Arthritis Care & Research

Vol. 69, No. 1, January 2017, pp 67–74

DOI 10.1002/acr.22926
C 2016, American College of Rheumatology
V

SPECIAL THEME ARTICLE: COMORBIDITIES AND THE RHEUMATIC DISEASES

Risk of Cardiovascular Morbidity in Patients With

Psoriatic Arthritis: A Meta-Analysis of
Observational Studies
ARI POLACHEK,1 ZAHI TOUMA,2 MELANIE ANDERSON,3 AND LIHI EDER4

Objective. To assess the magnitude of risk of cardiovascular and cerebrovascular morbidity in patients with psoriatic arthri-
tis (PsA) compared with the general population through a systematic review and meta-analysis of observational studies.
Methods. We searched the Medline, Embase, and Cochrane databases, as well as abstracts archives from rheumatol-
ogy conferences. Observational studies that included a PsA diagnosis, cardiovascular or cerebrovascular outcomes,
and a comparison group of individuals without psoriasis and rheumatic diseases and were case–control, cross-
sectional, or cohort studies, were assessed by 2 researchers. We calculated weighted pooled summary estimates of the
maximally adjusted effect size estimates for cardiovascular and cerebrovascular diseases using the random-effects
model, and tested for heterogeneity using the I2 statistic.
Results. Eleven studies, comprising 32,973 patients with PsA, met the inclusion criteria. There was a 43% increased risk
of cardiovascular diseases in patients with PsA compared with the general population (pooled odds ratio [OR] 1.43 [95%
confidence interval (95% CI) 1.24–1.66]). The risk of incident cardiovascular events was increased by 55% (pooled OR
1.22–1.96). Morbidity risks for myocardial infarction, cerebrovascular diseases, and heart failure were increased by 68%,
22%, and 31%, respectively (pooled OR 1.68 [95% CI 1.31–2.15], pooled OR 1.22 [95% CI 1.05–1.41], and pooled OR 1.31
[95% CI 1.11–1.55], respectively). We identified significant heterogeneity in all main analyses (P < 0.001).
Conclusion. Cardiovascular and cerebrovascular morbidity are increased by 43% and 22%, respectively, in patients
with PsA compared with the general population.

INTRODUCTION (3–5). However, until recently, only a few studies assessed

Psoriasis is a chronic immune-mediated skin disease affecting
2–3% of the general population (1). Psoriatic arthritis (PsA)
affects 15–30% of patients with psoriasis (2). Both conditions,
collectively termed psoriatic disease, are strongly associated
with cardiometabolic abnormalities. The risk of developing
cardiovascular events in patients with psoriasis was found to
be approximately 40% higher than in the general population
Dr. Eder’s work was supported by the Krembil Foundation
and by a Canadian Institutes of Health Research fellowship
award.
1 supports the independent association between the disease,
Ari Polachek, MD: University of Toronto, Toronto Western
Hospital, Toronto, Ontario, Canada; 2Zahi Touma, MD, PhD:
University of Toronto, Toronto Western Hospital, Centre for
Prognosis Studies in the Rheumatic Diseases, Toronto,
Ontario, Canada; 3Melanie Anderson, MLIS: University
Health Network, Toronto, Ontario, Canada; 4Lihi Eder, MD,
PhD: University of Toronto, Women’s College Research Insti-
tute, Women’s College Hospital, Toronto, Ontario, Canada.
Dr. Polachek received fellowship grant support from
Janssen Canada (less than $10,000).
Address correspondence to Lihi Eder, MD, PhD, Suite
6326, Women’s College Research Institute, Women’s College
Hospital, 76 Grenville Street, Toronto, Ontario, M5S 1B2,
Canada. E-mail: lihi.eder@wchospital.ca.
Submitted for publication February 12, 2016; accepted
in revised form April 19, 2016.
the risk of developing cardiovascular events in patients with
PsA, and while most studies found a higher cardiovascular
risk in these patients, others reported cardiovascular rates
that were similar to the general population (6–9).
The high prevalence of metabolic abnormalities, such as
impaired glucose tolerance and atherogenic lipid profile, in
psoriatic patients significantly contributes to the cardiovas-
cular burden (10–12). Thus, meticulous consideration of
traditional cardiovascular risk factors is warranted in epide-
miologic studies attempting to estimate the relative cardio-
vascular risk related to PsA. In psoriasis, such information
especially severe psoriasis, and cardiovascular events
(3–5,13). This link is less established in PsA.
Estimation of the magnitude of cardiovascular risk in
patients with PsA is of significant interest. The large body
of literature about the elevated cardiovascular risk in
patients with rheumatoid arthritis (RA) led to recommen-
dations to modify clinical cardiovascular risk scores
according to the magnitude of the excess risk related to
RA (14). Currently, no specific recommendations for car-
diovascular risk prevention in patients with PsA exist,
and these patients are managed according to national
guidelines for the general population. This practice could
potentially lead to underestimation of the actual

