Smoking Hypertension CPD 2011 Art 2

Current Pharmaceutical Design, 2011, 17, 2987-3001
Smoking and Hypertension: Effects on Clinical, Biochemical and Pathological

Variables Due to Isolated or Combined Action on Cardiovascular System
Linda Landini and Aurelio Leone*
Department of Internal Medicine, University of Pisa, Italy; *Fellow of the Royal Society for Promotion of Health, London, UK
Abstract: Changes in clinical, biochemical and pathological variables characterize cardiovascular damage from smoking and hypertension when it acts independently. However, combined action of these major risk factors increases the rate of cardiovascular events.
Ischaemic heart disease with stable effort angina, myocardial infarction and post-infarction arrhythmias may affect cardiovascular system
because of smoking exposure. Among cerebrovascular disease, there is evidence that stroke would be related primarily to active smoking.
Isolated hypertension plays significantly major action to cause cerebrovascular disease including stroke, recurrent stoke and transient
ischaemic attack. Among cardiac events, heart failure is, often, the end-point of hypertensive disease, even if manifestations of ischaemic
heart disease similar to those caused by smoking may be increased in rate.
Combined action of smoking and hypertension usually increases the rate of cardiovascular complications and leads to a progression of
atherosclerosis with narrowing and plaque primarily at the the level of coronary, carotid and cerebrovascular arteries. A pattern specific of
both active and passive smoking exposure, but not hypertension, is the thromboangiitis obliterans that dramatically worsens in continuing smokers while it can be improved by stopping smoking.
Keywords: Smoking, hypertension, combined action, cardiovascular system.

Large population findings
have demonstrated that the rate
INTRODUCTION
of cardiovascular disease in
smokers statistically increased
Smoking and hypertension are two major risk factors for car- in absence of other major
diovascular disease [1].
cardiovascular risk factors.
Many reports identify cardiovascular system as one of the ma-jor Therefore, smoking may be
target organs for smoking [2-12]. Both active and passive smok-ing considered as an independent
factor
for
both
damage the heart and blood vessels although pathological mechanisms risk
may differ for type of action but not chemical toxics of which cause cardiovascular disease and
the alterations [13-30]. In addition, changes in blood pressure, events, although the risk is
whatever responsible cause there is, influence heavily cardiovascular closely dependent on several
variables
related
to
function and structure [32].
characteristics of smoking as
No unanimous opinion exists on the relationship between smok- well as individu-als health.
ing and hypertension with regard to their association in cardiovas-cular
damage.
Adverse effects of tobacco
smoke are the result of some
Some authors [33-34] support the hypothesis that there is only a
limited association between hypertension and smoking while others chemi-cals usually concentrated
[22-29] underline a strong association. Some others then [14,35,36] and condensed into tobacco
emphasize the role of smoking on the cardiovascular system either mixture, par-ticularly when the
independently or by increasing the harmful effects of other risk fac- mixture is burning [23]. Of the
tors including hypertension. In addition, the age of smokers and more than 4,000 chemicals of
burning tobacco, only a few
duration of smoking habit could influence the blood pressure.
participate
actively
to
The purpose of this review is to describe clinical, biochemical and cardiovascular damage, since a
pathological effects of both smoking and hypertension as inde-pendent large majority of them has
and combined risk factors for cardiovascular system.
carcino-genic effects. However,
those chemical compounds able
SMOKING AND CARDIOVASCULAR SYSTEM
to damage heart and blood
Commonly, smoking is the inhalation of the smoke of burningvessels have a high toxicity of
tobacco of cigarettes, pipes or cigars. However, epidemiological and either acute or chronic type.
statistical reports analyse primarily the effects of cigarette smoking. That, undoubtedly, increases the
Clinical, biochemical and pathological factors [36] interact to lead rate of morbidity and mortality
cardiovascular
events.
to a strong harm of cardiovascular system. In addition, they may be for
also a consequence of smoking exposure. Some body or-gans like Deaths and disability due to
lungs, heart and blood vessels, epithelial glands, and brain are a target cigarette smoking are currently
continuously reaching
of smoking toxics. Both active and passive smoking play a significant and
values that modify the concept
role to cause cardiovascular damage.
of epidemiological transition
just described in a review of this
*Address correspondence to this author at the Via Provinciale 27, 19030 issue [37-38].
Castelnuovo Magra (SP), Italy: Tel/Fax: +390187 676346;
E-mail: reliol@libero.it
them as old as fewer 70 years.

In addi-tion, more than one third
of current smokers meet partial
or perma-nent disability, which
is responsible for enormous
costs to public health.
Both active and passive
smoking have almost the same
adverse
effects
on
cardiovascular system, although
they are differently dated in
time and with a few different
characteristics.
Tobacco Smoke Compounds
Three chemical compounds
of smoking have been, for a
long time, recognized able to
damage cardiovascular system:
nicotine and its metabolites,
carbon
monoxide
and
thiocyanate. However, there is
an increased evidence [39-40]
that ammonia, benzene and
some carcinogens play an
evident effect on changes in
heart and blood vessels. Table 1
reports the main chemicals that
may
affect
cardiovascular
system as well as the other body
structure involved.
Carcinogens act primarily
throughout two mechanisms:
exert-ing effects, which increase
the damage induced by nicotine,
and stimulating the action of
carbon monoxide.
Worldwide, more than 3

million people [24-25] die each
year for smoking, being half of
1381-6128/11 $58.00+.00
2011 Bentham
Science Publishers
2988 Current Pharmaceutical Design, 2011, Vol. 17, No. 28
Table 1. Tobacco Chemicals Damaging Cardiovascular System

and Other Body Organs
Chemical
Structure
Nicotine
Sympathetic system, Vascular bed,

Heart, Adrenergic system
Carbon monoxide
Arterial wall, Myocardium
Thiocyanate
Thyroid metabolism, Blood vessels

Myocardium
Ammonia
Blood vessels
2-naphtylamine
Blood vessels
Benzo-anthracene
Benzo-pyrene
Nicotine [41-42] is an alkaloid that constitutes approximately

