
the subjects in the exercise group reported at least one
current anxiety disorder, while among sedentary patients,
33 (56%) presented one or multiple anxiety disorders. No
current panic attacks were reported by patients in the ex-
ercise group, as opposed to 12% in the sedentary group.
Considering a lifetime timeframe, 6 (10%) participants in
the exercise group and 10 (17%) in the sedentary group
reported a history of panic attacks (P = 0.40).
The most prevalent disorder identified in the exercise
group was agoraphobia without panic attacks (18%, N =
11), which was also highly prevalent in the sedentary group
(N = 15, 25%; P = 0.260). Social phobia was present in
12% (N = 7) of the exercisers and in 17% (N = 10) of the
sedentary patients (P = 0.84). Generalized anxiety disorder
was about equally present in exercising patients (N = 3,
5%) and in the sedentary group (N = 7, 12%; P = 0.31).
Obsessive-compulsive disorder was not diagnosed in any
of the patients from the two groups. The frequencies and
comparisons of each PD in both groups as established by
the MINI are shown in Table 1.
Ninety-nine of the 119 patients (83%) returned the
CAQ (49 exercisers and 50 sedentary subjects). The mean
scores significantly differed between the two groups (37.3
vs 55.8, respectively; P < 0.001; 95%CI = 13.47 to 23.55),
with exercisers presenting lower CA scores than sedentary
subjects (see Figure 1).
The severity of cardiovascular disease, defined by a
history of AMI, on the other hand, did not influence the CA
scores (P = 0.936, 95%CI = -6.55 to 6.03); however, when
comparing the mean scores of patients with and without a
psychiatric diagnosis, regardless of whether the patients
were physically active or not, there were significant differ-
ences indicating that those who presented at least one
psychiatric condition had higher CA scores (P = 0.018,
95%CI = -2.14 to -1.37).
www.bjournal.com.br
Psychiatric diagnoses in coronary artery disease patients 1323

Table 1. Prevalence of psychiatric disorders in exercising (N =

CA score, but the association was weak and not relevant
60) and sedentary (N = 59) coronary artery disease patients.
(r = 0.193; P = 0.057).
In a regression model, the regular participation in an
Exercise Sedentary exercise program presented a potential determination (R2)
group (%) group (%)
of 35.6%, statistically significant (F = 53.177; ß = -0597; P
Variable Current Lifetime Current Lifetime < 0.001), in the reduction of CA. By adding the presence
or absence of a psychiatric diagnosis to this model, the
Depressive episode 7 15 30 22
increase of potential impact was not significant (P = 0.974).
Suicide risk 2 0 2 0
None of the other variables inserted significantly increased
Bipolar disorder 0 7 0 5
the determination potential.
Panic disorder 0 10 12 17
Agoraphobia 18 0 25 0
Discussion
Social phobia 12 0 17 0
Alcohol abuse 4 0 0 0 The results reported here reveal that CAD patients
Smoking 12 0 10 0 who were regularly attending a medically supervised ex-
Binge eating episodes 8 0 10 0 ercise program presented less current PD, fewer anxiety
Generalized anxiety 5 0 12 0 disorders and depression, lower indices of multiple PDs
disorder
and lower CA scores. The cross-sectional methods used
Dysthymia 0 0 10 0
do not permit to infer causality between a regular exercise
No psychiatric disorder 55 19
pattern and the presence of PD and CA in these patients.
Another limitation of our methods is that the use of the
DSM categorical criteria in a structured interview (MINI)
to identify psychiatric comorbidities does not inform about
the severity of the disorders, but only about its presence
or absence. Nevertheless, our data provide clear evidence
that CAD patients currently attending a regular exercise
program seem to be psychologically healthier than physi-
cally inactive patients.
Additionally, the 45% prevalence of PD in exercising
patients confirms the current difficulties among health care
providers to recognize and treat psychological disorders in
CAD patients. This may add to the hypothesis of Roy-Byrne
et al. (2) that health care professionals tend to underestimate
anxiety in chronically ill patients, as they consider it to be
Figure 1. Scores of the Cardiac Anxiety Questionnaire, which an unimportant response to illness.
was returned by 99 of the 119 patients studied (83%; 49 exercisers The prevalence of a major depressive episode was
and 50 sedentary subjects). The mean scores of exercisers were the most marked difference between the two groups, with
significantly lower than those of sedentary subjects (P < 0.001,
current depression being the more expressive PD found
95%CI = 13.47 to 23.55, t-test).
among sedentary patients (30%) compared to only 7% in
the exercise group. Depression is associated with decreased
The correlation between duration of participation in the adherence to medications, a triple risk of noncompliance
exercising group and CA scores was also analyzed. Average with medical treatment regimens (1) and reduced chances
time of participation in the exercise program was found to of successful modifications of other cardiac risk factors
be 19.5 months (SD = 23.57 months), with a wide range of and adherence to cardiac rehabilitation (16). It is possible
variance between participants (min = 1; max = 168 months). that exercise intervention played an independent role in
Given this non-parametric distribution, Spearman’s corre- reducing depression in the exercise group. A review pub-
lation was used to establish the association. A weak and lished by Dunn et al. (17) showed that numerous studies
nonsignificant correlation of r = 0.219 (P = 0.147) was found report a positive effect of exercise of different intensities on
between length of participation and higher CA scores. depressive symptoms. More recently, two review studies
There was a significant association between CA scores provided substantial data, especially from cardiac rehabili-
and presence of psychiatric diagnosis (r = 0.239; P = 0.018). tation and exercise programs, demonstrating the role of
On the other hand, there was a strong inverse correlation physical activity and cardiorespiratory fitness in improving
coefficient between exercise and CA score (r = -0.597; P psychological risk factors such as depression, anxiety,
= 0.000). The increase in the number of psychiatric comor- hostility, total psychological stress, as well as stress-related
bidities seemed to be directly associated with an increased mortality (18,19).

