EVIDENCE-BASED DERMATOLOGY: STUDY

SECTION EDITOR: MICHAEL BIGBY, MD; ASSISTANT SECTION EDITORS: DAMIANO ABENI, MD, MPH; ROSAMARIA CORONA, DSc, MD;
URBÀ GONZÁLEZ, MD, PhD; ABRAR A. QURESHI, MD, MPH; HYWEL WILLIAMS, MSc, PhD, FRCP

Association of Psoriasis With Coronary Artery,

Cerebrovascular, and Peripheral Vascular
Diseases and Mortality
Srjdan Prodanovich, MD; Robert S. Kirsner, MD, PhD; Jeffrey D. Kravetz, MD;
Fangchao Ma, MD, PhD; Lisa Martinez, MD; Daniel G. Federman, MD

Objective: To examine the cardiovascular risk factors
in patients with psoriasis and the association between pso-
riasis and coronary artery, cerebrovascular, and periph-
eral vascular diseases.
Design: Observational study.
Setting: Large Department of Veterans Affairs hospital.
Patients: The study included 3236 patients with pso-
riasis and 2500 patients without psoriasis (controls).
Main Outcome Measures: Using International Classi-
fication of Diseases, Ninth Revision, Clinical Modification,
codes, we compared the prevalence of traditional cardio-
vascular risk factors and other vascular diseases as well as
mortality between patients with psoriasis and controls.
Results: Similar to previous studies, we found a higher
prevalence of diabetes mellitus, hypertension, dyslipid-
emia, and smoking in patients with psoriasis. After con-
trolling for these variables, we found a higher preva-
lence not only of ischemic heart disease (odds ratio [OR],
1.78; 95% confidence interval [CI], 1.51-2.11) but also
of cerebrovascular (OR, 1.70; 95% CI, 1.33-2.17) and pe-
ripheral vascular (OR, 1.98; 95% CI, 1.32-2.82) dis-
eases in patients with psoriasis compared with controls.
Psoriasis was also found to be an independent risk fac-
tor for mortality (OR, 1.86; 95% CI, 1.56-2.21).
Conclusions: Psoriasis is associated with atherosclero-
sis. This association applies to coronary artery, cerebro-
vascular, and peripheral vascular diseases and results in
increased mortality.
Arch Dermatol. 2009;145(6):700-703

Author Affiliations:
Departments of Dermatology
and Cutaneous Surgery
(Drs Prodanovich, Kirsner, and
Martinez) and Epidemiology
and Public Health (Dr Kirsner),
University of Miami Miller
School of Medicine, and
Department of Dermatology,
Miami Veterans Affairs Medical
Center (Dr Kirsner), Miami,
Florida; Departments of
Medicine, Veterans Affairs
Connecticut Health Care,
West Haven (Drs Kravetz and
Federman), and Yale University
School of Medicine, New Haven
(Drs Kravetz and Federman),
Connecticut; and
Epidemiologic Studies, Illinois
Department of Public Health,
Springfield, Illinois (Dr Ma).
