Multiple Sclerosis and Related Disorders (2013) 2, 355361

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/msard

Prevalence and incidence of ischemic heart

disease in multiple sclerosis: A
population-based validation study
Ruth Ann Marrie, Bo N. Yu, Stella Leung, Lawrence Elliott,
Patricia Caetano, Sharon Warren, Christina Wolfson, Scott B.
Patten, Lawrence W. Svenson, Helen Tremlett, John Fisk,
James F. Blanchard

University of Manitoba, Health Sciences Centre, GF 533, 820 Sherbrook Street, Winnipeg, MB, Canada R3A
1R9

Received 21 December 2012; received in revised form 16 February 2013; accepted 7 March 2013

KEYWORDS Abstract
Multiple sclerosis; Background: Studies suggest an altered risk of ischemic heart disease (IHD) in multiple
Cardiac disease; sclerosis (MS), but data are limited. We aimed to validate and apply administrative case
Administrative data; denitions to estimate the incidence and prevalence of IHD in MS.
Validation; Methods: Using administrative data we identied persons with incident MS (MSPOP) and
Prevalence;
a matched general population (GPOP) cohort. We developed case denitions for IHD using
Incidence
ICD-9/10 codes and prescription claims, compared them to medical records, then applied them
to evaluate the incidence and prevalence of IHD.
Results: Agreement between medical records and the administrative denition using 1
hospital or 2 physician claims over 5 years was moderate (kappa= 0.66; 95% CI: 0.420.90).
In 2005, the age-standardized prevalence of IHD was 6.77% (95% CI: 5.488.07%) in the MSPOP
and 6.11% (95% CI: 5.566.66%) in the GPOP. The prevalence of IHD was higher in the MSPOP
than the GPOP among persons aged 2044 years (prevalence ratio 1.87; 95% CI: 1.652.12) and
aged 4559 years (prevalence ratio 1.21; 95% CI: 1.081.35). The incidence of IHD was also
higher in the MSPOP (incidence rate ratio 1.24; 95% CI: 0.971.59).
Conclusions: More than 5% of the MSPOP has IHD. The incidence of IHD was higher than
expected in persons aged o60 years. Further evaluation of this issue is warranted.
& 2013 Elsevier B.V. All rights reserved.

1. Introduction

In immune-mediated conditions such as rheumatoid arthritis

Corresponding author. Tel.: +1 204 787 4951; fax: 1 204 787 1486. and psoriasis, the risk of ischemic heart disease (IHD) is
E-mail address: rmarrie@hsc.mb.ca (R.A. Marrie). increased (Crowson et al., 2005; Gelfand et al., 2006). Several