www.bjournal.com.br Braz J Med Biol Res 45(12) 2012

1324
Although depression may also be a barrier to par-
ticipation in cardiac rehabilitation and exercise programs,
cardiologists can help depressed patients overcome this
barrier by providing encouragement (1) or referring them to
adequate psychological interventions. CBT has been shown
to directly reduce depression in CAD patients (20), helping
to overcome social isolation and counseling patients on how
to adapt to a healthy lifestyle (21) and could probably be a
useful tool to motivate and guide patients toward lifestyle
modification and adherence to rehabilitation treatment. CBT
incorporates techniques such as self-monitoring, problem
solving, and mutual goal setting that reinforce the benefits of
exercise as well as other essential self-care strategies that
improve clinical outcomes in cardiac patients (10). Depres-
sion guidelines for the primary care population have docu-
mented that treatments with appropriate pharmacological
agents and behavioral interventions are similarly effective
and their combination has the benefit of lowering relapse
rates (1). Janeway (21) also proposed that, since CBT is also
a well-documented evidence-based treatment for anxiety
disorders, it should be instituted at the beginning of CAD
treatment to ensure that patients understand their condition
and improve adherence to treatment. Unfortunately, none
of the outpatient clinics where data were collected offered
any kind of psychological support.
No significant differences were found in psychiatric
medication use between groups. However, a limitation of
our method was that information about medication and dos-
age was collected on a self-report basis, which negatively
affects the reliability of the data and prevents more in-depth
conclusions about the potential effects of psychiatric drugs
on the results obtained.
The high association found between depression and
GAD was consistent with literature reports. Although GAD
can precede depression and eventually develop into de-
pression, preliminary longitudinal findings suggest that the
presence of GAD in patients with major depression does
not have prognostic significance in terms of psychiatric
impairment (22). Conversely, cardiovascular prognosis
in GAD and depressed patients seems to be negatively
impacted (6), indicating the need for specific assessment
for the presence of GAD and adequate treatment.
Herring et al. (5) found that exercise programs using ses-
sion durations of at least 30 min, and an anxiety report time
frame greater than the past week yield large improvements
in anxiety symptoms among sedentary patients who have a
chronic illness. Sardinha et al. (23) recently reported a panic
disorder case with a favorable response to the inclusion of
a 12-week exercise program in the context of CBT. In our
study, average time of participation in the exercise program
was somewhat longer (mean of 19.5 months), indicating
that the impact of exercise on anxiety reduction might last
when regular exercise is maintained. Perhaps most im-
portantly, anxiety reduction was favorably associated with
a nonspecific anxiety-focused exercise intervention since
Braz J Med Biol Res 45(12) 2012
A. Sardinha et al.
the exercise program studied was designed as adjuvant
treatment only for CAD.
Another aspect to be highlighted is the absence of cur-
rent panic attacks in the exercise group compared to a 12%
rate among sedentary CAD patients. Although panic disor-
der patients may possibly avoid participating in a regular
exercise program, it seems plausible to hypothesize that
exercise might have played a role in reducing panic when
considering available evidence from the literature (24).
Strohle et al. (25,26) demonstrate in various studies that
exercise promotes an acute anti-panic effect in healthy as
well as in panic disorder patients (27). Potential underlying
mechanisms of this association seem to be the serotonin
system (5,25) and, as reported more recently, the brain-
derived neurotrophic factor (28).
Agoraphobia, although responding to different pharma-
cological drugs (29), seems not to be significantly influenced
by exercise training. Considering the existing evidence
that exercise tends to reduce anxiety sensitivity (30), this
result may seem puzzling. The rationale of the positive
impact of physical activity on anxiety sensitivity relies on
the assumption that exercising could be seen as an indi-
rect desensitization process, since autonomic alterations
triggered by exercising are similar to anxiety symptoms,
but elicited in a safe context (23,30). As the agoraphobia
criterion present in the MINI does not focus on the anxiety
sensitivity cognitions of the patients, “the fear or the fear”,
but on the avoidance behaviors, we can hypothesize that
the reduction of anxiety sensitivity promoted by exercise
could not be assessed with our methods. This could be
reinforced by the finding that cardiac-anxiety cognitions
were significantly reduced among exercisers, showing that
when we consider the more specific aspects of the health-
related anxiety present in agoraphobic patients, exercise
seems to play a positive role.
Cardiac anxiety reduction derived from regular exercise
attendance could as well be used to prevent the develop-
ment of agoraphobic and “panic-like” cognitions and conse-
quent avoidance behaviors in CAD patients at the beginning
of treatment. It could be expected that patients after being
diagnosed with CAD become worried about their health, and
particularly their heart. Health-related anxiety seemed to be
more strongly associated with the presence of psychiatric
comorbidity than the severity of the cardiovascular condi-
tion, confirming data previously reported by Sardinha et al.
(31) regarding CAD patients. As regular exercise was the
factor most strongly associated with reduced CA in these
patients, this emphasizes the relevance of considering
the prescription of regular exercise for CAD patients, not
only for the cardiovascular benefits, but also as a form of
secondary prevention of CA and its deleterious effects on
adherence to medical treatment, self-care and subsequent
prognosis for these patients.
In this respect, CBT and exercise programs could be
used jointly to prevent the negative impact of CAD on the
www.bjournal.com.br
Psychiatric diagnoses in coronary artery disease patients
patient’s mental health, improving treatment adherence,
functioning and clinical prognosis (24). Interventions de-
signed to address both physical and psychological symp-
toms may provide the best method for optimizing functioning
and enhancing quality of life in CAD patients (10). Aerobic
exercise may reduce depressive and anxiety symptoms
in addition to improving cardiovascular fitness. Exercise
training can be especially useful for patients who prefer
non-pharmacologic treatments for their psychological prob-
lems (5). The present study provides clinicians with further
evidence to recommend exercise training to their patients
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www.bjournal.com.br
Artigo 6:

Sardinha A, Gomes RM, Araujo CGS, Freire RCR, Mochcovitch MD, Deslandes AC,
Nardi AE. The mediation role of psychological and cardiorespiratory variables in the
therapeutic effect of an aerobic exercise protocol for Panic Disorder. Em finalização.

69
 The mediation role of psychological and cardiorespiratory variables in the

therapeutic effect of an aerobic exercise protocol for Panic Disorder

Aline Sardinha
Raphael Marques Gomes
Claudio Gil Soares de Araújo
Rafael Cristophe da Rocha Freire
Marina Mochcovitch
Andrea Camaz Deslandes
Antonio Egidio Nardi

Em finalização

1
Abstract

Literature provides evidence of a positive effect of combining aerobic exercise to regular

therapy in the treatment of Panic Disorder (PD). This study sought to further understand

the behavior and interactions between the psychological constructs implicated in the

psychopathology of panic and cardiorespiratory variables modified by aerobic training.