0.63.0% of the dry weight of tobacco. Fresh leaves of nicotine
have high toxicity in both animals and humans with specific effects
involving insects and harvesters since nicotine biosynthesis occurs
in the roots and leaves. In low concentrations (an average cigarette
yields about 1 mg of absorbed nicotine), the substance exerts stimulant and addictive effects. According to the 1988, Surgeon General's Report [43], cigarettes and other forms of tobacco are addicting; nicotine is the drug that causes addiction; pharmacological and
behavioural characteristics that determine tobacco addiction are
similar to those of heroin and cocaine.
Nicotine can be dosed in blood plasma or urine to confirm a
diagnosis of poisoning or smoking exposure. Urinary or salivary
cotinine, the main metabolite of nicotine, is frequently measured for
the screening of smoking habit as well as for purposes of preemployment and health insurance. In addition, a correct interpretation of the results is important, since passive smoking exposure can
also determine a significant accumulation of nicotine or its metabolites in various body fluids [44-45]. Nicotine, entered the blood,
acts on the nicotinic acetylcholine receptor specifically the ganglion
type nicotinic receptor and one CNS nicotinic receptor. The former
is present particularly in the adrenal medulla, while the latter is present in the central nervous system (CNS). In small concentrations,
nicotine increases the activity of these receptors. In addition, nicotine has effects on a variety of other neurotransmitters closely
stimulating those structures currently involved for the control of
blood pressure and other functional heart parameters, primarily
heart rate [46]. Indeed, there is evidence that nicotine has very
powerful effects on arteries, raises blood pressure and is also a
vasoconstrictor, which adversely influences heart pump function.
Finally, nicotine, after its stimulating effects, undergoes a phase
of depression that can vary in the time for duration, but, usually, it
is transient although prolonged.
Carbon monoxide is a gas quickly absorbed into the blood and,
then, it reduces blood capacity to carry oxygen. Inhalation of carbon monoxide has the same effects on active or passive smoking
since the result depends on the concentrations reached by the gas
into the blood [17]. Carbon monoxide toxicity is primarily due to
the strongest bond with haemoglobin with production of carboxyhaemoglobin. The bond of haemoglobin with carbon monoxide is
about 400 times stronger than that with the oxygen. In addition, the
gas exerts a directly detrimental action on the heart and blood vessels by affecting heavily either myocardium or arterial wall at various levels including particularly coronary, carotid and cerebrovascular arteries. Blood concentrations of carboxyhaemoglobin are re-
Landini and Leone
lated to carbon monoxide inhaled smoking cigarettes or that

breathed from burned cigarettes into the environment.
The mechanism of carbon monoxide toxicity involves four
stages [47]: removing oxygen from oxyhaemoglobin, bond between
haemoglobin and the gas with lack to carrying out the oxygen, hypoxia of body tissues and impairment of intracellular chains deputed to respiratory metabolism. Thus, aerobic metabolism is heavily damaged with marked reduction or loss of functional responses
of involved body structures [48-52].
The symptoms of toxicosis as well as the degree of organ damage depend primarily on the percent concentration of carboxyhaemoglobin into the blood.
Biochemical monitoring of carbon monoxide inhaled either
from cigarette smoking or passive smoking exposure may be assessed by the dosage of blood carboxyhaemoglobin. However, the
dosage of carbon monoxide coming from smoking is difficult to be
established because of a large amount of carbon monoxide derived
from industries, car fuel and other machineries acting as environmental pollutant.
Experimental findings [53] conducted on non-smoker individuals exposed to passive smoking measured carboxyhaemoglobin levels before and after exposure. In addition, dosage of carboxyhaemoglobin can be made in an arterial or venous blood sample, although the estimated value cannot be totally attributed to cigarettes
smoked. Usually, the concentration of carboxyhaemoglobin following acute exposure to passive smoking up to a carbon monoxide
concentration 30-35 ppm/air increases from twice to four times the
value detected before exposure [53].
Thiocyanate is the third smoking chemical able to induce cardiovascular damage, although with a lower power than that of nicotine and carbon monoxide. Instead, thiocyanate increases the damaging effects of both those chemicals. Evidence indicates that active
and passive smokers have a mean blood thiocyanate concentration
0.4 mcg/ml.
Thiocyanates are a group of chemical compounds that have
toxic effects on several body organs [54-56]. They inhibit mitochondrial ferricytochrome oxidase and other enzymatic chains and
hence block electron transport. A reduced oxidative metabolism and
oxygen utilization is the result of these mechanisms. Thus, there is
an impairment of cellular respiratory chain with tissue hypoxia or
worsening the degree of pre-existing hypoxia.
Burned tobacco commonly releases thiocyanates which
increase their blood concentrations in individuals exposed to
smoking.
There are some foods like milk, almonds, garlic, onion, leek,
cabbage and cauliflower which contain thiocyanates. Such a fact
makes hard to dose the exact amount of the thiocyanate produced
by burned cigarettes in smokers. In addition, monitoring serum
thiocyanate is more expensive than that of nicotine and cotinine
currently used to assess smoking habit. However, thiocyanate
causes cellular hypoxia, which strengthens that due to both carbon
monoxide and nicotine.
Carcinogens have been recently identified chemical compounds
able to damage cardiovascular system [36] because of a direct action on cellular components. However, their action on heart and
blood vessels is poor when compared to the damage of respiratory
system and other body organs.
In conclusion, the toxic effects of tobacco smoke compounds
are primarily due to carbon monoxide and nicotine, whereas the
other chemicals exert same effects of very limited power. Fig. (1)
shows the percent importance of the different tobacco chemicals
involved in cardiovascular damage according to their power, as reported by the literature on the subject.
In addition, it is worthy noting that carbon monoxide always
causes a morphological damage that leads, in time, to irreversible
Smoking and Hypertension
Current Pharmaceutical Design, 2011, Vol. 17, No. 28 2989
Carbon Monoxide
97%
Nicotine
95%
Thiocyanate
Carcinogens
45%
8%
100%
Fig. (1). Smoking chemicals primarily involved in cardiovascular damage. Carbon monoxide, the most dangerous chemical of smoking, exerts both a direct
action on cardiovascular system and adverse effects on some cardiovascular parameters. It is closely followed by nicotine.
Table 2. Main Clinical

Patterns in Active and Passive
lesions of cardiovascular system as well as the appearance of non-fatal
Smokers
and fatal cardiovascular and cerebrovascular events.
Clinical Variables
The analysis of the data provided mainly by observational study
allows identifying some clinical patterns specifically related to
cigarette smoking.
Clinical damage involves primarily those individuals who have
other major cardiovascular risk factors associated with cigarette
smoking. Among these factors, high LDL-Cholesterol concentra-tions
and hypertension play a strong role. Symptoms related to an-gina
pectoris, myocardial infarction, arrhythmias, stroke or recur-rent stroke
occur with higher rate [10-16, 26, 57-61]. Table 2 shows the main
clinical patterns related directly or mediated by other func-tional or
pathologic parameters to cigarette smoking.
1. Active smokers
concentrations,
while
the
subjects with a pre-vious
myocardial infarction had all
studied parameters heavily impaired. In addition, individuals
Ischaemic
disease
withheart
pre-existing
myocardial
infarc-tion
documented
ventricular arrhythmias, which
needed to stop ex-ercise in
some of them [10]. Pimm et al
[63] analysed twice the response to exercise of 20 healthy
young men and women in a
free-smoking environment and
in an environment
polluted by
Cerebrovascular
disease
carbon
Clinical damage is often associated with other types of damage

caused by smoking exposure including functional and pathological
manifestations. In addition, clinical damage may worsen an underlying cardiovascular disease.
Some characteristics can identify the damage caused by ciga-rette
smoking.
Hypertension
Atherosclerosis
Coronary heart disease associated with clinical symptoms may be