67

68
Significance & Innovations
 This is the first meta-analysis that estimated the
magnitude of the risk of cardiovascular and cere-
brovascular diseases in patients with psoriatic
arthritis (PsA) compared with the general population.
 This work advances the literature by showing
that incident cardiovascular events are increased
by 55% among PsA patients, supporting the
notion that PsA is an independent risk factor for
cardiovascular disease.
 The magnitude of the elevated risk is similar to
that observed in patients with severe psoriasis.
cardiovascular risk (15). Therefore, quantification of the
excess cardiovascular risk in PsA has clinical implications
and is of considerable importance. To address this gap in
knowledge, we performed a systematic review (SR) and
meta-analysis of observational studies to estimate the mag-
nitude of the risk of incident and prevalent cardiovascular
and cerebrovascular diseases in patients with PsA com-
pared with the general population.
MATERIALS AND METHODS
Literature review: data sources and search strat-
egies. This SR was prepared with a protocol following the
Preferred Reporting Items for Systematic Reviews and Meta-
Analysis Protocols statement (16). We searched the Medline,
Embase, and Cochrane Central Register databases, from their
inception (1966, 1980, and 1982, respectively) to March 18,
2015, using a strategy designed by an experienced medical
librarian (MA) to find primary references. The search strat-
egy was constructed to find publications containing at least 1
term from each of 2 search blocks: 1) the terms “psoriasis,”
“psoriatic arthritis,” “spondyloarthritis,” or “seronegative
spondyloarthropathy” and 2) synonyms for cardiovascular
disease and cerebrovascular disease. The search was not lim-
ited by language of publication or by publication status.
Additional relevant publications were found by manual
inspection of abstracts archives from rheumatology con-
ferences (American College of Rheumatology annual
meetings from 2010 to 2015 and European League Against
Rheumatism annual meetings from 2001 to 2015).
Selection of studies. The task of screening all titles and
abstracts for potential inclusion was divided between 2
authors (AP and LE). Selected publications were retrieved
in full, and 2 reviewers (AP and LE) independently
assessed them for eligibility. To be included in the SR,
original studies needed to fulfill the following inclusion
criteria: be a case–control, cross-sectional, or cohort study;
assess patients with PsA; compare patients to individuals
without psoriasis and rheumatic conditions; evaluate
myocardial infarction (MI), stroke, transient ischemic
attack (TIA), angina, ischemic heart disease, or heart fail-
ure, or a composite of these cardiovascular outcomes.
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Polachek et al
Data extraction. Two authors (AP and LE) indepen-
dently extracted the data according to a standardized form.
Discrepancies were resolved by consensus and by the
involvement of a third author (ZT) if necessary. For each
study included, we recorded the following: year of publica-
tion, country in which the study population lived, study
design, source of the study population, sample size, PsA
case definition, outcome definition, statistical adjustments
for cardiovascular risk factors, mean age and sex distribu-
tion of patients, and unadjusted and adjusted effect size for
cardiovascular risk (odds ratio [OR] or relative risk [RR]). We
referred to the study as ‘‘clinic-based’’ when subjects were
recruited from inpatient or outpatient clinics. A study was
classified as ‘‘population-based’’ if subjects were recruited
from the general population using health administrative
databases or surveys. If raw data were missing from an arti-
cle, the authors were contacted by e-mail. If there was no
response from the corresponding author after 2 e-mails, the
publication was excluded from the analysis. If a study
reported end points of PsA cases and a range of possible
control groups, the most suitable control group was chosen.
Where .1 study reported on the same or largely overlap-
ping study populations for the same outcome, the study
with the greatest number of person-years of followup was
used. If this was not discernible, the study using the most
appropriate analysis relevant to this SR was used.
Definition of end points. The following end points
were analyzed: cardiovascular disease, defined as angina,
ischemic heart disease, coronary artery disease, MI, or a
combination of these outcomes; cerebrovascular disease,
defined as stroke or TIA; and heart failure. Within the car-
diovascular disease group, MI was also analyzed as a sepa-
rate end point. These diagnoses were based on data from
medical charts or health administrative databases or were
self-reported as reported in the original studies. Where
available, data for maximally adjusted risk estimates were
extracted from the studies included in the SR.
Quality scores. The methodologic quality of the studies
included in the SR was assessed according to the
Newcastle-Ottawa Scale (NOS), a validated 9-point scale
for evaluating the quality of nonrandomized studies in
meta-analyses (17). The risk of bias was assessed across 3
domains: selection (range 0–4 points), comparability (range
0–2 points), and outcome (range 0–3 points), which are
scored separately for cohort and case–control studies. The
quality assessment of the studies was conducted indepen-
dently by 2 reviewers (AP and LE), and disagreements
between the reviewers were resolved by consensus.
Statistical analysis. The meta-analysis was performed
using Comprehensive Meta Analysis software, version 2.0
(Biostat), and Review Manager software, version 5.3. To esti-
mate the pooled effect size, the maximally adjusted effect
size estimates (RR and OR) and reported 95% confidence
intervals (95% CIs) were log-transformed. The inverse vari-
ance method was then applied with the random-effects
models of DerSimonian and Laird to provide a conservative
estimate of the effect due to the expected heterogeneity of