Fifteen patients with PD completed a 12-week treatment period in pharmacological or

pharmacological + exercise conditions. Data collection used Panic and Agoraphobia

Scale, Anxiety Sensitivity Index, Agoraphobic Cognitions Questionnaire, Body

Sensations Questionnaire, Cardiac Anxiety Questionnaire, Mobility Inventory for

Agoraphobia and the State Trait Anxiety Inventory. Physiological variables were

acquired before and after 12 weeks by a maximum cardiopulmonary exercise test and in

each exercise session. Patients who exercised along with pharmacotherapy improved

significantly regarding most subscales of the instruments. Exercise seems to present a

selective, rather than a general ansiolytic impact. An early expressive effect was found in

aspects concerning fear of physiological arousal, interoceptive conditioning and in the

frequency and intensity of PA. Smaller latter effects were observed in health and

physical concerns and agoraphobic cognitions, with no consistent impact in

agoraphobia. Aerobic exercise training was well tolerated and able to induce significant

improvements in several indicators of maximal performance and fitness. Interactions

between cardiorespiratory and psychological variables are discussed. Exercise might

play a double role in the treatment of PD: psychological symptoms and cardiovascular

risk reduction.

Introduction

Panic disorder (PD) patients present anxiety regarding the occurrence of benign

2
body symptoms and autonomic arousal, developing hipervigilance to and avoidant of

situations that could elicit the feared somatic manifestations. Cognitive Behavioral

Therapy (CBT) approach to panic highlights the role of misinterpretation of physical

symptoms as threatening in increasing anxiety (1). These cognitive biases contribute to

the subsequent establishment of an interoceptive conditioning that worsens somatic

manifestations and maintains the panic cycle (2-4). Interoceptive exposure techniques -

the voluntary exposure of the patient to autonomic manifestations - have a therapeutic

effect in the treatment of PD by promoting habituation to physiological cues and

consequent anxiety reduction, contributing therefore to break the hipervigilance-anxiety-

panic-avoidance cycle (5).

Anxiety sensitivity (AS), or the belief that anxiety-related sensations can have

negative consequences, plays an important role in the etiology and maintenance of PD

(6). The single presence of AS, regardless meeting full criteria for PD, often predicts

panic symptoms in response to biological challenges that provoke feared bodily

sensations, consisting in a risk factor for panic attacks (PA) and perhaps PD (7). It has

been hypothesized, additionally, that high AS might be the missing piece to explain

agoraphobic avoidance in the absence of PA (8).

As aerobic exercise involves exposure to physiological stimuli similar to those

experienced during anxiety reactions, PD patients often experience anxiety and avoid

exercising. In a study designed to evaluate the acceptance of an exercise program in

patients with anxiety disorders, only 45% of participants presented the recommended

levels of physical activity for health at baseline (9). Consistent with that, in a

cardiovascular fitness assessment, PD patients exhibited lower maximum oxygen

uptake (VO2 max) and decreased exercise tolerance than nonclinical subjects (10).

These findings are consistent in literature and confirmed by direct interviews considering

habits of physical activity (11).

3
 It is also plausible that the observed reduced aerobic fitness might contribute to

the pathophysiology of PD and AS maintenance. This could be explained by the fact that

sedentary individuals tend to present increased sympathetic response to physical effort

during daily activities (12), which can trigger more anxiety responses and consequent

situational avoidance. Smits and Zvolensky found that current physical inactivity was

significantly associated with greater levels of AS and severity of PD in a clinical sample

(13). Ehlers et al reported that patients that seek medical help for benign palpitations

could be distinguished from those with arrhythmia, among other variables, by presenting

lower levels of physical activity and higher levels of AS (14). Also, a case-control study

performed with sedentary and exercising cardiac patients found that individuals who

participated in a supervised exercise program presented significantly less PD and

cardiac anxiety (15).

Therefore, in the long run, exercise avoidance and low levels of physical activity

in leisure time turn out to promote a sedentary lifestyle as an indirect effect of PD (16).

Paradoxically, elevated health-related anxiety, AS and PD seem to contribute to

unhealthy life habits. In a previous review, Sardinha et al. found evidence for the

hypothesis of an indirect relationship between anxiety and metabolic syndrome as a

byproduct of an unhealthy lifestyle (17). Combined with the already established weight

gain side-effect of psychotropic medication used to treat anxiety disorders, particularly

antidepressants, sedentary behavior also might play a role in raising the prevalence of

obesity (18) in anxious patients. Furthermore, a higher prevalence of sedentary habits,

obesity and metabolic syndrome associated with anxiety disorders might be possible

underlying mechanisms that contribute to increasing cardiovascular risk in this

population (16, 17, 19).

Moreover, a recent study found that both strength and endurance training

effectively reduced C-proteins serum levels by 20% in anxious patients (20). In this

4
sense, psychological interventions designed to address AS, health-related anxiety and

exercise avoidance, as well as the insertion of exercise protocols in addition to regular

treatment of anxiety disorders, could have a potential positive effect of patients´

cardiovascular health prognosis (19) and quality of life (21) after symptom remission.

Abounding evidence demonstrate the role of exercise in lowering the prevalence

of anxiety, raising the question whether exercise may be used in the prevention of

mental disorders (22), and particularly in the treatment of PD (23). An acute immediate

anti panic effect of aerobic exercise had been demonstrated in laboratory panic induction

protocols using cholecystokinin tetrapeptide (CCK-4) (24) and CO(2) inhalation (25).

This effect has been demonstrated in healthy individuals (26) as well as in PD patients

(27), with some evidence for a dose-response relationship favoring moderate to intense

exercise in the reduction of panic symptoms. Strohle et al advocate that this effect is

probably due to the observed brain derived neurotrophic factor (BDNF) serum

concentration increase yield in PD patients, approaching healthy controls reported

levels, after a 30-min exercise session (28). Another study by the same group also found

that the anxiolytic activity of exercise was correlated with the increase in plasma atrial

natriuretic peptide (ANP) concentrations (29).

Comparative studies have shown a therapeutic effect of aerobic exercise in the

treatment of PD (23). Broocks et al compared a 10-week running program with

clomipramine and placebo pills and found that regular aerobic exercise alone, versus

placebo, was associated with significant clinical improvement, but less effective than

clomipramine (30). It was hypothesized that this effect was mediated by exercise impact

in the serotoninergic system, based on the findings that regular physical activity is

associated with decreasing somatization, probably through adaptive mechanisms of

serotonergic circuits implicated in anxiety and nociception regulation (31). This was

supported by further studies that showed reduced 5-HT1A responsivity in patients with

5
PD (32) and a downregulation of central 5-HT2C receptors in healthy volunteers after

10-weeks of jogging three times a week in healthy volunteers (33).

Despite the positive effects of exercise alone, a randomized controlled trial that

compared the addition of a 10-week aerobic exercise protocol and relaxation training to

paroxetine found no differences between interventions (34). Nocturnal cortisol excretion

analysis of those patients found no relationship between hypothalamo-pituitary-

adrenomedullary (HPA) activity and treatment response nor with exercise (35).