2211-0348/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.msard.2013.03.001
356
studies suggest that diabetes, hypertension and hyperlipidemia
are common in multiple sclerosis (MS) (Marrie et al., 2008,
2012a,b). While these conditions are associated with an
increased risk of IHD, ndings regarding the risk of IHD in MS
are conicting (Fleming and Blake, 1994; Redelings et al., 2006;
Allen et al., 2008); (Koch-Henriksen et al., 1998). The issue of
comorbid IHD is an important one in MS because it increases the
risk of premature death, and is associated with increased risks
of cerebrovascular and peripheral vascular disease (Alberts
et al., 2009; Mehlsen et al., 2010). Further, IHD is associated
with increased disability progression in MS (Marrie et al., 2010).
Finally, new disease-modifying medications are emerging where
the presence of comorbid cardiac disease may inuence the
safety of using those therapies (Cohen, 2009; European
Medicines Agency, 2012). Thus it is important that the risk of
IHD in MS be better characterized; and this can only be done if
methods for the ascertainment of IHD amongst individuals with
MS are developed and validated.
We aimed to develop and validate a case denition for
ischemic heart disease using administrative data; and to
apply this denition to estimate the incidence and pre-
valence of IHD in persons with MS and a matched cohort
from the general population. Unlike prior studies we did not
limit our study to hospitalized persons, to comprehensively
assess the incidence and prevalence of IHD.
2. Materials and methods
2.1. Study setting
This was a population-based analysis of administrative (health
claims) data for the period 19842005, conducted in Manitoba,
a Canadian province with a population of approximately 1.2
million (Health Information Management Branch, 2008).
2.2. Administrative data
Manitoba Health, a provincial government department, pro-
vides health care services to 98% of the population (Health
Information Management Branch, 2008). Since 1984 all hospital,
physician and prescription claims submitted to Manitoba Health
include a personal health identication number (PHIN) which
uniquely identies the person receiving the service. Each
hospitalization record includes admission and discharge dates,
and up to 16 discharge diagnoses listed using International
Classication of Disease (ICD)-10-CA codes. Before 2004, dis-
charge diagnoses were recorded using ve-digit ICD-9-CM codes.
Physician claims include the date of service, and three-digit
ICD-9-CM code for one physician-assigned diagnosis for all
physicians irrespective of physician type (e.g. primary care
provider versus specialist). Since 1996 the Drug Programs
Information Network captures the date, drug name and
identication number for all outpatient prescription drugs
which are dispensed to Manitoba residents.
2.3. Study populations
Previously, we validated an administrative case denition
for MS (Marrie et al., 2010) which we applied to identify all
persons with MS in Manitoba. We used the date of the rst
R.A. Marrie et al.
claim for demyelinating disease (e.g. transverse myelitis) as
the date of MS diagnosis. To ensure that we were using
incident cases of MS we required a ve-year lookback period
with no demyelinating disease claims. Since our data were
available from 1984 onward this meant that the rst MS case
could be identied in 1989. After excluding persons with any
diagnostic codes for demyelinating disease, we identied a
cohort from the general population, matched on sex, year of
birth and region of residence (postal code) to the MS cohort,
with up to 5 controls for each case. Controls were assigned
the same index date as their matched controls. A population
registry is maintained by Manitoba Health, and it is updated
when an individual moves into or out of Manitoba, changes
marital status, or dies. Thus persons with MS or their
matched controls were included in the analysis from the
index date until the end of the study (2005), death or
emigration from Manitoba, whichever came rst.
2.4. Validation cohort
As detailed elsewhere, our validation cohort included 430
persons with denite MS (Marrie et al., 2010) drawn from two
studies (Horton et al., 2010; Marrie et al., 2010). In both
studies, participants consented to review of their medical
records, and to linkage of their administrative and clinical
data. A blinded, trained, abstractor used a standardized data
collection form to capture comorbidities from the medical
records of all participants (Marrie et al., 2010). Participants
also completed a questionnaire regarding their comorbid-
ities, including heart disease (Horton et al., 2010).
2.5. Case denitions for IHD
After a literature review, we selected ICD-9/10 codes for IHD
(410414, I20I25) (Austin et al., 2002; Rector et al., 2004; Lix
et al., 2008; Varas-Lorenzo et al., 2008). We generated lists
of prescription medications available for treatment of IHD in
Canada using the Anatomic Therapeutic Chemical system,
including C01 (cardiac therapy), C07 (beta-blockers), C08
(calcium channel blockers), and C09 (agents acting on renin-
angiotensin system) (Lix et al., 2008). Finally, we developed
candidate case denitions, varying the number of physician,
hospital and prescription claims required and the number of
years used to classify a person as having IHD.
Using the validation cohort, we compared the classication
of IHD cases using administrative denitions with cases
dened by medical records review, using sensitivity, speci-
city, positive predictive value and negative predictive value.