Cardiovascular Morbidity in PsA
Figure 1. Flow diagram of the selection of studies.
the study populations and designs (18). All statistical tests
were 2-sided, with a significance level of P less than 0.05.
Statistical heterogeneity was assessed with the I2 statistic.
The I2 was interpreted as follows: 25–49% low heterogene-
ity, 50–74% moderate heterogeneity, and $75% high het-
erogeneity (19). The sources and magnitude of heterogeneity
were explored by conducting subgroup analyses. Studies
were stratified a priori by study setting (clinic-based and
population-based) and NOS quality score ($8 versus ,8). A
sensitivity analysis was conducted by including only stud-
ies that fully adjusted for demographics and traditional car-
diovascular risk factors. Additionally, we also performed a
separate analysis stratified by study design (cohort and
cross-sectional/case–control). Assessments of potential dif-
ferences in effect between subgroups were based on the chi-
square test for heterogeneity statistics between subgroups. A
jackknife sensitivity analysis was conducted to assess the
robustness of the results by repeating the analysis multiple
times with removal of a single study from the pooled group
of studies (20). We assessed the presence of publication bias
by visual inspection of the funnel-plot of study size versus
standard error, with formal statistical testing using Egger’s
regression test (21,22). Publication bias was considered to be
present if the funnel-plot was asymmetric or if the Egger’s
test P value was less than 0.1.
RESULTS
Literature search. From the databases initially searched,
we identified 8,602 references, after removal of 2,163
duplicates. An additional reference was identified in the
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69
abstracts archives search. After an initial screening, we chose
33 full-text articles and conference abstracts were chosen for
further review (Figure 1). Among these publications, 7 stud-
ies were excluded because they were reviews, 6 because
they did not include a control population without psoriasis
and rheumatic conditions, 5 because they did not assess any
of the study outcomes, 1 because it used the same cohort as
prior studies, and 3 because they did not include sufficient
information for the meta-analysis. Studies with significant
cohort overlap (e.g., in which multiple studies used the Gen-
eral Practice Research Database in overlapping periods) were
included only once (23,24). The study with the highest-
quality measure and most complete reporting was included
(24). A total of 11 studies were therefore included in the
meta-analysis (6–9,24–30).
The characteristics of each study are shown in Table 1.
The study designs were cross-sectional (6 studies) and
cohort (5 studies). The majority were population-based stud-
ies (8 studies) and the remaining were clinic-/hospital-based
(3 studies). Five studies were from North America, 5 were
from Northern Europe, and 1 was from the Middle East. The
sources of data for the case definition of the study population
and the outcomes were electronic medical codes (6 studies)
and reviews of medical records (4 studies) and patient
reports (1 study). Finally, 3 of the studies were published as
full-text articles, and the information for the meta-analysis
was obtained from their published-abstract format.
Overall risk of cardiovascular disease. Eleven studies
assessed the overall risk of cardiovascular disease
(6–9,24–30). At least 32,973 patients with PsA were studied.
One study reported a subgroup analysis of cardiovascular
events in PsA patients among psoriasis patients; however,
the total number of PsA patients included in the analysis was
not reported (27). Overall, the risk of cardiovascular diseases
was significantly increased (by 43%) in patients with PsA
compared with the general population (pooled OR 1.43 [95%
CI 1.24–1.66]) (Figure 2). Analysis of the 5 cohort studies
found that the risk of developing incident cardiovascular
events was 55% higher in patients than in the general popu-
lation (pooled RR 1.55 [95% CI 1.22–1.96]) (6,24,27,28,30).
When the analysis was limited to the 3 studies that fully
adjusted for demographics and cardiovascular risk factors,
the risk of developing cardiovascular events remained statis-
tically significant (pooled OR 1.84 [95% CI 1.12–3.02];
P 5 0.02). A sensitivity analysis was performed after exclud-
ing the 3 studies that were not published as full-text articles
(26,28,30), and the results were essentially similar (pooled
OR 1.49 [95% CI 1.19–1.87]). Substantial heterogeneity was
observed among studies (I2 5 83.3%, Q 5 60, P , 0.001).
There were no significant differences in the pooled ORs
when stratified by study design, source population, and NOS
quality score (Table 2). The sensitivity analysis for overall
cardiovascular events confirmed that the results were robust.
The pooled OR remained significantly increased when
studies were excluded one at a time, with the pooled OR
ranging from 1.27 to 1.46 and with the corresponding 95% CI
bounds remaining above 1. The funnel-plot appeared sym-
metric overall (Figure 3), and the result of Egger’s regression
test for asymmetry was not significant (P 5 0.53).
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70 Polachek et al