P
SORIASIS IS A COMMON DISOR-
der, affecting nearly 2% to 3%
of the world’s population, in-
cluding 7 million Americans
and125millionpersonsworld-
wide.1 In addition to complaints related to
the effects of psoriasis on the skin, psoriasis
has a well-known association with arthritis,
depression, and lower quality of life.2-5 More
recently, psoriasis has also been shown to be
asystemicinflammatorycondition,withsimi-
larities to other inflammatory immune dis-
orders. Since the risk of myocardial infarc-
tion is increased in rheumatoid arthritis and
systemic lupus erythematosus,6,7 which are
both inflammatory conditions, attention has
beenfocusedontheassociationbetweenpso-
riasis, cardiovascular risk factors, and myo-
cardial infarction.8 The cardiovascular risk
factors of hypertension, diabetes mellitus,
obesity,smoking,anddyslipidemiahavebeen
found to be more prevalent in patients with
psoriasis,9-17 and obesity and diabetes have
been shown to be more prevalent in patients
withseverediseasethaninpatientswithmild
disease.14
Not only are cardiovascular disease risk
factors more prevalent, but even after these
risk factors are controlled for, psoriasis con-
fers an independent risk for myocardial in-
farction.18 The increased risk seems to be
even higher both in younger patients and
in patients with more severe disease. Fur-
thermore, psoriasis is associated with myo-
cardial infarction, and persons with se-
vere psoriasis, but not mild psoriasis, have
been shown to have increased mortality
compared with those without psoriasis.19
Although the emphasis has previously
been placed on cardiovascular risk factors
as well as on myocardial infarction, athero-
sclerosis is a systemic disease. It is reason-
able to assume that if myocardial infarc-
tion is increased in patients with psoriasis,
other manifestations of atherosclerosis, such
as cerebrovascular disease and peripheral ar-
terial disease, might also be increased. Stroke
is a leading cause of mortality, and many of
those who are fortunate enough to survive
are left with a functional disability: 15% to
30% are permanently disabled, and 20% re-
quire institutional care at 3 months after

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 stroke onset.20 Peripheral arterial disease, which can cause
symptomatic claudication and may lead to amputation, is Table 1. Baseline Characteristics of Patients
also associated with an increased risk of cerebrovascular With Psoriasis and Controls a
disease, myocardial infarction, and death.21 In this study,
Patients With Psoriasis Controls
we attempted to ascertain whether psoriasis is associated Characteristic (n = 3236) (n =2500)
not only with coronary artery disease but also with the total
Age, mean (SD), y 67.9 (14.1) 65.1 (17.6)
atherosclerotic burden, including peripheral arterial dis-
Sex, male 95.5 88.2
ease and cerebrovascular disease. Diabetes 27.3 9.0
Hypertension 60.1 21.3
METHODS Dyslipidemia 31.6 9.6
Smoking 9.9 3.1
After approval by the Veterans Administration (VA) Institu- Mortality 19.6 9.9
tional Review Board and Development Committee at the Mi-
a For all characteristics, P ⬍ .01. Values other than age are expressed as
ami VA Medical Center, Miami, Florida, we conducted an ob-
servational study to evaluate the association between psoriasis percentages.
and vascular diseases (ischemic heart disease, peripheral arte-
rial disease, and cerebrovascular disease). We analyzed the com-
puterized records of all outpatients who were diagnosed be- Table 2. Odds of Vascular Disease in Patients
tween January 1, 1985, and December 31, 2005, at the Miami With Psoriasis Compared With Controls a
VA Medical Center as having psoriasis according to the an In-
ternational Classification of Diseases, Ninth Revision, Clinical Modi- Diagnosis OR a (95% CI)
fication (ICD-9-CM). A random list of 2500 patients (to assure Arteriosclerosis 2.18 (1.59-3.01)
sufficient statistical power) who were seen at the same facility Ischemic heart disease 1.78 (1.51-2.11)
during this period and who were without a coded ICD-9-CM Cerebral vascular disease 1.70 (1.33-2.17)
diagnosis of psoriasis were selected as controls. We estimated Peripheral vascular disease 1.98 (1.38-2.82)
study power based on a logistic regression model in which any Any vascular disease 1.91 (1.64-2.24)
vascular disease (yes or no) was the dependent variable and pso-
riasis diagnosis the independent variable. Assuming that the Abbreviations: OR, odds ratio; CI, confidence interval.
