Article

Prevalence of cardiovascular risk factors in patients with psoriasis

Dermatology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Journal of the American Academy of Dermatology (Impact Factor: 4.45). 12/2006; 55(5):829-35. DOI: 10.1016/j.jaad.2006.08.040
Source: PubMed
ABSTRACT
Previous studies suggest that patients hospitalized for psoriasis have an increased frequency of a variety of cardiovascular comorbidities. Limited population-based data exist on this association, and few studies have determined which factors are independently associated with psoriasis.
We sought to determine whether the prevalence of the major cardiovascular risk factors was higher in mild and severe psoriasis than in patients without psoriasis.
We conducted a population-based study in the United Kingdom using the General Practice Research Database. Patients were classified as having severe psoriasis if they received a code for psoriasis as well as systemic therapy. Patients were defined as having mild psoriasis if they ever received a psoriasis code but no systemic therapy. Control subjects were selected from the same practices and start dates as psoriasis patients. Patients were classified as having risk factors if they received codes for diabetes, hypertension, hyperlipidemia, obesity, or smoking. Analyses were performed by using conditional logistic regression, and adjustments were made considering age, gender, person-years, and all cardiovascular risk factors.
We identified 127,706 patients with mild psoriasis and 3854 with severe psoriasis. Respective prevalence rates of risk factors in those with severe psoriasis, mild psoriasis, and in controls were as follows: diabetes (7.1%, 4.4%, 3.3%), hypertension (20%, 14.7%, 11.9%), hyperlipidemia (6%, 4.7%, 3.3%), obesity (20.7%, 15.8%, 13.2%), and smoking (30.1%, 28%, 21.3%). Patients with mild psoriasis had a higher adjusted odds of diabetes (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.18]), hypertension (OR, 1.03; 95% CI, 1.01-1.06), hyperlipidemia (OR, 1.16; 95% CI, 1.12-1.21), obesity (OR, 1.27; 95% CI, 1.24-1.31), and smoking (OR, 1.31; 95% CI, 1.29-1.34) than controls. Patients with severe psoriasis had a higher adjusted odds of diabetes (OR, 1.62; 95% CI, 1.3-2.01), obesity (OR, 1.79; 95% CI, 1.55-2.05), and smoking (OR, 1.31; 95% CI, 1.17-1.47) than controls. Additionally, diabetes (OR, 1.39; 95% CI, 1.22-1.58) and obesity (OR, 1.47; 95% CI, 1.32-1.63) were more prevalent in those with severe psoriasis than with mild psoriasis.
The study was cross-sectional and therefore the directionality of the associations could not be determined.
Multiple cardiovascular risk factors are associated with psoriasis. Cardiovascular risk factors that are key components of the metabolic syndrome are more strongly associated with severe psoriasis than with mild psoriasis.