Another study that added a home-based walking program to CBT in patients with

anxiety disorders found significant decrease in stress, depression and anxiety levels in

comparison to the group that received regular CBT (36). When compared versus CBT,

however, a 12-week exercise protocol showed poorer results in the Mobility Inventory

(MI), the Agoraphobic Cognitions Questionnaire (ACQ) and Body Sensations

Questionnaire (BSQ) than the established treatment (37).

Interestingly, while AS predicts exercise avoidance and low adherence, aerobic

exercise-based interventions seem to reduce it. Six 20-minutes exercise sessions were

sufficient to demonstrate a decrease in AS levels (6). Considering exercise intensity,

results by Broman-Fulks et al. indicated that both high- and low-intensity exercise

reduced AS. However, high-intensity exercise accounted for more expressive outcomes

and was the only to reduce fear of anxiety-related bodily sensations (38). Another recent

study found that a single session of psychoeducation combined with interoceptive

exposure was effective to reduce AS and outcomes were maintained in a six-month

follow-up (39). However, while in PD patients exercise present poorer results than CBT,

when it comes to reducing AS levels in high-AS score individuals, no additional effect of

a cognitive restructuring intervention was observed in a 2-week trial, being both

conditions more effective than waiting list control.

It seems that changes in AS mediate the beneficial effects of exercise on anxious

6
and depressed mood (40). It is plausible that, as aerobic exercise involves exposure to

physiological cues similar to those experienced during anxiety reactions, the

participation in exercise programs might have a similar role in the treatment of AS and

panic to the already established interoceptive exposure techniques. Thus, if exercise is

administered in gradual increase intensity, it may have a habituation effect on the

interoceptive conditioning underlying AS and panic (19). It is also possible that other

constructs that participate in the psychopathology of PD, such as cardiac anxiety,

agorafobic cognitions, fear of body symptoms, hipervigilance and avoidance might be

differentially influenced by exercise interventions.

Although the evidence for positive effects of exercise on anxiety is growing, its

clinical use as an adjunct tool to established treatment approaches like CBT or

pharmacotherapy, is still insipient (22). Specific investigations on its the clinical effects,

interaction with standard treatment approaches and details on the optimal type, intensity,

frequency and duration that might further support the clinical administration in patients

are still lacking.

Also, even though addition of exercise interventions to regular therapy seem

promising, adherence is often mentioned as a challenge in this population, with dropout

rates yielding 30%, approximately (30). A pilot study of acceptability and adherence to

CBT + exercise showed a significant drop in exercise session participation along time

(9), which is consistent with the high exercise avoidance in PD patients mentioned

above. To the moment, there is a gap in the knowledge on how to best deal with anxiety-

related symptoms which hinder patients to participate and benefit from exercise

protocols (22).

Little is known about the specific effect of exercise interventions in the

psychological constructs implicated in the psychopathology of panic and whether the

observed gains are generalized or mediated by any of these variables. Along with that,

7
although laboratory research on exercise and anxiety present a more rigorous control of

physiological variables and exercise intensity (24, 25, 27), longitudinal studies fail in

present elucidative data on the cardiorespiratory changes and fitness condition before

and after participation and on the interactions between those variables and anxiety

symptoms improvement. Besides, exercise protocols reported to the moment include

general and unsupervised exercise prescriptions, with low direct control of exercise

intensity and of the cardiorespiratory and psychological parameters during sessions (30,

36, 37).

This study aimed to further understand the behavior and interactions between

several psychological and cardiorespiratory variables possibly implicated in using

exercise in the treatment of PD and raise hypotheses about the possible mediating role

of those parameters in the positive impact of exercise in the treatment of anxiety and in

reducing patients´ cardiovascular risk. Our hypothesis is that exercise might play a role

in promoting habituation to physiological cues, therefore directly influencing panic

symptom occurrence, as well as in enhancing physical health and fitness parameters

that could contribute to reducing patients’ cardiovascular risk.

Methods

Participants

The present study was approved by the Local Research Ethics Committee and

all participants signed an informed consent prior to participation. Patients with PD were

consecutively recruited in and outpatient psychiatry unit in the Panic and Respiration

Laboratory. Participants were diagnosed using a structured interview designed to

explore each of the necessary criteria for the main diagnoses of DSM-IV Axis I - the Mini

International Neuropsychiatric Interview (MINI) version 5.0, in order to assess present

psychiatric disorder and determine the possibility of inclusion in the study. Data

8
collection occurred individually and was performed by the same trained researcher.

Inclusion criteria were patients that met the DSM-TR criteria for PD and remained

symptomatic despite current medical treatment. Exclusion criteria comprised the

presence of relevant psychiatric comorbidity, current psychotherapy treatment and

medical conditions that counter indicate the participation in an exercise program.

Participants were examined by a psychiatrist and pharmacotherapy based on

antidepressants and/or benzodiazepines was naturalistic prescript or adjusted.

Prescription and dosage was maintained until the end of the study. Although depression

symptoms were not directed evaluated, mildly depressed patients with PD as the

primary diagnose were included.

Procedures

After agreeing to participate, patients went through a psychiatric screening

interview using the MINI and psychological evaluations. At the same day,

pharmacotherapy treatment was prescript and physiological evaluation was scheduled. If

patients were considered healthy by the Cardio Pulmonary Exercise Test (CPET), they

were consecutively allocated in pharmacotherapy + exercise (herein called exercise) or

pharmacotherapy-only groups. The consecutive design was chosen considering

logistical restrains in providing exercise training. The first 13 patients to enter the study

were consecutively allocated in the exercise group and the remaining 8 patients were

designed to the pharmacotherapy group. Psychological assessments were repeated

after 6 weeks and 12 weeks from baseline and CPET was repeated by the end of 12

weeks to evaluate possible cardio respiratory, morphologic and aerobic capacity

changes.

9
 Figure 1. Study design. Mini - The Mini International Neuropsychiatric Interview.

Psychological Evaluation

Subjects were requested to fill in the following self-report instruments: the Panic

and Agoraphobia Scale (PAS, (41)), the Anxiety Sensitivity Index (ASI, (42)), the

Agoraphobic Cognitions Questionnaire (ACQ, (43)) and the Body Sensations

Questionnaire (BSQ, (43)), the Cardiac Anxiety Questionnaire (CAQ, (44)) and the

Mobility Inventory for Agoraphobia (MI, (45)). The PAS is a 13-item rating scale

developed for measuring severity of panic symptoms and agoraphobia. The ASI is a 36-

item inventory that evaluates the extent to which a person believes that anxiety-related

sensations can be catastrophic. The ACQ has 14 items regarding thoughts that occur

when the person experiences anxiety. The BBS has 17 items and describes body

sensations that can potentially elicit anxiety. The CAD is a 14-item instrument designed

to evaluate how threatening the subject considers the experienced cardiac symptoms.