Youden's J, an index that equally weights sensitivity and
specicity, was calculated as: (sensitivity+specicity) 1
(Youden, 1950). We also report a kappa () statistic for the
agreement between administrative and medical records data,
interpreting as follows: slight (00.20), fair (0.210.40),
moderate (0.410.60), substantial (0.610.80), and almost
perfect agreement (0.811.0) (Landis and Koch, 1977).
2.6. Prevalence and incidence
We applied selected case denitions to both study popula-
tions. Once a person met the case denition for IHD, he or she
was dened as affected in all subsequent years while alive and
Prevalence and incidence of ischemic heart disease in multiple sclerosis
resident in Manitoba (National Diabetes Surveillance System,
2003). The point prevalence was estimated on October 1 each
year using the mid-year population gures from the Manitoba
Health registry for denominators in the calculations. To
estimate incidence we required a 5-year run-in period pre-
ceding the rst IHD claim to ensure that cases were truly
incident. We estimated age and sex-specic incidence and
prevalence using age groups 2044, 4559, and 60 years and
older, which were selected to ensure adequate cell sizes to
protect participant condentiality.
We age-standardized the incidence and prevalence results
to the 2001 Canadian population (Rothman and Greenland,
1998) and 95% condence intervals (CI) were calculated using
an exact binomial distribution. In a matched cohort design a
matched analysis is not needed (Rothman and Greenland,
1998) and adjustment is not needed to control for confound-
ing due to the matched variables if follow-up time is the
same in both cohorts. If follow-up time is not the same due to
differential survival for example, then adjustment is needed.
Because of overdispersion we used negative binomial regres-
sion to calculate prevalence ratios (PR) and incidence rate
ratios (IRR) and 95% CI between the MS and control groups,
adjusting for sex, age, and scal year.
The University of Manitoba Health Research Ethics
Board approved the study and the Manitoba Health Informa-
tion Privacy Committee approved administrative data
access. To protect condentiality data linkage was per-
formed via scrambled PHIN, using anonymized versions of
the administrative databases. Informed consent was
obtained from participants in the validation cohort. Statis-
tical analyses were conducted using SAS 9.2 (SAS Institute
Inc., Cary NC).
3. Results
3.1. Participants
The study population included 2366 persons with incident
MS (74% female) and 11,786 persons from the general
population (Table 1). The validation cohort comprised
430 persons with MS, most of whom were white (391,
91.6%), women (331, 77.0%), with a mean (SD) age at
symptom onset of 33.2 (11.1) years, similar to other MS
populations (Jacobs et al., 1999). Of these 422 had com-
plete data regarding heart disease. The frequency of heart
Table 1 Characteristics of the study populations from 1989 to 2005.
Characteristic
n 2366
Female, n (%)
Age at rst demyelinating disease claim (years)a, mean (SD)
Person-years of observation
No. incident IHD cases
Censored due to death or migration, n (%)
Alive and disease free at end of study period, n (%)
a
Index date for matched controls from general population.
357
disease based on medical records review was 2.8% (n= 12),
and was 5.7% (n= 24) based on self-report.
3.2. Case denitions
We tested several administrative case denitions (labeled
AP) for IHD (Table S1). Agreement between case denitions
and medical records ranged from 0.48 (moderate) to 0.73
(substantial). Agreement was highest for case denitions C
(1 physician and 2 prescription claims in one year;
k = 0.72) and D (2 physician and 1 prescription claims
in one year; k = 0.73). Both of these denitions produced
high specicities of 99.5100%, but modest sensitivity (58.3
66.7%).
3.3. Prevalence
Denition D had the highest value (0.73) when compared
with medical records review. Denition N had a slightly
lower value of (0.66) but similar sensitivity and specicity.
Using denition N, the crude prevalence of IHD in 2005
was 5.90% (95% CI: 4.947.05%) in the MS population and
5.17% (95% CI: 4.7615.63%) in the controls. The age-
standardized prevalence was 6.77% (95% CI: 5.488.07%) in
the MS population and 6.11% (95% CI: 5.566.66%) in the
controls. Since this denition produced a prevalence of IHD
in the general population consistent with the published
literature (Chow et al., 2005) and could be used even in
jurisdictions without prescription claims, subsequent ana-
lyses used this denition.
The prevalence of IHD increased with age (Table 2) in
both populations. When stratied by age group (p for
interaction [age group population] = 0.0008), a negative
binomial model adjusting for sex and scal year showed that
the prevalence of IHD was higher for persons with MS than in
the controls for persons aged 2044 years (PR 1.87; 95% CI:
1.652.12), and persons aged 4559 years (PR 1.21; 95% CI:
1.081.35). In persons aged 60 years, however, the pre-
valence of IHD was lower in the MS population than the
controls (PR 0.81; 95% CI: 0.700.92).
Women in both populations and across all age groups had
a lower prevalence of IHD than men, although the disparity
between sexes decreased with increasing age. Thus, after
adjusting for year and population (MS versus controls), in
persons aged 2044 years, women had a 68% lower
Multiple sclerosis population General population
11786
74.1 74.1
40.5 (12.4) 40.5 (12.4)
16848.43 83604.64
82 330
272 (11.5) 1237 (10.5)
2012 (85.0) 10219 (86.7)
358 R.A. Marrie et al.