Systemic artery disease
the result of a large number of pathologic factors including in-creased
blood carboxyhaemoglobin, diminished oxygen transport, enhanced
platelet adhesiveness and aggregation, and impaired car-diac
performance. These factors, primarily due to a combined ac-tion of
carbon monoxide and nicotine, exacerbate, in the long end, the 2. Passive smokers
atherosclerotic process [62]. Effort angina often accompanies both
smokers and non-smokers exposed to passive smoking [8]. A clear
worsening of clinical manifestations and appearance of chest pain
during exercise at a lower threshold level may, usually, be seen.
Authors analysed the performance to exercise of 10 men with stable
Cerebrovascular disease
effort angina. The men underwent exposure to environmental tobacco
smoke twice: in a smoke-free environment and in an envi-ronment
Hypertension
polluted by carbon monoxide. Exposure to passive smok-ing induced
Atherosclerosis
an increase in heart rate, blood pressure, and carboxy-haemoglobin
concentrations and a statistically significant decrease of threshold
Peripheral artery disease progresangina equal to 22% during smoking exercise. Im-paired cardiac
sion
performance in both healthy and subjects suffering from pre-existing
myocardial infarction was also documented dur-ing passive smoke
exposure by Leone et al [53]. Nine healthy sub-jects and 10 with a carboxyhaemoglobin level, and
previous myocardial infarction, who were tested and controlled, level of expired carbon
performed the same exercise on a bicycle ergometer twice: in a smoke- monoxide. In a smoking
free environment and, then, in the same environ-ment polluted by 30 environment, healthy subjects
to 35 ppm/air carbon monoxide arising from burning cigarettes. showed a statistically prolonged
Analysed parameters of the study were the peak of exercise power, time to recovery of pre-exercise
time to recovery of pre-exercise heart rate,
heart rate and increased
carboxyhaemoglobin
monoxide at a concentration of 24 ppm/air. Exercise on a bicycle
ergometer lasted 7 minutes. In a smoking environment, there was a
significant increase in carboxyhaemoglobin not associated with

other functional disorders of cardiovascular system. Finally,
McMurray et al. [64] reported that the exercise of eight healthy individuals, 4 smokers and 4 non-smokers, reduced its duration in
passive smoke environment. Finally, other two studies [65-66] analysed the exercise tolerance of individuals with a history of ischaemic heart disease. Both these findings documented appearance of
clinical signs of myocardial ischaemia and ventricular arrhythmias
when carbon monoxide concentration was elevated in the exercise
environment.
There is evidence that the effects of smoking compounds on
cardiovascular system may be better identified by experimental
studies conducted in passive smoking exposure since, clinically,
they allow to establish those changes of analysed parameters due to
the concentrations of carbon monoxide in the environment where
the experiment is performed. Indeed, it is very difficult to attribute
clinical symptoms of smoker or non-smoker individuals passively
exposed to smoking since the symptoms that characterize ischaemic
heart disease are similar to both groups as well as in never smokers.
However, a significant impairment of the signs of myocardial
ischaemia was, undoubtedly, documented by experimental findings.
The characteristics of sudden cardiac death need some considerations. Clinically, life-threatening ventricular arrhythmias as well
as sympathetic or adrenergic stimulation, mainly due to the action
of nicotine, play primarily a pathogenic role which determine functional responses. [67-68]. A direct cause-effect relationship between
smoking and sudden cardiac death has not been clearly documented, and the observations that hypothesize smoking as a risk
factor for sudden cardiac death are explained by statistical estimates
that analyse, indirectly, the phenomenon.
Epidemiologically, cerebrovascular disease ranks with the third
all-cause mortality and morbidity in civilized countries following
age and hypertension [69-70]. However, the relationship between
clinical patterns of cerebrovascular disease including stroke, recurrent stroke and transient ischaemic attack, and smoking is yet under
debate since existing opinions draw away from each to other. Generally, hypertension is the first factor which increases the risk of
both ischaemic and haemorrhagic stroke, while cigarette smoking
would act only in active smokers after lifetime exposure [71]. In
addition, there would be evidence that passive smoking is not
strongly associated with cerebrovascular disease. No association
between passive smoking and cerebrovascular disease including
stroke was found in five case-control, cross-sectional and cohortstudies [60, 72-75]. In contrast, the study of Bonita et al. [58]
showed a significant association between home passive smoking
and acute stroke in both male and female sexes. Moreover, there is
scientific evidence that Bonita et al. study is an excellent finding
that carefully analyses important variables related to cardiovascular
risk since it follows the diagnostic criteria of stroke defined by the
WHO [76]. Finally, it is worth noting that stroke of smokers is,
usually, an ischaemic rather than a haemorrhagic stroke because the
compounds of tobacco smoke primarily have a thrombotic mechanism, increasing platelet adhesiveness and aggregation.
Systemic artery disease shows, clinically, symptoms and characteristics of atherosclerosis progression [77] particularly at carotid
artery site. However, clinical symptoms depend on the arterial tree
compromised and, usually, are similar to those related to other factors, unless Burger disease (thromboangiitis obliterans) [78], where
claudication may be reduced by stopping smoking. In contrast, continuing smokers may develop gangrene followed by leg amputation
that concludes the spontaneous history of the disease. Observations
reported the appearance of Burger disease in never smokers and that
was probably due to passive smoking exposure [79-80].
smoked. In addition, past smokers have fibrinogen levels similar to

those of non-smokers.
Landini and Leone
There is an axiom of five words that undoubtedly underlines

how clinical claudication may be improved stop smoking and keep
walking [81].
Biochemical Variables
Cardiovascular alterations due to smoking depend on the effects
of some smoking compounds or, alternatively, they may be the results of changes in haematological parameters related to the degree
of atherosclerosis progression.
Among involved parameters (Table 3), some are related to
atherogenic and thrombogenic risk such as increased LDLcholesterol, low-density lipoproteins, triglycerides, total with, red,
and platelet blood cell count, hematocrit, prothrombine time, partial
thromboplastin time, and fibrinogen. Some others depend on pathological changes of myocardial cell components such as mitochondria, enzyme chains, intracellular bodies, and cellular receptors
[29].
Table 3. Biochemical Markers Involved in Cardiovascular
Damage from Smoking
Parameters Involved
Biological Variables
Thrombogenesis/thrombosis
Changes in platelet function

Changes in platelet shape
Coagulation-fibrinolysis changes
Arterial wall
Endothelial dysfunction
Arterial stiffness
Haematological parameters
Changes in blood cell count