prevalence rate of any vascular disease in patients without pso- a The ORs were obtained after age, sex, hypertension, diabetes mellitus,

riasis was 25%, at a significance level of P⬍.05 and with a sample
size of 5236 observations (of which about 60% were patients
with psoriasis), this study would achieve 83% and 95% powers
to detect a change corresponding to odds ratios (ORs) of 1.20 and
1.25, respectively. A large study has documented an age-
adjusted OR of 1.28 for atherosclerosis alone in patients with pso-
riasis as compared with the control group (95% confidence in-
terval [CI], 1.04-1.59).9 We used frequency matching in control
selection to ensure similar distributions of diagnosis time be-
tween patients with psoriasis and controls in our study. In addi-
tion to demographic variables, using ICD-9-CM codes, we also
assessed for cardiovascular risk factors (hypertension, dyslipid-
emia, diabetes mellitus, and smoking), as well as for diagnoses
of ischemic heart disease, peripheral arterial disease, and cere-
brovascular disease. We identified patients with hypertension
(ICD-9-CM codes 401.00-405.9), diabetes mellitus (ICD-9-CM
codes 250.00-250.9), ischemic heart disease (ICD-9-CM codes
410.0-414.9 and 429.79) (but not dissecting aortic aneurysm or
coronary artery aneurysm), atherosclerosis (ICD-9-CM codes
440.0-440.9 and 443.9), cerebrovascular disease (ICD-9-CM codes
430.0-438.9, and peripheral arterial disease (ICD-9-CM codes
443.8-443.9) (but not other peripheral vascular disease). Smok-
ing status was determined by both ICD-9-CM codes and clinical
reminder data. The accuracy of ICD-9-CM codes has been vali-
dated within the VA.22 Patient outcomes were determined at the
end of the study period (December 31, 2006).
For univariate analysis, we performed a ␹2 test (discrete vari-
ables) or a t test (continuous variables) to compare demo-
graphic and clinical characteristics between patients with pso-
riasis and controls. To determine whether psoriasis was
independently associated with coronary artery disease, cerebro-
vascular disease, peripheral arterial disease, and all-cause mor-
tality, multivariate logistic regression analyses were performed,
with the diagnosis of psoriasis as the predictor in the model, and
age, sex, and comorbidities (including diabetes, dyslipidemia,
hypertension, and smoking) as covariates. All statistical analy-
ses were performed using SAS version 9.1 (SAS Institute Inc, Cary,
North Carolina), with a significance level of P⬍.05 (2-sided).
dyslipidemia, and tobacco use were controlled for.
RESULTS
A total of 3236 patients with psoriasis and 2500 con-
trols were identified in the Miami VA Medical Center elec-
tronic database. Most of the patients were men, with the
higher proportion of men in the psoriasis group (95.5%
vs 88.2% in controls; P⬍.01); patients with psoriasis were
older than controls (67.9 years vs 65.1 years; P⬍.01).
Major risk factors for vascular disease (diabetes melli-
tus, hypertension, dyslipidemia, and smoking) were sig-
nificantly more likely to be identified in the group of pa-
tients with psoriasis (Table 1). There was also a higher
percentage of deaths during the computerized observa-
tion period among patients with psoriasis than among
controls (19.6% vs 9.9%; P⬍ .01).
Multivariate analysis was performed to determine
whether psoriasis is independently associated with vas-
cular diseases. After age, sex, and history of hyperten-
sion, diabetes, dyslipidemia, and smoking status were con-
trolled for, patients with psoriasis were significantly more
likely than controls to carry a diagnosis of atherosclero-
sis (OR, 2.18; 95% CI, 1.59-3.01). Patients with psoria-
sis were also significantly more likely to have a concomi-
tant diagnosis of ischemic heart disease (OR, 1.78; 95%
CI, 1.51-2.11), cerebral vascular disease (OR, 1.70; 95%
CI, 1.33-2.17), or peripheral arterial disease (OR, 1.98;
95% CI, 1.38-2.82). Also, the combined vascular dis-
ease end point (ischemic heart disease, cerebral vascu-
lar disease, or peripheral arterial disease) was also sig-
nificantly more likely to be diagnosed in patients with
psoriasis than in controls (OR, 1.91; 95% CI, 1.64-2.24)
(Table 2).

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 Table 3. Vascular Disease and Mortality: Psoriasis and Traditional Cardiovascular Risk Factors
OR a (95% CI)
Risk Factor Peripheral Vascular Disease Ischemic Heart Disease
Hypertension 3.52 (2.44-5.07) 2.92 (2.48-3.44)
Diabetes 2.40 (1.84-3.13) 2.30 (1.96-2.70)
Dyslipidemia 1.81 (1.39-2.36) 2.39 (2.05-2.80)
Tobacco use 1.78 (1.20-2.63) 1.83 (1.42-2.37)
Psoriasis 1.98 (1.38-2.82) 1.78 (1.51-2.11)
Abbreviations: OR, odds ratio; CI, confidence interval.
a From logistic regression models that included age, sex, hypertension, diabetes mellitus, dyslipidemia, and tobacco use as the independent variables.
b Further adjusted for any vascular disease.