Table 1. Characteristics of included studies*

Patients, % NOS
Study No. No. PsA Event Event male/mean Adj. quality
(Ref.) Country design Setting patients controls ascertainment definition ascertainment age variables score

(29) Germany CS Clinic 98 1,044 CR CAD CR NA Age, sex 6

(9) US CS Pop. 3,066 12,264 AC IHD, CB, HF AC 50.7/49.7 Age, sex 7
(7) US CS Pop. 99 198 AC CAD, CB, HF AC NA Age, sex 7
(8) Canada CS Clinic 648 39,278 CR MI, AG, CR for patients 56.2/43.5 Age, sex 6
stroke, HF SR for controls
(28) US Cohort Clinic 734 1,468 CR MI AC for PsA NA Age, sex 7
SR for controls
(6) Denmark Cohort Pop. 607 4,003,265 AC MACE† AC NA Age, sex, 9
RF
(27) US Cohort Pop. NR 93,545 SR MI, stroke CR 0/NA Age, sex, 7
RF
(24) UK Cohort Pop. 8,706 81,573 AC MI, stroke AC 51/51.6 Age, sex, 9
RF
(26) Israel CS Pop. 3,161 15,805 AC IHD, stroke, HF AC 46.6/58.3 Age, sex 8
(25) Norway CS Pop. 338 50,468 CR AG, rev., SR 43/54.3 Age, sex 6
MI, stroke
(30) Sweden Cohort Pop. 16,039 269,815 AC ACS, stroke AC NA Age, sex 8