Changes in blood cell shape
Increased C-reactive protein
Changes in blood viscosity
Metabolic parameters
Changes in lipid metabolism

Changes in glucose metabolism
Increased catecholamine release
Decreased estrogen levels
Oxidative stress
Immunological responses
Alterations in T-cell function

Reduced immune response
Susceptibility to infections
Platelet response and survival are adversely affected primarily

by chronic smoke although there is evidence that while a subject
smokes actively cigarettes, platelet adhesiveness and aggregation
increase acutely [82]. Endothelial dysfunction strongly influences
such a condition. Usually, normal endothelium is a non-reactive
structure with the constituents of circulating blood and it responds
to stimuli by a vasodilator mechanism primarily due to nitric oxide.
When endothelial surface is denudated or covered by prosthetic material, the coagulation-fibrinolysis cascade is activated by an elevated production of fibrinogen and thrombogenic factors including
factor VII, that contribute to non-occluding or occluding thrombi
formation. There is clear evidence that current smokers [83-85]
have higher fibrinogen levels related with the number of cigarettes
Endothelial dysfunction has been shown [19, 86-87] in both
healthy and ischaemic individuals.
Other haematolgical factors contribute to trigger atherosclerotic
process. Plasma viscosity interferes with red cell deformability,
while plasminogen, which contributes to the lysis of fresh thrombi,
reduces its concentration during exposure to cigarette smoke. Fibrinogen and factor VII are currently independent risk factors for
coronary artery disease and stroke [83, 88].
Tobacco smoke adversely influences several metabolic steps of
lipid and glucose metabolism with changes in concentration of
those substances actively involved in the protection or progression
of atherosclerotic process. Results showed that repeated measurements of blood lipid concentrations in both active and passive
smokers identified primarily LDL-Cholesterol and triglycerides increase and HDL-cholesterol decrease [89-92].
There are always newer data on the relationship between glucose metabolism and tobacco smoke. Smoking is an independent,
modifiable risk factor for non-insulin dependent diabetes mellitus
[93]. Findings on individuals exposed to active and passive smoking showed that smoking was associated with an increased risk of
developing glucose intolerance [94-98]. In addition, individuals
passively exposed to smoke had an intermediated risk of developing
glucose intolerance [98]. The degree of risk was similar to that of
past smokers after their quitting smoke.
Insulin resistance syndrome, which consists of a large number
of metabolic disorders affecting blood pressure, body weight,
changes in lipid and glucose metabolism and, primarily, high blood
insulin levels, is now recognized to be a risk factors for heart disease [99-100]. Findings [100-101] showed that smoking exposure
could increase insulin resistance particularly in women, although
another report did not support similar statement [102].
Cigarette smoking enhances the release of plasma catecholamine, inhibits cyclo-oxygenase- prostacyclin related, and increases
thromboxane byosynthesis [103]. Prostacyclin is a potent inhibitor
of platelet aggregation [104] while thromboxane is a potent vasoconstrictor and platelet agonist. Therefore, increased catecholamine
release acts either enhancing platelet aggregation or stimulating
sympathetic nervous system. Both these factors are able to induce
arterial lumen narrowing for a progression of atherosclerotic process via thrombus formation.
In this context, some considerations need oxidative stress. Cigarette smoking contains a large amount of oxidants and evidence
suggests that oxidative stress is involved in the pathogenesis of
many cardiovascular diseases [105-108]. Oxidative stress is the result of an imbalance between the production of reactive chemicals,
including reactive oxygen and nitrogen chemicals, with damaging
effects and biological systems deputed to readily detoxify the reactive intermediates in an attempt to easily repair the resulting damage. Reactive chemicals are, usually, smallest molecules with a significantly high reactivity. They play a strong role on cellular metabolism through specific modifications of cell signalling protein
[109] which leads to the activation of pathways that control cell
proliferation, hypertrophy, hypoxia and apoptosis [110]. By these
processes, antioxidant substances are inhibited and, then, cellular
damage progresses.
Finally, cigarette smoking may induce alterations in immune
function [111] influencing negatively T-cell activity and antibody
response. Inflammatory haematological markers can modify their
values in smokers with a major susceptibility to infections and
manifestations of increased plasma viscosity. Indeed, there is evidence that heavy smokers suffer frequently from chronic bronchitis
with recurrent exacerbation and altered immunological responses.
In addition, increased levels of C reactive-protein, documented in
heavy smokers, are an indicator of activated immune system and
inflammation, which, undoubtedly, favour atherosclerosis progression and occurrence of heart attacks.
Pathological Variables
Pathological alterations of heart and blood vessels caused by
cigarette smoking are similar qualitatively in both active and passive smokers, although active smokers, usually, absorb major concentrations of toxic compounds. In addition, structural alterations
caused by smoking are similar to those of other cardiovascular
events able to cause the same disease, unless for some ultrastructural manifestations, which seem to be typical lesions from
smoking. However, differences exist primarily for the site and size
of the alterations induced by smoking as well as for the choice of
some cardiovascular structures instead of others. Generally, at the
beginning of exposure, there is evidence that active smoking causes
mainly pathological alterations related to cardiac and cerebrovascular complications while passive smoking induces functional disorders [12, 31,112]. Table 4 lists the main manifestations of cardiovascular pathology due to both active and passive smoking according to their type and related incidence.
The major observations on the morphological alterations of cardiovascular system due to both active and passive smoking exposure [22, 29-31, 113] are coming from experimental findings conducted on animals exposed to smoking or carbon monoxide alone
[30, 52, 114-116]. The ultrastructural analysis of the damage identifies undoubtedly that carbon monoxide is the main factor of both
myocardium and artery lesions. The damage, however, may be a
consequence of either coronary circulation changes or a direct effect of carbon monoxide on cardiovascular system without any impairment in coronary circulation. In addition, nicotine supports hypoxic mechanisms of damage, which aggravates the effects of carbon monoxide at cellular level.
Myocardial necrosis and, particularly, its type-because there are
different patterns of necrosis- is the main pathological manifestation to be discussed. Necrosis may be well defined the result of
those morphological changes, which follow cell death in a living
tissue or organ with partial or total loss in their function. All infarcts of the myocardium belong to the group of necrotic lesions,
although not all cardiac necroses are necessarily infarcts. The necrosis of an infarct recognises a coronarogenic mechanism with
coronary vessel narrowing or occlusion, while some necroses, morphologically, affect directly myocardium with no coronary artery
involvement. Smoking exposure may cause the development of
both types of necrosis: necrosis supported by a coronarogenic
mechanisms and non-coronarogenic necrosis. Sometimes, both necroses may be associated with markedly morphological damage of
myocardial cells. Fig. (2) schematizes the main mechanisms which
support the different types of necrosis.
Microscopic alterations due to vascular mechanism follow steps
characterised by cellular lysis, fragmentation of cardiocytes and
disappearance of nuclei. Contract band formation, polimorphonuclear infiltrates and, then, formation of a granulation tissue, that will
evolve in a firm scar completing the healing process, usually accompany myocardial lesions . Coronary arteries usually show various degree of narrowing, partial or complete occlusion due to old
thrombi, superimposed fresh thrombi, atherosclerotic plaque rupture with, sometimes, distal embolisation. Coronary wall may contain calcium deposits. When non-coronarogenic mechanism causes
myocardial cell death, coronary alterations may be totally absent or
supported by minimal lumen narrowing.
A pathologic pattern specifically attributed to smoking action is
the smoke cardiomyopathy[114-115]. The term cardiomyopathy
is currently used to describe all those degenerative lesions of the
myocardium caused directly by toxic or metabolic substances and,
indirectly, by changes in oxygen availability with chronic hypoxia.
Therefore, smoke cardiomyopathy does not present typically
coronarogenic necrotic manifestations, but, instead, altered function
Landini and Leone
Table 4. Cardiovascular Pathology Related to Smoking Exposure