The likelihood and prevalence of arterial disease in pa-
tients with psoriasis appear to be similar to other well-
established risk factors for vascular disease in the mul-
tivariate analysis. The OR for the diagnosis of peripheral
arterial disease in patients with psoriasis (OR, 1.98; 95%
CI, 1.38-2.82) was greater than the OR for the diagnosis
of peripheral arterial disease in patients with dyslipid-
emia (OR, 1.81; 95% CI, 1.39-2.36) and smoking status
(OR 1.78; 95% CI, 1.20-2.63). Patients with hyperten-
sion (OR, 3.52; 95% CI, 2.44-5.07) and diabetes (OR, 2.40;
95% CI, 1.84-3.13) were more likely than patients with
psoriasis to be diagnosed as having peripheral arterial dis-
ease. Using the combined end point of ischemic heart
disease, cerebral vascular disease, and peripheral arte-
rial disease, the OR in patients with psoriasis was in-
creased (OR 1.91; 95% CI, 1.64-2.24) almost as much as
with well-known traditional risk factors. Furthermore,
psoriasis was independently associated with increased
all-cause mortality (OR, 1.86; 95% CI, 1.56-2.21)
(Table 3).
COMMENT
Psoriasis is an inflammatory disease that is character-
ized by hyperproliferation of keratinocytes and aug-
mented blood flow stimulated by immune cells that
respond to a markedly altered milieu of cytokine ex-
pression.23 Recent recognition of the systemic inflam-
matory effects of this common skin disease, as well as
the overrepresentation of cardiovascular risk factors in
patients with psoriasis, has led investigators to study
the association between psoriasis and ischemic heart
disease.
We have found that patients with psoriasis experi-
ence a higher prevalence not only of ischemic heart dis-
ease but also of peripheral arterial disease and cerebro-
vascular disease. This result is not surprising, given the
systemic nature of atherosclerosis. It has tremendous and
far-reaching clinical implications, as all of these vascu-
lar conditions represent a major financial cost to the health
care system as well as a major cause of disability and death.
The latter finding was corroborated by our analysis,
whereby we concluded that psoriasis is an independent
risk factor for mortality; ie, we found a higher percent-
age of deaths among patients with psoriasis than among
patients without psoriasis (19.6% vs 9.9%; P⬍.01), con-
firming the work of Gelfand et al.19
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Cerebral Vascular Disease Any Vascular Disease Mortality b
3.32 (2.59-4.25) 3.21 (2.76-3.73) 1.13 (0.95-1.34)
2.08 (1.70-2.54) 2.38 (2.04-2.79) 1.27 (1.05-1.52)
1.56 (1.27-1.90) 2.16 (1.86-2.52) 0.35 (0.28-0.43)
1.78 (1.32-2.40) 2.14 (1.67-2.74) 0.80 (0.59-1.09)
1.70 (1.33-2.17) 1.91 (1.64-2.24) 1.86 (1.56-2.21)
Several limitations to our study should be noted. Our
study used ICD-9-CM codes to determine whether cer-
tain health conditions were present. We cannot assume
that coding was both comprehensive and accurate. How-
ever, we have no reason to believe that differences in cod-
ing accuracy would exist between the patients with pso-
riasis and the controls. Furthermore, the prevalence rates
of vascular diseases in our cohorts are for known vascu-
lar disease. True prevalence, including subclinical dis-
ease, may be much higher. For example, in the general
population, it is known that nearly three-quarters of pe-
ripheral arterial disease is subclinical.24 Another limita-
tion is that we used a cross-sectional design; therefore,
we were restricted from assessing the temporal relation-
ship between psoriasis and vascular disease. Because ex-
isting medical records were used, data on tobacco use may
be incomplete and underestimated and may account for
the finding that tobacco use was not significantly asso-
ciated with mortality (95% CI, 0.59-1.09). While it is pres-
ently not known whether aggressive treatment of either
cardiovascular risk factors or psoriasis per se will lead
to an improvement in total atherosclerotic burden in cases
of psoriasis, a retrospective study has shown decreased
rates of vascular disease in patients with psoriasis or rheu-
matoid arthritis who have used methotrexate, espe-