Table 2 Prevalence per 100,000 persons of ischemic heart disease in 2005 in the multiple sclerosis and general populations,
according to age and sex.

Age (years) Multiple sclerosis General population

Females Males Females Males

Prevalence 95% CI Prevalence 95% CI Prevalence 95% CI Prevalence 95% CI

2044 0.44 0.14, 1.35 2.29 0.86, 6.09 0.26 0.14, 0.50 0.82 0.39, 1.72
4559 3.23 2.10, 4.95 12.5 8.81, 17.8 3.17 2.62, 3.83 7.08 5.74, 8.73
60 17.2 12.2, 24.2 29.5 20.6, 42.2 17.7 15.3, 20.5 28.1 24.0, 32.9
Total 3.70 2.85, 4.79 12.3 9.69, 15.7 3.77 3.36, 4.22 9.36 8.26, 10.6

Table 3 Average annual incidence per 100,000 person years of ischemic heart disease (IHD) in the MS population and
matched general population cohort by gender and age group in Manitoba, 19892005.

Age Females Males F:M Both

(years)
No. No. Rate No.
Rate 95% CI Rate 95% CI 95% CI Rate 95% CI
IHD IHD ratio IHD

Multiple sclerosis

2044 a 81.3 36.5, 180.9 a 156.1 50.3, 483.9 0.52 0.13, 2.08 9 96.7 50.3, 185.9
4559 a 377.6 237.9, 599.3 a 1077.6 709.5, 1636.5 0.35 0.19, 0.65 40 587.5 430.9, 800.9
60+ 17 1247.83 775.7, 2007.2 16 2271.5 1391.6, 3707.8 0.55 0.28, 1.09 33 1596.7 1135.1, 2246.0
Total 41 303.4 223.4, 412.0 41 878.3 646.7, 1192.8 0.35 0.22, 0.53 82 451.0 363.2, 560.0

General population

2044 14 38.5 22.8, 65.0 8 85.4 42.7, 170.8 0.45 0.19, 1.07 22 48.1 31.7, 73.0
4559 78 326.8 261.8, 408 70 697.0 551.4, 881.0 0.47 0.34, 0.65 148 436.4 371.5, 512.7
60+ 90 1318.5 1072.4, 1621.1 70 1915.3 1515.3, 2420.9 0.69 0.50, 0.94 160 1526.6 1307.5, 1782.5
Total 182 271.4 234.7, 313.8 148 641.8 546.3, 754.0 0.42 0.34, 0.53 330 366.1 328.7, 407.8

a=Suppressed to protect condentiality.