Cardiovascular Events
Active Smoking
Passive Smoking
+++
+++
+++
+++
++
Myocardial infarction
+++
+++
Arrhythmias
+++
++
Coronary artery disease

Stable angina
Vasospasm angina
Experimental cardiomyopathy
+++
Sudden cardiac death
+ (?)
+++
++
Stroke
+++
Recurrent stroke
+++
++
Transient ischaemic attack
+++
++
+++
++
+++
++
Cerebrovascular disease
Peripheral artery disease

Thromboangiitis obliterans
Symbols: +++ = elevated rate; ++ = moderate rate; ++ = mild rate; + (?) = uncertain rate.
Fig. (2). Main pathological mechanisms of myocardial necrosis. There is evidence that myocardial necrosis may be caused by a coronarogenic mechanism
involving coronary circulation as well as by a toxic mechanism without or with coronary circulation involvement.
and morphology of those intracellular components primarily in-volved

in carrying out metabolic and respiratory pathways. Experi-mental
studies [117-120] show that a wide number of factors can cause
alterations in myocardial cells. These alterations morphologi-cally
consist of myolysis, non-ischaemic necrosis, hyalinosis, and
inflammatory foci. Calcifications and fibrosis, particularly intersti-tial
fibrosis, often develop in the context of the lesions. Smoking
compounds, primarily carbon, monoxide induce, experimentally, all
these alterations associated with the presence of perivascular haemorrhagic infiltrates, which are specific manifestations of smoke cardiomyopathy [30]. Table 5 summarizes the main morpho-patho-logical
patterns of smoke cardiomyopathy.
Haemorrhagic foci into the

context of necrotic area need
some explanations since they
are a typical pattern of smoke
cardiomyopa-thy. Haemorrhagic
foci are necrotic zones of
myofilaments in the context of
which isolated or confluent
punctuate microhaemor-rhages
give a typical microscopic
aspect. These alterations are the
result of carbon monoxide
toxicity since they are strongly
associ-ated with gas poisoning
in a quantity much more extended than those of cigarette smoking. reduced up to a degree which
Carbon monoxide causes these altera-tions because of its link with strictly depends on blood
haemoglobin [121-124]. Oxygen availability to the myocardium is carboxyhaemoglobin
concentrations. In
Table 5. Morpho-pathological Patterns of Experimental Smoke

Cardiomyopathy
Pathological Feature
Myocytolysis
Main Characteristics
Colliquative degeneration of cardiocytes
Intracellular oedema
Nuclear alterations
Vacuolisation
Vascular damage
Perivascular infiltrates
Small artery wall inflammation
Hyalinosis
Homogeneous glassy deposits in myocardium

Homogeneous glassy deposits in arterial wall
Inflammation
Inflammatory cell infiltrates

Cardiocyte necrosis
Haemorrhagic foci
Fig. (3). Smoke cardiomyopathy: microhaemorrhagic interstitial infiltrates

(white line) and severe alterations in myocardial fibers. Isolated and confluent areas of interstitial fibrosis may be seen.
Perivascular and interstitial foci

Punctate haemorrhage into myocardium
Fibrosis
Perivascular fibrosis
Interstitial fibrosis
Calcium deposit
Arterial wall and myocardium

Atheroma of advanced atherosclerosis
addition, myocardial infarction in individuals with normal coronary

arteries may be caused by this mechanism as an interesting paper
shows [124].
Figures (3) and (4) show same ultrastructural patterns of experimental smoke cardiomyopathy.
The analysis of these observations shows that severe morphopatholgical changes in coronary circulation and myocardial cells
may be seen, either when they are isolated or differently combined
among themselves. That may cause a large spectrum of pathological features, which lead to impairment or aggravate both preexisting myocardial function and structure.
Fig. (4). Smoke cardiomyopathy. Presence of contract bands as a result of

coagulative necrosis.
The pathologic changes in cerebrovascular circulation are similar of coronary circulation even if they are primarily related to active smoking. Smoking damages cerebral circulation by two main
mechanisms often associated (Table 6). They cause morphopatological alterations of ischaemic or haemorrhagic type. Usually
ischaemic lesions occur with higher rate since they are well related
to atherosclerosis progression or thrombosis, while haemorrhagic
alterations are a consequence of artery wall rupture mainly due to
severe o malignant hypertension in elderly.
Cerebral arteries usually show narrowing of different degree
with, sometimes, intimal rupture and non-occlusive or occlusive
superimposed thrombi. Figs. (5) and (6) are an example of two
types of morphopathological alterations of cerebral arteries.
Findings demonstrate that thickness in carotid artery wall
deeply influences the morphology of cerebrovascular circulation.
Indeed, smoking is a strong risk factor for carotid wall thickening
[59, 75].
The effect of smoking on arterial stiffness needs some observations since changes in artery distensibility adversely influence both
haemodynamic and structural responses of cardiovascular function.
Fig. (5). Anterior cerebral artery with mild intimal thickness and moderate
lipid subintimal circular deposits (our autopsy observation).
Stefanidis et al. [125] investigated aortic elasticity in male patients

Fig. (6). Anterior cerebral artery. There is evidence of narrowing caused by

an eccentric thrombus, which is partly calcified, and fragmentation of elastic
fibers (our autopsy observation).
Table 6. Morphopathological Alterations of Cerebrovascular