* PsA 5 psoriatic arthritis; adj. 5 adjusted; NOS 5 Newcastle-Ottawa Scale; CS 5 cross-sectional; CR 5 chart review; CAD 5 coronary artery disease;
NA 5 not applicable/not available; Pop. 5 population; AC 5 administrative code; IHD 5 ischemic heart disease; CB 5 cerebrovascular; HF 5 heart
failure; AC 5 administrative code; CAD 5 coronary artery disease; MI 5 myocardial infarction; AG 5 angina; SR 5 self-report; MACE 5 major adverse
cardiac events; RF 5 risk factor; rev. 5 revascularization.
† A composite outcome of MI, stroke, and cardiovascular death.

Myocardial infarction. Myocardial infarction was stud-
ied in 6 studies with at least 25,942 PsA patients
(8,24,25,27,28,30). Overall, there was a 68% increase in the
risk of MI in patients with PsA (pooled OR 1.68 [95% CI
1.31–2.15]) (Figure 2). The level of heterogeneity was high
(I2 5 90%, Q 5 50, P , 0.001). Analysis restricted to the 4
longitudinal cohort studies found that the risk of develop-
ing incident MI in patients with PsA was 57% higher than
that in the general population (pooled RR 1.57 [95% CI
1.19–2.06]) (24,27,28,30). No significant difference was
observed in the pooled OR between clinic-based and
population-based studies (P 5 0.97).
Cerebrovascular events and congestive heart failure.
Eight studies assessed the risk of cerebrovascular events
among PsA patients (7–9,24–27,30). These studies were
based on a total number of at least 31,594 PsA patients
(Figure 2). The degree of heterogeneity was lower than
that observed for the other outcomes (I2 5 58.9%, Q 5 17,
P 5 0.01). There was a 22% increase in the risk of cerebro-
vascular events in patients with PsA (pooled OR 1.22
[95% CI 1.05–1.41]) (Figure 2). In the analysis stratified by
study design, the pooled OR was higher in cohort studies
than in cross-sectional studies (OR 1.38 versus 1.1, respec-
tively; P 5 0.02) (Table 2). The risk of developing incident
cerebrovascular events was increased by 38% in patients
with PsA compared with the general population when the
analysis was restricted to the 3 cohort studies (pooled RR
1.38 [95% CI 1.25–1.52]) (24,27,30). The heterogeneity in
the direction and the magnitude of the effect among the 5
cross-sectional studies led to a nonsignificant pooled OR
for cerebrovascular events (pooled OR 1.11 [95% CI 0.95–
1.29]). No significant changes in the pooled OR were
observed after excluding the single clinic-based study
from the analysis. Four studies assessed the risk of heart
failure in PsA patients. There was a 31% increase in the
risk of heart failure in patients with PsA compared with
the general population (OR 1.31 [95% CI 1.11– 1.55]) (Fig-
ure 2) (7–9,26).
DISCUSSION
The association between psoriasis and cardiovascular
morbidity has been well established by 3 SRs and meta-
analyses (3–5). However, the link between PsA and car-
diovascular events is less defined. In this SR and meta-
analysis, we systematically assessed the risk of prevalent
and incident cardiovascular diseases in patients with PsA
to estimate the magnitude of this association. We found
that patients with PsA had a 43% higher risk of having (or
developing) cardiovascular diseases compared to non-
psoriatic individuals, while the risk of developing an inci-
dent cardiovascular event was 55% higher in PsA patients
compared with the general population. Furthermore, the
risk of each of the individual cardiovascular outcomes
was increased, including MI (68%), cerebrovascular dis-
eases (22%), and heart failure (31%) in PsA patients com-
pared with the general population.
All studies except one (25) found a significant increase in
the risk of MI in patients with PsA compared with the general
population. Comparing the results of this SR to the risk of
developing incident MI in patients with psoriasis as assessed
in a meta-analysis by Armstrong et al (3), the overall magni-
tude of the risk for incident MI found in this SR was similar
to that reported in patients with severe psoriasis (pooled RR
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Figure 2. Random-effects meta-analysis of the risk of developing cardiovascular events (A), myocardial infarction (B), cerebrovascular
71