prevalence of IHD (PR 0.32; 95% CI: 0.290.36), while in
persons aged 60 years, women had a 34% lower prevalence
of IHD (PR 0.66; 95% CI: 0.600.73).
3.4. Incidence (Denition N)
We identied 82 incident cases of IHD and 330 incident
cases of IHD in the general population (Table 1). In 2005,
the age-standardized incidence of IHD was 754.7 (95% CI:
335.61173.7) per 100,000 persons per year in the MS
population and was 436.9 (95% CI: 292.6581.2) in the
controls. Over the period from 1989 to 2005, the incidence
rate of IHD was 24% higher in the MS population (IRR 1.24;
95% CI: 0.971.59). The incidence of IHD was lower in
women than men (Table 3). After adjusting for age, year
and MS status, women had a 46% lower risk of IHD (IRR 0.54;
95% CI: 0.440.65).
Based on the rst IHD claim, the mean (SD) age of onset
of IHD in the MS population was 58.1 (11.5) years versus 59.7
(11.4) years in the general population; the earliest age of
onset was 25 years in the MS population and 37 in the
general population but the latest age of onset was 85 years
in the MS population and 93 years in the controls. The
incidence of IHD increased with age in both populations
(Table 3). As compared to persons aged 2044 years, the
incidence rate of IHD was 7-fold higher in persons aged 45
59 years (IRR 7.70; 95% CI: 5.2311.3) and more than 50-fold
higher in persons aged 60 years (IRR 59.0; 95% CI: 27.3
128.7). The wide CIs reect the small numbers of affected
individuals in some cells.
In a stratied regression model, the incidence of IHD was
similar among persons aged 60 years in the MS population as
in the controls (IRR 1.04; 95% CI: 0.691.56), consistent with
the ndings for prevalence and suggesting that the overall
increased incidence was driven by the ndings in those aged
o60 years. Unlike prevalence, the incidence of IHD did not
differ between the MS and controls for persons aged 2044
years (IRR 2.01; 95% CI: 0.944.30) or 4559 years (IRR 1.33;
95% CI: 0.951.86) as compared to the controls; however,
the number of incident cases in the MS population was
small in these age groups, making it difcult to draw rm
conclusions.
Although the incidence of IHD varied from year to year,
there was no change over time (IRR 1.00; 95% CI: 0.981.03)
in either population.
Prevalence and incidence of ischemic heart disease in multiple sclerosis
4. Discussion
Published studies have been inconsistent as to whether
persons with MS are at increased or decreased risk for IHD
(Fleming and Blake, 1994; Koch-Henriksen et al., 1998;
Allen et al., 2008). After validating and applying an admin-
istrative case denition for IHD we found that more than
5% of the MS population has IHD. Earlier studies have
evaluated the prevalence of heart disease in persons with
MS, although this was not necessarily restricted to IHD.
In 2006, 6.9% (606/8893) of American participants in the
North American Research Committee on Multiple Sclerosis
(NARCOMS) Registry self-reported heart disease (Marrie et al.,
2008). A study examining the use of disease-modifying therapy
in 1807 persons with MS identied in an American claims
database reported that 7.53% had heart disease (Ozminkowski
et al., 2004) similar to the prevalence of 5.9% we found in the
Manitoba MS population in 2005. However, a Taiwanese study
reported that only 0.8% of the MS population had IHD, but the
prevalence of IHD was also very low in their control population
(0.2%) (Kang et al., 2010).
We found that the incidence and prevalence of IHD were
higher in the MS population than the matched control
population for all age groups combined. This may reect
the high prevalence of diabetes, hypertension and hyperli-
pidemia in persons with MS (Marrie, 2012). Further, persons
with MS have a higher frequency of adverse health behaviors
such as smoking and low levels of physical activity than the
general population (Motl, 2005) and lower levels of physical
activity in MS have been associated with subclinical athero-
sclerosis which might be expected to place them at similar
or increased risks of IHD (Ranadive, 2012). The overall
higher rates of IHD were mainly due to higher rates in
persons aged o60 years. The incidence of IHD was 201%
higher among persons aged 2044 years, but this did not
reach statistical signicance, possibly because of the small
number of persons with IHD in this age group (9 in the MS
population, 22 in the controls). Our ndings raise the
possibility that IHD occurs earlier in MS, or is diagnosed
earlier in MS due to surveillance bias. The lack of increased
incidence of IHD in those with MS over age 60 years raise the
possibility that IHD is under-diagnosed in those with MS over
age 60 years, or that persons with MS are more likely to die
from competing causes of death before IHD is diagnosed.
Two American studies previously reported fewer than
expected hospitalizations for IHD among persons with MS.
In New York city, persons with MS aged 4084 years were less
likely to be hospitalized for IHD (OR 0.58, 95% CI: = 0.51
0.66) or MI (OR 0.78, 95% CI: = 0.640.96) than matched
hospital controls (Allen et al., 2008). Hospitalized elderly
Medicare patients with MS had reported fewer hospital
discharges for IHD than hospitalized persons without MS