Disease Caused by Smoking Exposure.
Mechanism
Atherosclerosis
Morphopathology
Cerebral artery narrowing
Cerebral Disease
Transient ischaemic attack
Ischaemic stroke
Recurrent ischaemic
stroke
Cerebral atrophy
Thrombosis
Cerebral artery occlusion
Ischaemic stroke
Recurrent ischaemic
stroke
Haemorrhage
Wall artery rupture
Haemorrhagic stroke
Impairment or loss in arterial elasticity actively induce atherosclerotic lesions similarly to other damaging mechanisms related to
smoking.
Morphopathological alterations in systemic arteries are, usually,
those of atherosclerotic lesion, unless thromboangiitis obliterans
[78] where inflammatory elements are prevailing. Indeed, thromboangiitis obliterans is an arteriopathy from cigarette smoking.
In conclusion, there is no doubt that both active and passive
smoking cause severe clinical, biochemical and pathological alterations of cardiovascular system. These alterations are the result of
the combined harmful effects of tobacco smoke compounds, primarily nicotine and carbon monoxide. However, the latter undoubtedly has a greater role in inducing morphopathological lesions by a
double mechanism of action: a direct effect on myocardium and
arterial wall because of its toxicity, and an effect mediated by carboxyhaemoglobin with reduced oxygen availability. Therefore, ex-
most of whom had coronary ischaemic disease. Exposure to passive

smoking significantly reduced aortic distensibility with increased
left ventricular afterload and worsening in myocardial function.
posure to smoking is a strong risk for both healthy and individuals
with pre-existing cardiovascular disease. American Heart Associa-
Landini and Leone
tion, as the excellent paper of Glantz and Parmley emphasizes [14],

included also passive smoking among the major risk factors for
heart disease in both adults and children. In addition, evidence indicates that a strong relationship links smoking with arterial
hyperten-sion.
HYPERTENSION AND CARDIOVASCULAR SYSTEM
Hypertension is one of the major modifiable risk factors for
coronary, cerebrovascular and other vascular diseases since numerous drugs are able to reduce both systolic and diastolic blood pressure values. However, despite large-scale approaches to diagnose,
treat and educate lifestyle of hypertensive patients, the impact of
hypertension control is strongly discouraging [126] either for the
scarce attention of the patients with regard to their blood pressure
or for poor results related to treatment. In addition, there is
evidence that the early stages of hypertension are asymptomatic,
and such a fact contributes, usually, to identify hypertensive
patients for an occasional clinical control or for dated vascular
complications. Therefore, clinical and pathological variables of
hypertensive dis-ease are mainly related to the cardiovascular
complications, despite the fact that some data on an existing
hypertension could be de-duced by measurements of some
biochemical parameters, which are, however, many expensive and,
then, not fully estimated by large-scale methods. However,
hypertensive patients need a careful control particularly after a
diagnosis of hypertension in an attempt to assess whether they meet
lowering in blood pressure during ther-apy or, on the contrary,
appearance of target organ damage.
Clinical Variables
Initial clinical symptoms of hypertension are of difficult assessment either for the different lifestyle of groups of population or
for the characteristics of elevated blood pressure [127-132]. On the
contrary, the symptoms related to complications of hypertension
may be easily identified and, therefore, talking of hypertensive vascular disease would be more correct.
Three types of symptoms, usually, carry hypertensive patients
to the physician (Table 7): symptoms related to elevated blood
pressure, symptoms associated with target organ damage and symptoms of an underlying disease in presence of secondary hypertension. However, the large majority of individuals with early hypertension have no clinical symptoms and signs or, at a maximum, a
merely cardiac enlargement when compensated hypertension exists.
Table 7. Symptoms and Signs of Hypertensive Patients.
Symptom Categories
Clinical Signs
1. Symptoms related to high blood pressure
Morning headache
Dizziness
Walking fatigue
Others (aspecific)
2. Symptoms associated to target organ damage
Epistaxis
Hematuria
Blurring vision
Chest pain
Dyspnoea
3. Symptoms related to underlying disease
Those of underlying
disease
Other signs that can help to assess hypertension are a family

history of elevated blood pressure or vascular disease and appearance of newer symptoms related to ischaemic heart disease, heart
failure, cerebrovascular troubles and peripheral vascular insufficiency.
These data put in evidence that it is necessary addressing the
attention on the heart, neurological system and kidney in an attempt
to deduce retrospectively whether a patient had been affected by
early hypertension. On the contrary, long-standing hypertension
records rapidly symptoms of target organ involvement. A clinical
syndrome which requires a careful control is hypertensive encephalopathy [133-135]. Hypertensive encephalopathy is a neurological
dysfunction induced by malignant hypertension. It is a cerebral
condition, typically reversible, caused by sudden and sustained
severe elevation of blood pressure. It occurs in eclampsia, acute
nephritis and hypertensive crises. Clinical symptoms consist of a
complex of alterations characterized by severe hypertension, altered
consciousness, increased intracranial pressure with sickness and
vomiting, retinopathy with papilledema, and seizures. The pathogenesis of hypertensive encephalopathy is yet under discussion and
doubts have been hypothesized on a possible vascular mechanism.
The syndrome may be accompanied to focal or massive haemorrhagic cerebral infarct, and there is no common opinion that it could
be controlled by a rapid lowering of blood pressure.
Baseline electrocardiography and echocardiography constitute a
valid support to assess clinical manifestations of hypertension.
The described signs may lead to a diagnosis of hypertension,
which, however, may be easily documented whether the physicians
control routinely blood pressure in their patients every time during a
medical exam.
Biochemical Variables
Biochemical variables which may provide details on the
mechanisms and prognostic significance of hypertension belong to
two main categories: biochemical evaluation of routine blood samples and specific biochemical substances related to pathogenetic
mechanisms of hypertension.
Together with clinical exam, assessing biochemical variables is
a useful support in an attempt to establish those markers of known
causes of hypertension, to stratify hypertensive individuals with
regard to their age, sex and race, and, then, to define the true risk
profile of an individual towards hypertension. In addition, novel
markers associated with hypertensive heart disease and heart failure
from hypertension should be monitored [136-138]. Table 8 summarizes the main biochemical markers to assess for a correct interpretation of different types of hypertension.
These markers allow a more correct approach to interpret, treat
and identify the type of hypertension.
Among the biochemical markers related to routine control,

complete blood count with hematocrit, glucose and lipid profile are
also involved in the damage caused by cigarette smoking [82-84,
88-102]. On the contrary, other markers are specific for assessing
the role of elevated blood pressure. Plasma renin primarily feels
changes in sodium balance [139-141]. Plasma renin activity may
screen high blood pressure of kidney origin as well as allow planning the treatment of essential hypertension often aggravated by
excess sodium intake. In addition, plasma renin activity helps to
evaluate the diagnosis of excess aldosterone.
Enhanced plasma renin activity probably contributes to early
phase of hypertension, although there would be evidence that it
mainly related to the development of severe hypertension. Controversies, however, exist on this hypothesis.
The measures of renin-sodium profile associated with the assessment of plasma potassium, serum urea and creatinine, 4-hr
Table 8. Biochemical Markers in Hypertension.