The MI is a 27-item inventory for the measurement of self-reported agoraphobic

10
avoidance and fear of specific situations.

Physiological Evaluation

Following psychiatric examination and psychological assessment, patients were

submitted to a physiological evaluation in order to assess cardio respiratory responses

to exercise and to ensure the safety of participation in the exercise protocol. Data on

anthropometrics, spirometry and electrocardiogram at rest were obtained prior to the

performance of the maximum CPET. Subjects were submitted to a maximum CPET in a

lower-limb cycle ergometer (Cateye EC-1600, Cateye, Japan or Inbrasport CG-04,

Inbrasport, Brazil), following an individualized ramp protocol targeting a duration

between 8 and 12 minutes. The load in watts was increased gradually until the patient

reached exhaustion, represented by the incapacity to continue to ride at the previously

established cycling frequency. Subjects were strongly encouraged by verbal stimuli to

reach the maximum effort during the CPET, and this only stopped when individuals

reached the maximum voluntary exhaustion. At this point, autonomic cardiac function

was evaluated and the maximum oxygen uptake (VO2max) was determined in order to

precisely inform the exercise protocol intensity. During the CPET, the exhaled gases

were collected by a Prevent pneumotachograph (MedGraphics, USA) coupled to a

mouthpiece, with concomitant nasal occlusion, and quantified by a VO2000 metabolic

analyzer (MedGraphics, USA), calibrated periodically by a 2-L syringe and gases of

known concentration. The metabolic analyzer enabled the quantification of pulmonary

ventilation and partial fractions of oxygen and carbon dioxide, expressed and analyzed

every 10 s. Following a standardization pattern, VO2 values were reported every minute

during the CPET, through the mean of six readings obtained during this period. Thus,

the value of the largest mean obtained referring to a given minute was considered the

VO2max (46). Before and after the CPET, patients were required to fill in the State-Trait

11
Anxiety Inventory – state anxiety (STAI) (47).

Exercise Protocol

Aerobic exercise training protocol consisted of 24 sessions, two times a week, in

a 12-week period. Each session encompassed 5 minutes of warm up walk, followed by

20 minutes of exercise (brisk walking in incline treadmill; INBRAMED Export 16 Plus) at

75% of the VO2max and 5 minutes of cool down walk. Exercise sessions were held

individually and supervised by a trained physical educator. In each exercise session,

heart rate (HR) was assessed before the session and every 5 minutes during exercise.

Subjects were also asked to rate their subjective perception of anxiety (Subjective Units

of Distress scale, SUDS (48)) and effort (BORG scale, (49)). SUDS range from 0 to 10

and BORG, from 6 to 20. Before and after each session, patients were required to fill in

the STAI.

Statistical Analyses

Friedberg analyses were used to evaluate the results at 6 and 12 weeks for each

of the subscales of the psychometric instruments, followed by Dunn's multiple

comparisons post hoc tests conducted to examine any significant changes between

moments. Comparisons between groups at baseline and final were held using Mann-

Whitney tests in both psychological and physiological variables. For changes between

baseline and final physiological evaluations, Wilcoxon analyses were performed. Data

analysis was conducted using SPSS® 17.0 for Windows and graphics were designed

using GraphPad (Prism).

RESULTS

Fifteen patients completed the study, 11 in the exercise group and 4 in the

12
pharmacotherapy group. Participants were 20% (n=3) men and 80% (n=12) women, with

median age of 45 years (31-48; interquartile limits). All patients were taking

benzodiazepines and 67% (n=10) took benzodiazepines associated with

antidepressants (imipramine, fluoxetine, citalopram, sertraline and venlafaxine). Eight

patients (53%) also presented depressive symptoms.

Psychological variables

When compared to baseline, patients who exercised along with

pharmacotherapy improved significantly regarding most subscales of the psychometric

instruments used. After 12 weeks of treatment, the exercise group presented less panic

symptoms, functional impairment, agoraphobic cognitions and health related anxiety

compared to the group that was only treated with medication. Mann-Whitney analysis of

the mean scores of the scales showed that groups were statistically indistinguishable at

baseline, except for the accompanied subscale of the MI (p=0.04) and the avoidance

subscale of the CAQ (p=0.02). Despite the observed improvement in the exercise group,

Mann-Whitney analysis did not find differences between groups in most of the subscales

after 12 weeks.

In the PAS, differences from baseline were observed in frequency and intensity

of PA (p=0.00), anxiety (p=0.01), impaired functioning (p=0.00) and health concerns

(p=0.00), but not in the agoraphobia and avoidant behaviors subscale (p=0.11). Dunn’s

Multiple comparisons test showed that most of the improvement was present by the end

of 6 weeks of exercise program, except for health concerns, that improved more sharply

between 6 and 12 weeks of treatment. Patients only taking medication did not show

significant differences from baseline in any of the subscales.

13
Figure 2. PAS subscales scores represented as median with interquartile range. PAS – Panic and Agoraphobia Scale.

The same tendency was observed in the CAQ. Mean scores of the exercise

group dropped after treatment, when compared to baseline (fear and hypervigilance

p=0.00 and avoidance p=0.00). Multiple comparisons showed that CA decreased more

intensely between 6 and 12 weeks of treatment for all subscales. Patients in the

pharmacotherapy group did not change after 12 weeks.

Figure 3. QAC subscales scores represented as median with interquartile range. CAQ – Cardiac Anxiety Questionnaire

Also in the BSQ, exercise group yield lower scores after treatment (p=0.00) while

pharmacotherapy group scores remained unchanged. In the exercise group, most of the

decrease in BSQ scores was achieved by 6 weeks of exercise program.

14
Figure 4. BSQ subscales scores represented as median with interquartile range. BSQ – Body Sensations Questionnaire.

In the ACQ, participants from the exercise group had significantly lower scores

after treatment in both subscales (lack of control p=0.01 and physical concerns p=0.02),

with the more expressive occurring between 6 and 12 weeks of treatment.

Pharmacotherapy group patients also improved significantly in the physical concerns

subscale after 12 weeks (p=0.04).

Figure 5. ACQ subscales scores represented as median with interquartile range. ACQ – Agoraphobic Cognitions

Questionnaire.

In the MI, the most relevant difference was observed when patients where

unaccompanied in the feared situations. Patients from the exercise group significantly

improved their levels of anxiety after the exercise program, compared to baseline

(p=0.01), while the participants only treated with medications did not report any change.