(Fleming and Blake, 1994). Three Scandinavian studies had
opposing ndings, reporting an increased risk of MI. For
example, among hospitalized Swedes with MS born in the
period 19111940, the risk of MI was 6-fold higher than
expected (Lindegard, 1985). Among Swedes hospitalized for
a rst diagnosis of MS in 19872009, the subsequent risk of
MI was 1.85-fold higher than expected when compared to
matched controls (Jadidi et al., in press). In Denmark, the
risk of MI was increased during the rst year after MS
diagnosis (IRR 1.84; 95% CI: 1.282.65) but declined
359
thereafter (IRR 1.10; 95% CI: 0.971.24) (Christiansen
et al., 2010). Given the relatively young age of onset of
MS in most affected persons, this was an unexpected
nding. These studies all differed from the present study
in their focus on hospitalized populations; thus prior studies
only captured IHD which severe enough to require hospita-
lization but not chronic, stable IHD. Future work should
examine the incidence and prevalence of IHD which does
and does not require hospitalization, and compare this in
the MS and general populations. This is important for two
reasons. First, in two other immune-mediated conditions,
rheumatoid arthritis and psoriasis (Crowson et al., 2005;
Gelfand et al., 2006) the risk of cardiovascular disease is not
fully explained by traditional risk factors such as hyperten-
sion, and the conditions themselves appear to indepen-
dently increase the risk of disease. In psoriasis the increased
risk of MI is particularly high among younger patients
(Gelfand et al., 2006). Second, the question of whether
IHD fails to be recognized more often in older persons with
MS is a pressing issue as survival improves and the MS
population ages (Bronnum-Hansen et al., 2004). In Alberta,
another Canadian province, IHD was the leading cause of
death after MS in 20002009 (Svenson et al., 2011). Evalu-
ating this issue would require direct examination of persons
with MS.
In the general population the incidence of acute MI, an
important component of IHD, has been declining (Fransoo
et al., 2009). We found that the incidence of IHD was stable
over time in both the MS and control populations but small
numbers of incident cases (n=82 in the MS population) limited
our detection of temporal trends. As we were unable to identify
any prior studies which examined temporal trends in the
incidence or prevalence of IHD in MS, replication of our ndings
is needed. The number of persons with MS who had incident IHD
in our sample was also too small to fully evaluate differences in
the age-specic disease incidence.
Administrative data may underestimate the presence of
comorbidities in persons with multiple chronic conditions due
to biases in coding, or when physicians can record only one
most responsible diagnosis per encounter (Elixhauser et al.,
1998; Canadian Institute for Health Information, 2003). Thus it
is important that the performance of administrative case
denitions for comorbidity be evaluated in the chronic disease
populations in which they will be used. All of the case
denitions tested for IHD in persons with MS was highly specic
when compared to medical records, exceeding 96%, which is
important to limit false positives (Table S1). Other studies of
specic diagnostic codes for IHD suggest that their specicity
and positive predictive value are high (Varas-Lorenzo et al.,
2008). Sensitivities of our case denitions were more modest
than specicities, potentially leading to underestimation of IHD,
but were still acceptable. Agreement between medical records
and administrative data was moderate to substantial in the MS
validation sample. Lix et al. (2008) compared some of the same
case denitions we evaluated to diagnoses of heart disease
reported by participants in the Canadian Community Health
Survey. For denition N (1 hospital or 2 physician in 5 years)
we found substantial agreement between the case denition
and our gold standard (=0.66 [95% CI: 0.420.90]), while Lix
had similar ndings (=0.55 [95% CI: 0.510.59]). This suggests
similar performance of the case denitions in the MS
and general populations, an important consideration when
360
comparing the incidence and prevalence of disease across
populations.
Aside from the small number of incident IHD cases among
persons with MS, another limitation of this study was that
medical records review for the validation cohort did not involve
all records of all health care providers; potentially contributing
to disagreement between data sources. Strengths of the study
included validation of the administrative case denition in a
population similar to that in which it would be applied (Marrie
et al., 2012a,b) the population-based design, use of data
covering hospitalizations and outpatient care, and use of a
longitudinal dataset covering more than 20 years.
5. Conclusions
Future studies should evaluate the performance of these and
potentially other administrative case denitions in the MS
population in other jurisdictions, and in other chronic disease
populations. Such evaluation is necessary to determine if the
performance characteristics of the case denitions are stable,