Variables
1. Variables related to routine control
Biochemical Markers
Complete blood count with hematocrit
Urine analysis
Blood urea nitrogen
Serum creatinine
Serum uric acid
Fasting blood sugar
Lipid profile
Serum electrolytes
2. Variables related to specific patterns
Plasma renin
Plasma and urinary catecholamine
Urinary free cortisol
Urinary 17hydroxycorticosteroids
Urinary aldosterone
2996
Current Pharmaceutical Design, 2011, Vol. 17, No. 28
with left ventricular hypertrophy but not heart failure [149-151].

Therefore, there would be evidence that CT-1 may be a biochemical
marker, which allows following the progression of hypertensive
disease and the involvement of cardiac muscle.
Annexin A5 is a protein involved in cardiomyocyte apoptosis
[152-153]. Its increase in concentration occurs experimentally or
clinically in either hypertensive animals or patients developing left
ventricular hypertrophy and, particularly, heart failure. Available
data suggest that plasma Annexin A5 in hypertensive patients would
be an effective biochemical marker of apoptosis-related cardiomyocyte dysfunction and, by this way, it may contribute to interpret both hypertension course and target organ involvement including specifically heart involvement.
Finally, collecting data demonstrate that biochemical markers of
hypertension are continuously in progress and, moreover, novel
markers would be related to manifestations of cardiovascular damage which is very similar to that due to smoking exposure.
Pathological Variables
Pathological variables of hypertension include a great number
of morphological alterations which are well dated and known. This
statement is true in its context when hypertensive vascular disease
is analysed namely and the complications of hypertension display
target organ damage. Indeed, early hypertension, usually clinically
and metabolically asymptomatic, does not show pathological alterations of high degree.
Pathological alterations of early hypertension consist, the most,
of a moderate cardiac enlargement with mild or no hypertrophy and
a few changes of arteriosclerotic type in small arteries due to vasoconstriction of peripheral circulation. These alterations would be a
consequence of increased afterload caused by elevated blood pressure or, probably, they pre-exist to hypertension according to the
results of some studies [154]. Isolated areas of fibrosis also may be
seen in several organs like heart and kidney with, however, no
change in shape and gross morphology of them.
3. Novel biochemical substances
Plasma CT-1
Annexin A5
microalbuminuria excretion rate and 24-hr urinary sodium and potassium values are useful biochemical markers to identify either
secondary causes of hypertension or the pathophysiologic profile of
the patients. In addition, they may be predictors of vascular disease
or benign essential hypertension [142-143].
Biochemical markers of lipid and glucose profile address to the
same considerations described for the action of smoking compounds. These markers may be elevated in several forms of secondary hypertension, like Cushings syndrome and pheochromocytoma that are associated with hyperglycaemia and changes in hormone release respectively corticosteroids and catecholamine [144145]. A reduction in lipid concentration can be a factor improving
blood pressure, even if doubts have been raised more recently [146147]. It would seem that biochemical variables of hypertension and
smoking are walking on two parallel ways with a meeting point
when the damage caused by each of them reaches its maximum degree.
The markers specifically related to structural components of the
heart are pathological substances, which provide important data on
the outcome of both hypertensive disease and target organ damage.
Among these markers, Cardiotrophin-1 (CT-1), belonging to interleukin-6 family, and Annexin A5 have been, primarily, measured in
hypertensive patients. These biochemical compounds exert their
action on the same tissues, like heart muscle, also target organ of
smoking compounds.
CT-1 is produced by cardiocytes and cardiac fibroblasts in case
of functional or mechanical stress [148]. Increased concentration of
CT-1 has been documented in hypertensive patients particularly
with left ventricular hypertrophy as well as in those patients developing heart failure with a higher concentration than that of subjects
A wide spectrum of pathological alterations characterizes complicated hypertension to the macroscopic or histological exam.
Some cases, undergone autopsy in our observations, showed a different degree of target organ damage as Figs. (7-10) and (11) clearly
show. The subjects died for a cardiac event complicating the
hypertension. However, vascular alterations affecting the arteries of
the other target organs are quite similar to coronary alterations, unless for the brain where rupture of the wall of cerebral arteries
associated with haemorrhagic stroke may be seen.
Landini and Leone
by the technique of Roussy and Ameuille [158]. By this method, the heart is
cut in transverse slices of thickness approximately 1 cm, parallel to each
other. Myocardial alterations may be recorded and, then, measured by the
analysis of the photograph.
Fig. (8). Post-mortem study of the heart in a patient with essential hypertension. A moderate cardiac hypertrophy may be seen. The heart was examined
Fig. (9). Minimal changes in the arterial wall due to hypertension.
Fig. (7). Rupture of the heart

following an acute myocardial
infarct in a pa-tient with severe
hypertension. There is evidence of
rupture of the free wall of the left
ventricle into the area of infarct and
severe hypertrophy of the heart.
Hypertensive
subjects
with
myocardial infarct and cardiac
hypertro-phy undergo frequently
postinfarction cardiac rupture [155157].
Fig. (10). Changes in arterial wall

due to hypertension. There is
moderate narrowing and increased
thickness of the arterial wall with
patent arterial lumen.
Pathological alterations of hypertension complicated by target

organ damage are, however, not strictly specific of the disease.
Pathological diagnosis of hypertensive heart disease with cardiac
hypertrophy, left ventricular thickening and increase in size and
weight of the heart can be made only when other cardiac abnormalities able to cause similar alterations like valvular lesions, some
congenital heart disease and diseases of the aorta can be absolutely
excluded. Indeed, the autopsy technique for heart exam proposed by
Roussy and Ameuille [158] well helps to make a differential diagnosis.
Cardiac hypertrophy due to hypertension is defined a concentric
hypertrophy since it occurs, once the early stage of hypertension
has passed, at expense of the left ventricular chamber which reduces significantly its volumetric width. When hypertension is
complicated by heart failure, an important cardiac enlargement occurs with reduced thickening of left ventricular wall and pump
function.
In conclusion, pathological variables observed in hypertensive
individuals at the autopsy are similar to those triggered by cigarette
smoking inducing atherosclerotic plaque progression. The chemicals released by smoking strongly support vascular alterations of
complicated hypertension.
Fig. (11). An almost total occlusive (95%) thrombus in a coronary artery of

a subject with severe hypertension.
Two main mechanisms play a basic role to cause pathological

alterations of cardiovascular system in patients with vascular hypertensive disease: increased afterload and increase of peripheral arterial resistance, which is a consequence of vasoconstriction caused
by mechanical but also biochemical variables of the hypertension.
COMBINED SMOKING AND HYPERTENSION