events (C), and heart failure (D) in patients with psoriatic arthritis compared with controls. 95% CI 5 95% confidence interval.
Cardiovascular Morbidity in PsA
 21514658, 2017, 1, Downloaded from https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.22926 by University Autonoma De Nuevo Leon, Wiley Online Library on [28/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
72 Polachek et al

Table 2. Risk of cardiovascular events according to study population, design, and

quality*

Random effects,
Outcome No. pooled OR (95% CI) P

Cardiovascular event
All studies 11 1.43 (1.24–1.66)
Setting 0.73
Clinic-based 3 1.57 (0.91–2.70)
Population-based 8 1.42 (1.21–2.67)
Study design 0.38
Cohort 5 1.55 (1.22–1.96)
Cross-sectional 6 1.35 (1.12–1.63)
Quality score 0.84
$8 4 1.48 (1.38–1.57)
,8 7 1.24 (1.16–1.33)
Myocardial infarction
All studies 6 1.68 (1.31–2.15)
Setting 0.98
Clinic-based 2 1.70 (0.79–3.64)
Population-based 4 1.68 (1.31–2.15)
Study design 0.48
Cohort 4 1.58 (1.19–2.07)
Cross-sectional 2 1.98 (1.09–3.59)
Quality score 0.50
$8 2 1.58 (1.31–1.91)
,8 4 1.94 (1.10–3.43)
Cerebrovascular event
All studies 8 1.22 (1.05–1.41)
Setting 0.54
Clinic-based 1 0.90 (0.34–2.41)
Population-based 7 1.23 (1.05–1.43)
Study design 0.02
Cohort 3 1.38 (1.25–1.52)
Cross-sectional 5 1.11 (0.95–1.29)
Quality score 0.83
$8 3 1.21 (1.01–1.50)
,8 5 1.19 (0.90–1.56)

* OR 5 odds ratio; 95% CI 5 95% confidence interval.

1.7) but higher than the reported risk for mild psoriasis
(pooled RR 1.29), even though the CIs were overlapping. Sim-
ilarly, a positive association was found between heart failure
and PsA in all 4 studies, and in 3 of them the association was
statistically significant (8). A greater degree of variability in
the direction and magnitude of the effect was found in regard
to the risk of cerebrovascular events in PsA patients. Only
half of the studies found a significant increase in the risk of
cerebrovascular events in PsA patients (9,24,30). Cohort stud-
ies tended to report a positive association between PsA and
cerebrovascular events, which resulted in a significant asso-
ciation in the pooled analysis (24,27,30). The variability was
much higher in cross-sectional studies (7–9,25,26). The
cross-sectional studies tended to be smaller, which may par-
tially explain the lack of association due to insufficient
power. Another potential explanation is a weaker association
between PsA and cerebrovascular events. The magnitude of
association between cerebrovascular diseases and PsA
(pooled OR 1.22) was lower than the risk reported in a meta-
analysis by Armstrong et al for severe psoriasis (pooled RR
1.56) but slightly higher than mild psoriasis (pooled RR 1.12)
(3). Collectively, these findings suggest that individuals with
a higher burden of inflammation, as indicated by severe pso-
riasis and PsA, have a higher risk of cardiovascular and cere-
brovascular events.
It is now widely accepted that atherosclerosis, the under-
lying process resulting in cardiovascular events, is strongly
linked with chronic low-grade vascular inflammation that
results from an interaction between immune mechanisms
and metabolic abnormalities within the vessel wall (31,32).
Studies in patients with PsA found abnormalities in several
stages of atherogenesis compared to nonpsoriatic controls,
including endothelial dysfunction, arterial wall stiffness,
plaque formation, and, ultimately, clinical cardiovascular
events (33–37). A recent meta-analysis found higher carotid
intima-medial thickness, higher frequency of plaques, and
lower flow-mediated dilatation in patients with PsA com-
pared with controls (38). Moreover, the development of ath-
erosclerotic plaques is associated with higher levels of
musculoskeletal and systemic inflammation in patients