cially in low cumulative doses.25
We hope that future prospective, randomized, con-
trolled studies using systemic therapy for psoriasis or
aggressive traditional risk factor management will
answer these questions more definitively. In the mean-
time, we recommend that health care providers who are
caring for patients with psoriasis be vigilant with
respect to traditional risk factor screening.26 Many of
these patients are cared for solely by dermatologists. It
would be prudent for dermatologists to be familiar with
suggested screening for cardiovascular risk factors and
recommendations for aspirin use. If not, it is imperative
that they work in collaboration with a primary care pro-
vider or another internal medicine specialist, who also
needs to be aware of our findings. Clinicians caring for
patients with this skin disorder should use a lower
threshold when considering testing for peripheral arte-
rial disease, carotid disease, or coronary artery disease
in those with typical or atypical symptoms.27 The ben-
efit of screening asymptomatic patients with psoriasis
for vascular disease is untested. While the association
between psoriasis and total atherosclerotic burden is
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 Section Editor’s Note
In this case-control study using Veterans Administra-
tion data, the authors concluded that patients with pso-
riasis are more likely to have cardiovascular, cerebro-
vascular, and peripheral vascular disease and mortality
than patients without psoriasis. Ascribing a causal rela-
tionship between psoriasis and these events is an inter-
pretation of the collected data. Features of case-control
studies that strengthen the validity of attributing a causal
relationship include that the study is free of bias and has
a strong association (ie, high odds ratio), a dose-
response gradient, consistency among studies, and bio-
logic plausibility.1 Studies using different databases by
and large have had similar results, and the recognition
of the role of inflammation on the development of ath-
erosclerosis lends biologic plausibility.2 The baseline
prevalences of risk factors for the development of vas-
cular disease in patients with psoriasis and controls were
quite different. Therefore, the resultant odds ratios should
be interpreted with caution. Although the odds ratios in
this study (1.7-2.2) are not particularly “high,” they are
clinically significant because the events described (vas-
cular disease and mortality) are frequent in the popula-
tion studied (ie, nearly doubling the risk of these events
has important public health implications).
1. Bigby M. Odds ratios and relative risks. Arch Dermatol. 2000;136(6):
770-771.
2. Kimball AB, Gladman D, Gelfand JM, et al. National Psoriasis Founda-
tion. National Psoriasis Foundation clinical consensus on psoriasis co-
morbidities and recommendations for screening. J Am Acad Dermatol.
2008;58(6):1031-1042.
becoming clearer, we look forward to future studies to
better answer the multitude of questions that arise as
new discoveries are brought forward.
Accepted for Publication: October 23, 2008.
Correspondence: Robert S. Kirsner, MD, PhD, Depart-
ment of Dermatology and Cutaneous Surgery, Univer-
sity of Miami Miller School of Medicine, 1600 NW 10th
Ave, RMSB, Room 2023-A, Miami, FL 33136 (rkirsner
@med.miami.edu).
Author Contributions: Dr Kirsner had full access to all
the data in the study and takes responsibility for the in-
tegrity of the data and the accuracy of the data analysis.
Study concept and design: Prodanovich, Kirsner, and Mar-
tinez. Acquisition of data: Prodanovich and Kirsner. Analy-
sis and interpretation of data: Kirsner, Kravetz, Ma, and
Federman. Drafting of the manuscript: Federman. Criti-
cal revision of the manuscript for important intellectual con-
tent: Prodanovich, Kirsner, Kravetz, Ma, and Martinez.
Statistical analysis: Kravetz and Ma. Administrative, tech-
nical, and material support: Prodanovich and Kirsner. Study
supervision: Kirsner.
Financial Disclosure: None reported.
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