The effects of the combined action of smoking and hypertension on the cardiovascular system usually involve several vascular
beds, which, in its turn, may determine functionally abnormal responses as well as specifically clinical symptoms. Coronary, cerebral and carotid arteries are, primarily, adversely affected.
The relationship between cigarette smoking and left ventricular

mass was investigated by Verdecchia et al [159]. In this casecontrol study, the association of blood pressure with heavy cigarette
smoking (equal or more than 20 cigarettes/day) adversely influenced left ventricular mass in male and female essential hypertensive patients.
Coagulation-fibrinolysis system is another parameter involved
in cardiovascular damage caused by smoking and associated hypertension.. Smoking adversely influences coagulation-fibrinolysis
cascade with alterations of the thrombogenic mechanisms [160-
161]. Similarly, hypertension feels the adverse effects related to

changes in plasma viscosity and hematocrit [84, 133].
Atherosclerosis in smokers develops approximately 10 years
earlier than that in non-smokers [162]. Indeed, a very high percentage (84%) of smokers was in a group of inpatients with unilateral or
bilateral renal artery stenosis [163], an occurrence which is able to
cause hypertension with high rate.
The association of hypertension with cigarette smoking is frequent in patients with malignant hypertension [164-165]. In particular, there was evidence that hypertensive smokers are 5 times more
likely to develop malignant hypertension than non-smokers are
[166].
Although cigarette smoking may not be associated with the development of essential hypertension, its significant impact on prognosis of hypertensive patients has been extensively documented by
several epidemiological and prospective trials. In the Multiple Risk
Factor Intervention Trial (MRFIT), the age-adjusted rate of coronary artery disease death was greater in smokers than that nonsmokers at all levels of blood pressure [167]. Data from the Systolic
Hypertension in the Elderly Program (SHEP), a clinical trial that
evaluated the benefit of treating over 60-year-old patients with isolated systolic hypertension ( 160 mmHg), indicated that cigarette
smoking independently increased the risk of cardiovascular disease
events by more than 50% [168]. The more recent Hypertension Optimal Treatment (HOT) trial [169] analysed cardiovascular morbidity and mortality of over 18,000 hypertensive patients subjected to
intensive lowering of diastolic blood pressure. These data have subsequently been analyzed after stratification of the patients according
to global cardiovascular risk, and, even after effective lowering of
elevated diastolic blood pressure, other cardiovascular risk factors
still played an important role in determining the residual risk of hypertensive patients [170]. In particular, it was clearly demonstrated
that the highest total mortality was seen in smokers with an incidence of approximately twice as high as in non-smokers. The harmful effect of smoking was evidenced even during a short observational period.
Large-scale trials conducted in hypertensive patients show undoubtedly that hypertension is a strong risk factor which aggravates
the harmful atherosclerotic effects of smoking on cardiovascular
system although there is evidence that smoking, usually, precedes
the appearance of hypertension. Building the stairs of cardiovascular damage, smoking is at the first step followed by hypertension.
Therefore, there is a close relationship between these two factors
that, possibly, act independently but also additively on vascular
damage.
Clinical trials have shown that lowering blood pressure below
140 mmHg for systolic and 90 mmHg for diastolic values determines both clinical and prognostic benefits. Moreover, blood pressures between 120/80 and 139/ 89 mmHg have identified a pattern
defined pre-hypertension which may be considered a precursor of
stage 1 hypertension and predictor of excessive cardiovascular risk
Acute exposure to passive smoking adversely influences either
blood vessel dilation, since there is a reduced release of NO, or arterial stiffness with increased blood pressure values. Although the
type of pathological changes accompanying blood pressure is, usually, proven later, there is evidence that it begins acutely while an
individual smokes [14].
Therefore, smoking and hypertension, when they act together,

are two parallel tracks directed towards the same station: the station
of an increase of cardiovascular damage.
In conclusion, even if assessing the course of systolic blood

pressure immediately after smoking exposure may be difficult unless in experimental findings, one cannot deny its increase related to
smoking exposure. Thus, adverse effects of smoking on the arterial
wall are pre-existing to the hypertension, which, usually, could appear when structurally severe and irreversible alterations begin
[172].
CONFLICT OF INTEREST
No.
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Current Pharmaceutical Design, 2011, 17, 2987-3001

Smoking and Hypertension: Effects on Clinical, Biochemical and Pathological

Keywords: Smoking, hypertension, combined action, cardiovascular system.

them as old as fewer 70 years.

Worldwide, more than 3

2988 Current Pharmaceutical Design, 2011, Vol. 17, No. 28

Table 1. Tobacco Chemicals Damaging Cardiovascular System

Sympathetic system, Vascular bed,

Arterial wall, Myocardium

Thyroid metabolism, Blood vessels

Arterial wall, Myocardium

Arterial wall, Myocardium

Nicotine [41-42] is an alkaloid that constitutes approximately

Landini and Leone

lated to carbon monoxide inhaled smoking cigarettes or that

Smoking and Hypertension

Current Pharmaceutical Design, 2011, Vol. 17, No. 28 2989

Table 2. Main Clinical

Clinical damage is often associated with other types of damage

Coronary heart disease associated with clinical symptoms may be

significant increase in carboxyhaemoglobin not associated with

Smoking and Hypertension

smoked. In addition, past smokers have fibrinogen levels similar to

Landini and Leone

There is an axiom of five words that undoubtedly underlines

Changes in platelet function

Changes in blood cell count

Changes in lipid metabolism

Alterations in T-cell function

Platelet response and survival are adversely affected primarily

Current Pharmaceutical Design, 2011, Vol. 17, No. 28 2991

2992 Current Pharmaceutical Design, 2011, Vol. 17, No. 28

Landini and Leone

Table 4. Cardiovascular Pathology Related to Smoking Exposure

Coronary artery disease

Sudden cardiac death

Transient ischaemic attack

Peripheral artery disease

and morphology of those intracellular components primarily in-volved

Haemorrhagic foci into the

Current Pharmaceutical Design, 2011, Vol. 17, No. 28 2993

Table 5. Morpho-pathological Patterns of Experimental Smoke

Homogeneous glassy deposits in myocardium

Inflammatory cell infiltrates

Fig. (3). Smoke cardiomyopathy: microhaemorrhagic interstitial infiltrates

Perivascular and interstitial foci

Arterial wall and myocardium

addition, myocardial infarction in individuals with normal coronary

Fig. (4). Smoke cardiomyopathy. Presence of contract bands as a result of

Stefanidis et al. [125] investigated aortic elasticity in male patients

Fig. (6). Anterior cerebral artery. There is evidence of narrowing caused by

Table 6. Morphopathological Alterations of Cerebrovascular

Cerebral artery occlusion

Wall artery rupture

most of whom had coronary ischaemic disease. Exposure to passive

Landini and Leone

tion, as the excellent paper of Glantz and Parmley emphasizes [14],

1. Symptoms related to high blood pressure

2. Symptoms associated to target organ damage

3. Symptoms related to underlying disease

Smoking and Hypertension

Other signs that can help to assess hypertension are a family

Among the biochemical markers related to routine control,