Mann-Whitney tests of mean scores showed a significant difference between groups

after treatment (p=0.03) that was not present at baseline. The more impacting change in

15
anxiety levels was reported between 6 and 12 weeks. On the other hand, both groups

improved in anxiety in feared situations when accompanied over the 12 weeks of study

(exercise p=0.00 and pharmacotherapy p=0.00), also with the more relevant change

between 6 and 12 weeks of treatment. At baseline, pharmacotherapy only patients had

higher scores of anxiety when accompanied in the feared situations compared to the

exercise group (p=0.04) and this difference disappeared after 12 weeks.

Figure 6. MI subscales scores represented as median with interquartile range. MI – Mobility Inventory for Agoraphobia.

In the ASI, both groups yield lower levels of AS after 12 weeks concerning the

total score (exercise p=0.00; pharmacotherapy p=0.04), fear of cardio respiratory

(exercise p=0.00; pharmacotherapy p=0.04) and gastric (exercise p=0.00;

pharmacotherapy p=0.04) symptoms. Exercise patients also significantly improved in the

fear of losing cognitive control (p=0.00) and of public displays of anxiety manifestations

(p=0.00) after the exercise program. In this group, most of the change occurred between

6 and 12 weeks of participation, whereas in pharmacotherapy group, the most relevant

improvement occurred in 6 weeks. Even though both groups had improved over time, by

the end of 12 weeks, the exercise group scores were significantly lower than

pharmacotherapy-only patients only in the fear of losing cognitive control factor (p=0.04).

No differences were observed between groups at baseline and final evaluations of the

three other subscales.

16
Figure 7. ASI subscales scores represented as median with interquartile range. ASI – Anxiety Sensitivity Index.

Levels of anxiety were also assessed throughout the 24 sessions in the exercise

group. Subjective perception of anxiety, measured through the SUDS before and after

each section, demonstrated that anxiety levels before session significantly decreased

over time from 3,45 at baseline to 1.81 (p=0.00), with no difference between the baseline

and 6 weeks and 6 weeks until final. The same was observed with subjective anxiety

levels after each training session (p=0.00), that varied from 2.00 at baseline to 0.90, by

the end of 12 weeks. Anxiety levels after session dropped more intensely in the first 6

weeks, but this tendency presented no statistical significance in this sample (p=0.06). In

the second exercise section, a peak level of pre and post anxiety was observed, but

means scores started decreasing thereafter.

17
Figure 7. Anxiety scores during exercise sessions represented as median and interquartile range. SUDS – Subjective

Units of Distress Scale. CPET – Cardiopulmonary exercise test.

Trait anxiety significantly decreased over time, with no specific relevant period of

change (p=0.00). A slight raise was also observed in the first sessions, decreasing

thereafter. No difference was found, however, in state anxiety before session from

baseline to 12 weeks (p=0.06). On the other hand, state anxiety after exercise section

significantly improved with treatment (p=0.00), with the most expressive, although not

significant, decrease observed from 6 to 12 weeks (p=0.17). State anxiety was also

measured before and after each CPET (baseline and final). In both baseline and final

assessments state anxiety significantly decreased after test (p=0.00 and p=0.03,

respectively). Also, a significant improvement in state anxiety levels before the test was

observed comparing baseline and final evaluations (p=0.00), but not after test. Table 1

provides details on the comparative analysis of the anxiety subscales between groups

18
over 12 weeks of treatment.

PAS - Panic and Agoraphobia Scale; ASI - Anxiety Sensitivity Index, ACQ - Agoraphobic Cognitions Questionnaire, BSQ -

the Body Sensations Questionnaire; CAQ - Cardiac Anxiety Questionnaire; MI - Mobility Inventory for Agoraphobia

Physiological variables

Each one of the patients allocated to exercise intervention group performed 30

19
min of individualized treadmill exercise distributed in 24 sessions, comprising a total of

12 hours of aerobic type of activity. HR monitoring during exercise sessions indicated

that for the vast majority of sessions, patients’ exercising HR was kept in the proposed

target zone, corresponding to about 75% of maximum VO2 and representing an effective

aerobic training load. No clinical complications occurred during the exercise sessions.

A total of 32 successful maximal CPETs were performed in 18 patients, with 14

of them being assessed twice, at baseline and after completing either the 12-week

exercise intervention program or the pharmacotherapy only protocol. No differences

were found between groups at baseline. Three of the drop out patients were also tested

in baseline and showed no differences from the other participants in the tested variables.

No clinical or electrocardiographic abnormalities were found that required earlier CPET

termination. The obtained maximum HR corresponding was, in median, 92% of age-

predicted value (50) and was about identical for both exercise and pharmacotherapy

only patients (p=0.98).

Along the 12-week period of the study, patients in exercise group have not

significantly changed their major morphological characteristics, as evaluated by body

weight (p=0.13), sum of six skinfolds (p=0.36) and abdominal girth (p=0.50). Both

exercise and pharmacotherapy groups have not had significant resting HR or blood

pressure changes after 12-week period. While modest changes were seen due to

exercise intervention at some of submaximal CPET variables, e.g., median 10%

increase in VO2 and workload at anaerobic threshold exercise intensity, these gains

were not significant.

At maximal exercise intensity, however, substantial improvements could be found

in exercise intervention group. While no changes could be seen in major hemodynamic

variables, such as maximum values of HR (p=0.62) and systolic (p=0.41) and diastolic

(p=0.31) blood pressure, maximum expired ventilation and all aerobic performance

20
indicators were significantly improved (p<0.05). Consistent with the low baseline values,

% of age-predicted maximum VO2 increased 18% (63 to 74%) corresponding to an

improvement of 3.8 mL.kg-1.min-1 or 1.1 METs (p=0.04). By using the same initial and

incremental workload rate, patients in the exercise group were able to tolerate two more

minutes of effort at the CPET (8 to 10 min; p=0.01), while patients that were not

physically trained had identical durations in both CPETs (9 min). Table 2 summarizes

the most relevant results obtained at CPET for both groups at baseline and after 12

weeks of the study.

21
 VO2 - maximum oxygen uptake ; VE - maximum expired ventilation

Discussion

As expected, the positive role of exercise training in symptom reduction in

addition to traditional pharmacotherapy treatment to PD found in this study is consistent

with previous reports in the literature (34). Surprisingly, no differences were observed

between pharmacotherapy and pharmacotherapy + exercise in most of the subscales

after 12 weeks, contrary to other research reports that point to a superior effect of the

combination of regular therapy with exercise (34, 36).