Cardiovascular Morbidity in PsA
Figure 3. Funnel-plot of 11 studies assessing cardiovascular
risk in patients with psoriatic arthritis compared with the gen-
eral population. Each dot represents an individual study. The
vertical line is the random-effects pooled estimate of the log
odds ratio (OR).
with PsA (8,39). Overall, these findings support the notion
that PsA should be considered an independent risk factor
for cardiovascular disease.
The 55% increase in the risk of incident cardiovascular
events in PsA patients highlights the limitations of current
risk stratification strategies that are based on clinical risk
algorithms, such as the Framingham Risk Score. These algo-
rithms were found to underestimate the actual cardiovascu-
lar risk in patients with chronic inflammatory conditions,
including psoriasis and PsA (40,41), as they do not consider
the independent risk inherent in the chronic inflammatory
process. Nevertheless, aggressive primary cardiovascular
risk prevention should be part of the standard of care in
patients with PsA. Longitudinal studies assessing strategies
for optimizing cardiovascular risk stratification and their
impact on outcomes are warranted.
Our SR has several limitations. We included both cross-
sectional studies and cohort studies, which contributed to
the heterogeneity in the pooled estimates to some extent.
However, the risk related to prevalent and incident cardio-
vascular events was reported separately for each of the out-
comes, except heart failure. These estimates provide a
comprehensive overview of the burden of cardiovascular dis-
ease in PsA patients and the additional contribution of PsA to
cardiovascular morbidity. Additional sources of heterogene-
ity included different clinical settings, case definitions of
PsA, definitions of outcomes, modes of events ascertainment,
and the degree of adjustment for potential confounders. As
expected, statistically significant heterogeneity in the results
was found. We used the random-effects model, as recom-
mended, to include an estimate of variability. Sources of vari-
ability were partially explored by performing a subgroup
analysis and analysis by study design; however, only for cere-
brovascular diseases was the study design found to have a
significant effect. Of note, unlike in psoriasis meta-analyses,
only 1 of the studies attempted to estimate cardiovascular
risk by PsA severity, and only 2 studies reported the baseline
PsA disease activity measures. Ogdie et al classified patients
by disease-modifying antirheumatic drug (DMARD) use and
found that cardiovascular risk was higher in the group of
patients who were not prescribed DMARDs (24). However,
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73
no data exist about the validity of DMARD use as a marker of
PsA disease severity. A recent cohort study found that higher
levels of disease activity predicted major cardiovascular
events in PsA (39); however, these data are unavailable in
administrative databases. The heterogeneous nature of PsA
and the lack of an accepted definition for PsA severity may
explain the lack of such stratification.
In summary, this SR and meta-analysis of observational
studies indicates that people with PsA have a 43% increased
risk of cardiovascular disease and a 55% increased risk of
developing incident cardiovascular events compared with
the general population. The increased cardiovascular risk
was observed for all cardiovascular outcomes, including MI,
cerebrovascular events, and heart failure. The magnitude of
the elevated risk was similar to that observed in patients with
severe psoriasis. These findings support the notion that PsA
is an independent risk factor for cardiovascular diseases.
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it crit-
ically for important intellectual content, and all authors approved
the final version to be submitted for publication. Dr. Eder had full
access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Study conception and design. Polachek, Touma, Eder.
Acquisition of data. Polachek, Touma, Anderson, Eder.
Analysis and interpretation of data. Polachek, Touma, Eder.
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