and to establish their use for pharmacovigilance. More than 5%
of the MS population had IHD, and the incidence of IHD was
higher than expected in persons aged o60 years. Further
evaluation of the possible increased risk of IHD in persons with
MS and the underlying mechanisms is warranted.
Conict of interest
Ruth Ann Marrie receives research funding from: Canadian
Institutes of Health Research, Public Health Agency of
Canada, Manitoba Health Research Council, Health Sciences
Centre Foundation, Multiple Sclerosis Society of Canada,
Multiple Sclerosis Scientic Foundation, Rx & D Health
Research Foundation, and has conducted clinical trials
funded by Sano-Aventis.
Nancy Yu receives research support from the Canadian
International Development Agency, the Multiple Sclerosis
Society of Canada, CIHR, and Manitoba Health and Healthy
Living.
Stella Leung reports no disclosures.
Lawrence Elliott receives research support from the
Canadian Institutes of Health Research, Health Sciences
Centre Foundation, Public Health Agency of Canada, and
the Multiple Sclerosis Society of Canada.
Patricia Caetano has worked on a research project funded
by Amgen.
Sharon Warren receives research funding from the CIHR,
the Canadian Health Services Research Foundation, Alberta
Health Services and SSHRC.
Christina Wolfson receives research funding from the
Multiple Sclerosis Society of Canada, Canadian Institutes
of Health Research, Canada Foundation for Innovation, and
Public Health Agency of Canada.
Scott Patten was a member of an advisory board for Servier,
Canada. He has received honoraria for reviewing investigator-
initiated grant applications submitted to Lundbeck and Pzer
and has received speaking honoraria from Teva and Lundbeck.
He is an associate editor for the Canadian Journal of Psychiatry
and a member of the editorial board of Chronic Diseases and
Injuries in Canada. He is the recipient of a salary support award
(Senior Health Scholar) from Alberta Innovates, Health Solutions
R.A. Marrie et al.
and receives research funding from the Canadian Institutes for
Health Research, the Institute of Health Economics and the
Alberta Collaborative Research Grants Initiative.
Larry Svenson reports no disclosures.
Helen Tremlett currently receives funding from: the
Multiple Sclerosis Society of Canada [Don Paty Career
Development Award]; US National MS Society [#RG 4202-
0A-2 (PI)]; Canadian Institutes of Health Research [MOP:
#190898 (PI) and MOP-93646 (PI)]; Michael Smith Foundation
for Health Research (Scholar award) and the Canada
Research Chair program. She has received speaker honoraria
and/or travel expenses to attend conferences from: the
Consortium of MS Centres, US National MS Society, Swiss
Multiple Sclerosis Society, the University of British Columbia
Multiple Sclerosis Research Program, Teva Pharmaceuticals
and Bayer Pharmaceutical (honoraria declined) and
ECTRIMS. Unless otherwise stated, all speaker honoraria
are either donated to an MS charity or to an unrestricted
grant for use by her research group.
John Fisk is the Director of the endMS Atlantic Regional
Research and Training Centre which is funded by the Multi-
ple Sclerosis Society of Canada. He receives research
funding from the Canadian Institutes of Health Research
(CIHR) and in the past has received grants, honoraria and
consultation fees from AstraZeneca, Bayer, Biogen-Idec
Canada, Heron Evidence Development Limited, Hoffmann-
La Roche, MAPI Research Trust, Novartis, Sano-Aventis,
Serono Canada, and QualityMetric Incorporated.
James Blanchard receives research support from the
Multiple Sclerosis Society of Canada, CIHR, Bill & Melinda
Gates Foundation, Canadian International Development Agency
and the United States Agency for International Development.
Acknowledgments
This study was supported (in part) by operating and Don
Paty Career Development grants from the Multiple Sclerosis
Society of Canada, the Manitoba Health Research Council
and the Canadian Institutes of Health Research, and the Rx
& D Health Research Foundation. The funding source(s) had
no role in the study design, collection, analysis or inter-
pretation of the data, nor in the decision to submit the
article for publication. The results and conclusions pre-
sented are those of the authors. No ofcial endorsement by
Manitoba Health is intended or should be inferred.
CIHR Team in the Epidemiology and Impact of Comorbidity on
Multiple Sclerosis (by site): University of Manitoba (James
Blanchard MD, PhD; Patricia Caetano, PhD; Lawrence Elliott,
MD, MSc; Stella Leung, MSc; Ruth Ann Marrie, MD, PhD; Bo
Nancy Yu, MD, PhD; Yichuan Wei, MSc), Dalhousie University
(Virender Bhan, MBBS; John D. Fisk, PhD), University of Alberta
(Joanne Profetto-McGrath, PhD; Sharon Warren, PhD; Larry
Svenson, BSc); McGill University (Christina Wolfson, PhD);
University of British Columbia (Helen Tremlett, PhD); University
of Calgary (Scott Patten, MD, PhD).
Appendix A. Supporting information
Supplementary data associated with this article can be found
in the online version at http://dx.doi.org/10.1016/j.msard.
2013.03.001.
Prevalence and incidence of ischemic heart disease in multiple sclerosis
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