Intra-group comparisons over the 12-week period, however, presents a more

clear interpretation of the results, showing a significant effect in symptom reduction of

the combination with exercise over time, which was not present in most of the variables

studied in the pharmacotherapy group. This behavior is consistent with another study of

combination of exercise and drugs in which, despite the absence of significant

differences between groups by the end of the investigation, intra-groups positive effects

were observed (34). The present outcomes point to an incremental role of exercise and

suggests its usefulness as an adjunct therapy to be added to already established

interventions such as pharmacotherapy and CBT in the treatment of PD (19, 36).

Our research design provides interesting information on the behavior of several

variables implicated in the psychopathology of PD and sheds light on the specific effect

of exercise in each of these variables. In this sense, results clearly point to an early (by 6

weeks) and more expressive effect of exercise in the psychological aspects related to

anxiety concerning physiological arousal, body symptoms and interoceptive conditioning.

This can be seen in the PAS, where differences from baseline were observed in

frequency and intensity of PA, anxiety, and functioning and in the general fear of body

sensations (BSQ). These results confirm the original prediction of a potential role of

exercise in promoting habituation to physiological cues, similarly to the effect of

22
interoceptive exposure techniques (19, 22, 23).

The impact of exercise in the frequency and intensity of PA and anxiety is also in

coincidence with the reported anti panic effect of exercise in laboratory settings (24, 26,

27). As reported, the neurophysiologic changes due to exercise (29, 42), promote an

immediate anti panic modulation, as patients can experience autonomic arousal induced

by exercise in the absence of panic or in the presence of more attenuated anxiety

reactions (24, 26, 27). In this sense, exercise could have an additional advantage over

regular interoceptive exposure in terms of the intensity of symptoms that can be elicited

without panic reactions, which possibly potentiates habituation. Immediate anxiolytic

effect of exercise could also be seen within exercise session, with SUDS decreasing

after session termination. The same behavior was observed in state anxiety after

maximum exercise test (CPET). In-session and over time decrease in SUDS reported by

patients, with maintenance of intensity of effort controlled by the assessment of HR, also

speak for the habituation effect of exercise.

After 12 weeks, more specific health-related fears are impacted by exercise

training, such as the CA subscales and the AS subscales concerning fear of cardio

respiratory, gastric and cognitive symptoms. We could hypothesize that the variables

that include cognitive information processing, like restructuring of health-related worries

and fears and agoraphobic cognitions could suffer an indirect impact of exercise,

possibly through naturalistic evidence of safety provided by the previous reduction in

panic symptoms and fear of body symptoms. This is consistent with the smaller and

latter effects of the exercise program in health and physical concerns and agoraphobic

cognitions.

As agoraphobia is operationally defined in the psychometric instruments used as

cognitions about the threatening potential of experienced body symptoms and behavioral

avoidance of feared situations (mobility), is was expected that no significant impact of

23
exercise could be observed. Exercise in this study seem to have a more relevant effect

on anxiety reduction through habituation to physiological arousal, and only an indirect

impact in cognitive agoraphobic processing. This effect is similar to the observed

immediate effect of psychotropic drugs, which only indirectly affect agoraphobia after

reduction in panic symptoms (51). In the gold-standard treatment of PD, agoraphobia is

more effectively addressed by CBT, with cognitive restructuring and situational exposure

techniques (52, 53). As none of these therapeutic strategies were used in this study, the

observed absence of consistent effect on agoraphobia was expected.

The behavior of AS subscales reported here was consistent with previous studies

that showed a specific impact of exercise in reducing AS (6, 40). Analysis of subscale

scores showed that, interestingly, not only fear of cardio respiratory symptoms, directly

elicited by aerobic exercise, but also fear of less specifically-related to exercise

symptoms such as gastric and cognitive symptoms were also impacted. This finding

speaks for a unspecific secondary effect of exercise in the fear of body symptoms, which

is contrary to the current idea that interoceptive exposure should be focused on the

feared symptom domain and similar to the feared somatic manifestation to be effective

(54, 55). This issue, however, deserves further studies for clarification.

Despite the significant observed effect in AS, our study enhances the discussion

whether it is the single underlying mechanism through which exercise positively impacts

the treatment of PD (13). Our data suggest that, despite the clear impact of exercise in

AS, it does not seem to present any distinct effect on AS when compared to the other

measures of fear of body symptoms. Thus, it is likely that habituation to physiological

arousal, potentiated by the anti panic effect of exercise reduces the occurrence and the

fear of involuntary somatic manifestations with a further impact on health and symptom-

related anxiety plays a mediating role in the observed positive effects of exercise in PD

patients.

24
 To further understand the selective role of exercise in each of the relevant

aspects of psychopathology of PD was the aim of this study and was only possible by

analyzing the scores of the subscales of the instruments used. Our outcomes shed light

on the possible underlying mechanisms of the observed positive role of exercise in the

treatment of PD. It is interesting that exercise does not seem to generally affect the

symptoms, but rather present a selective specific effect of some aspects of its

psychopathology. It is probably due to this selective effect that exercise does not present

satisfactory outcomes when provided alone, in comparison to established therapy (30,

37) , but seems to play and important role as a adjunct tool in the treatment (34, 36).

Although there were no major changes in morphological characteristics or in non-

aerobic components of physical fitness, in physiological terms, the major finding of the

study was that a period of a relatively simple and short aerobic exercise training

intervention (12-hour of exercise in total or one hour/week) was well tolerated and able

to induce significant improvements in several indicators of maximal performance in the

group of 11 patients. Gains ranging from 10 to 20% were observed in test duration,

maximum workload and VO2 maximum, bringing their results closer to age and gender-

predicted values for healthy peers, which may positively reflected in their physical health.

As indicated by Meyer et al (56), low fitness observed in PD patients seem to be

a byproduct of physical activity avoidance, and can be directly impacted by exercise

interventions aiming to achieve non-clinical control levels. Contrary to outcomes reported

by this author, that found no association between improvement in fitness and changes in

psychopathology measures, the present study found that the psychological improvement

was accompanied by enhanced fitness capacity.

As reduced fitness capacity is directly associated with a higher all-cause mortality

(57) and increased cardiovascular risk (58) in healthy subjects, the inclusion of an

exercise protocol in the treatment of PD can, per se, be useful as a cardio protective

25
strategy for those patients. Moreover, recent cohort studies found that PD is a significant

independent risk for new onset coronary heart disease, acute myocardial infarction, and

cardiac mortality (19, 59, 60). One of hypothesis is that a sedentary lifestyle and it´s

metabolic consequences might mediate this association (see Sardinha et al (19) for

details). In this sense, it is possible that exercise plays a double role in the treatment of

PD: psychological symptoms and cardiovascular risk reduction.

Acknowledgements

Authors would like to thank Clínica de Medicina do Exercício (CLINIMEX),

particularly Dr. Claudia Lucia Castro and Dr. João Felipe Franca, who performed the

CPET, and the Panic and Respiration Laboratory psychiatry team, for patients´ referral.

This study was founded by CNPq, INCT-TM (CNPq) and FAPERJ.

26
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34
Artigo 7:
Sardinha A, Araújo CGS, Nardi AE. Treinamento físico intervalado como ferramenta
na terapia cognitivo-comportamental do transtorno de pânico. J Bras Psiq.
2011;60:227-30.

95
Conclusões

Os resultados dos estudos apresentados nesta tese representam um avanço

importante na integração entre as intervenções terapêuticas medicamentosas e
cognitivo-comportamentais e a saúde geral dos pacientes com TP. A recomendação
sistemática da prática de exercícios físicos pode ser usada, no contexto da TCC,
tanto como uma potencial ferramenta para a exposição interoceptiva, quanto para
fins de reestruturação cognitiva das crenças relacionadas à vulnerabilidade aos
sintomas físicos. O avanço das pesquisas nesse ainda insipiente campo do
conhecimento visa ainda clarificar a relação entre sintomas associados ao pânico,
como a evitação fóbica, a sensibilidade à ansiedade e a ansiedade cardíaca e a
manutenção de um estilo de vida pouco saudável, ao sedentarismo e à síndrome
metabólica, nos pacientes com TP.
A partir disso, será possível avançar na compreensão dos aspectos
psicológicos que intermediam tal relação, permitindo o desenvolvimento de
estratégias cognitivo-comportamentais especificamente voltadas para sua
modificação. Uma vertente de estudo derivada desta linha de pesquisa poderia ter
como objetivo elaborar e testar a eficácia de estratégias cognitivo-comportamentais
especificamente voltadas para potencializar a adesão do paciente com sintomas de
estresse, ansiedade e depressão a um programa de exercício físico. Resultados
positivos poderiam beneficiar não apenas pacientes com TP, mas também
cardiopatas com níveis elevados de ansiedade cardíaca e ansiedade relacionada à
saúde, além de indivíduos com sintomas psicológicos de ansiedade, estresse e
depressão, mas ainda saudáveis do ponto de vista psiquiátrico e cardiovascular, a
reduzir seu risco cardiovascular e manter a saúde física através da prática regular de
exercícios físicos.
A linha de pesquisa com exercícios físicos, iniciada pela autora no Laboratório
de Pânico e Respiração em 2009, tem ainda muitas fronteiras a serem exploradas
em estudos futuros. O presente estudo pode ser considerado um ensaio preliminar
da viabilidade da proposta de utilizar exercícios nos tratamento do TP, tanto em
termos de resultados quanto em termos da segurança e logística dos procedimentos
adotados. A opção de seguir os pacientes por um tempo maior do que o que se
encontrava até então na literatura e o uso de diversos instrumentos psicométricos e
fisiológicos cuidadosamente medidos nos permitiu realizar um primeiro levantamento
100
de que variáveis precisam ser melhor estudadas para se compreender os
mecanismos através dos quais o exercício contribui para a redução da ansiedade.
Entretanto, esta opção teve um impacto negativo importante sobre a adesão
dos pacientes ao estudo, com muitas desistências ao longo do caminho (drop outs).
Isso foi especialmente relevante no grupo que tomava apenas medicação, uma vez
que os pacientes estavam sintomáticos no início do estudo e não tiveram
modificações em seu tratamento farmacológico durante a pesquisa. Para este grupo,
os diversos momentos de medidas psicométricas e, principalmente, fisiológicas,
foram considerados desagradáveis, já que eliciavam ansiedade e não geravam
melhora significativa do quadro clínico.
Além disso, não foi possível estudar diretamente a aplicação do protocolo de
exercício físico no contexto da TCC no estudo com o protocolo de exercício aeróbico
contínuo, apenas no caso relatado no artigo 7. No artigo 6, foram observadas
mudanças indiretas em variáveis com maior mediação cognitiva, como as cognições
agorafóbicas e a ansiedade cardíaca, nos pacientes que participaram do programa
de exercícios, mas não se pode afirmar ainda se o tratamento concomitante com
TCC poderia gerar benefícios específicos, como foi aventado no caso relatado.
Em relação aos pacientes cardiopatas com TP, a partir dos resultados dos
estudos transversais (artigos 4 e 5) que mostraram que os pacientes que praticam
exercícios tem um perfil diferente dos que não praticam em relação à prevalência de
transtornos mentais e de ansiedade relacionada à saúde, pode-se hipotetizar que os
exercícios teriam um papel importante no tratamento e redução do risco
cardiovascular nestes casos. Entretanto, tanto o protocolo de exercício aeróbico
contínuo (artigo 6) quanto o protocolo de exercício aeróbico intervalado (artigo 7)
não foram testados em pacientes cardiopatas. Assim, é necessário ter cautela na
extrapolação dos resultados obtidos e na aplicação desta proposta para tal
população, principalmente levando em consideração aspectos relativos à segurança
da prática de exercícios em cada caso. O exercício prescrito e supervisionado por
médicos poderia ser uma opção para esses pacientes.
Uma vertente de estudos ainda insipiente que foi derivada desta linha de
pesquisa, já com alguns estudos em fase de produção, é a aplicação dos
conhecimentos do papel da ansiedade na prática de exercícios e dos mecanismos
da ansiedade cardíaca para aprimorar os procedimentos do Teste Cardiopulmonar

101
de Exercício (TCPE) para pacientes com ansiedade. Ao longo dos X testes
realizados, diversas observações foram feitas sobre comportamento e no impacto da
ansiedade durante o exame. Atualmente, estão em teste a validade da utilização de
alguns parâmetros fisiológicos submáximos e a aplicação de estratégias de manejo
da ansiedade ao longo do teste, de modo a obter resultados mais acurados no
TCPE de pacientes com ansiedade.
Por último, a integração da dos conhecimentos da psicoterapia cognitivo-
comportamental no contexto mais amplo da saúde promoverá ainda uma
aproximação do psicoterapeuta com os demais integrantes da equipe de saúde, no
caso, os médicos, nutricionistas e os profissionais de educação física. É possível
que o trabalho multidisciplinar integrado possa contribuir para o aprimoramento da
saúde e da qualidade de vida dos pacientes de maneira mais eficaz do que a soma
das intervenções específicas isoladas.

102
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