Full-text

Available from: Andrea B Troxel, Jan 06, 2014
Prevalence of cardiovascular risk factors
in patients with psoriasis
Andrea L. Neimann, MD,
a,b
Daniel B. Shin, BA,
a
Xingmei Wang, MS,
b
David J. Margolis, MD, PhD,
a,b
Andrea B. Troxel, ScD,
b
andJoelM.Gelfand,MD,MSCE
a,b
Philadelphia, Pennsylvania
Background: Previous studies suggest that patients hospitalized for psoriasis have an increased frequency
of a variety of cardiovascular comorbidities. Limited population-based data exist on this association, and
few studies have determined which factors are independently associated with psoriasis.
Objective: We sought to determine whether the prevalence of the major cardiovascular risk factors was
higher in mild and severe psoriasis than in patients without psoriasis.
Methods: We conducted a population-based study in the United Kingdom using the General Practice
Research Database. Patients were classified as having severe psoriasis if they received a code for psoriasis as
well as systemic therapy. Patients were defined as having mild psoriasis if they ever received a psoriasis code
but no systemic therapy. Control subjects were selected from the same practices and start dates as psoriasis
patients. Patients were classified as having risk factors if they received codes for diabetes, hypertension,
hyperlipidemia, obesity, or smoking. Analyses were performed by using conditional logistic regression, and
adjustments were made considering age, gender, person-years, and all cardiovascular risk factors.
Results: We identified 127,706 patients with mild psoriasis and 3854 with severe psoriasis. Respective
prevalence rates of risk factors in those with severe psoriasis, mild psoriasis, and in controls were as
follows: diabetes (7.1%, 4.4%, 3.3%), hypertension (20%, 14.7%, 11.9%), hyperlipidemia (6%, 4.7%, 3.3%),
obesity (20.7%, 15.8%, 13.2%), and smoking (30.1%, 28%, 21.3%). Patients with mild psoriasis had a higher
adjusted odds of diabetes (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.18]), hypertension (OR,
1.03; 95% CI, 1.01-1.06), hyperlipidemia (OR, 1.16; 95% CI, 1.12-1.21), obesity (OR, 1.27; 95% CI, 1.24-1.31),
and smoking (OR, 1.31; 95% CI, 1.29-1.34) than controls. Patients with severe psoriasis had a higher
adjusted odds of diabetes (OR, 1.62; 95% CI, 1.3-2.01), obesity (OR, 1.79; 95% CI, 1.55-2.05), and smoking
(OR, 1.31; 95% CI, 1.17-1.47) than controls. Additionally, diabetes (OR, 1.39; 95% CI, 1.22-1.58) and obesity
(OR, 1.47; 95% CI, 1.32-1.63) were more prevalent in those with severe psoriasis than with mild psoriasis.
Limitations: The study was cross-sectional and therefore the directionality of the associations could not be
determined.
Conclusion: Multiple cardiovascular risk factors are associated with psoriasis. Cardiovascular risk factors
that are key components of the metabolic syndrome are more strongly associated with severe psoriasis than
with mild psoriasis. ( J Am Acad Dermatol 2006;55:829-35.)
P
soriasis is a common chronic immune-
mediated disease that affects 1% to 3% of
the population.
1-3
It affects people of all ages,
and its incidence peaks in early adult life (20s) and
then again in later adult life (50s and 60s).
3-6
Clinical
manifestations of psoriasis are heterogeneous, rang-
ing from limited disease to very extensive disease.
Presentations of the skin lesions vary throughout life,
and there may be periods of remissions and exacer-
bations. The majority of patients (approximately
80%) have limited disease (eg, \2% body surface
area [BSA]), whereas approximately 20% of patients
have more extensive skin involvement (eg, [3%
From Dermatology
a
and the Center for Clinical Epidemiology and
Biostatistics,
b
University of Pennsylvania.
Supported by grant K23 AR051125-01 from the National Institutes
of Health and the National Institute for Arthritis, Musculoskel-
etal, and Skin Diseases (to J. M. G.).
Conflicts of interest: None identified.
Accepted for publication August 20, 2006.
Reprint requests: Joel M. Gelfand, MD, MSCE, Department of
Dermatology, University of Pennsylvania, 3600 Spruce St, 2
Maloney Bldg, Philadelphia, PA 19104. E-mail: joel.gelfand@
uphs.upenn.edu.
Published online September 26, 2006.
0190-9622/$32.00
ª 2006 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2006.08.040
829
Page 1
BSA).
7
Despite the fact that psoriasis carries minimal
risk of mortality, it is associated with significant
morbidity and has substantial economic costs to
both patients and the health care system.
8
The impact
of psoriasis on quality of life may be significant even
if relatively limited BSA is involved.
9
The pathophysiology of psoriasis is characterized
by increased antigen presentation, increased cuta-
neous T lymphocyte activity, and the up-regulation
of type 1 help er T cytokines.
10-12
The etiology of
psoriasis is unknown, but evolving evidence suggests
psoriasis is a complex disorder caused by the inter-
action of multiple genes, the immune system, and
environmental factors. Although few environme ntal
factors have been definitively linked to chronic
plaque psoriasis, recent evidence suggests that smok-
ing and an elevated body mass index (BMI) may be
risk factors for the development of psoriasis.
13
Smoking and obesity are associated with psoriasis
and are also established cardiovascular risk factors.
14
In addition to smoking and obesity, several studies in
the literature suggest a high prevalence of cardio-
vascular risk factors (eg, diabetes, hypertension, and
hyperlipidemia) as well as cardiovascular disease
(CVD) in psoriasis patients.
15-23
A major limitation of
most of these studies is that they focus on highly
selected psoriasis patients, such as those hospitalized
for their disease. Since patients with multiple comor-
bidities (including smoking and alcohol use) are
more likely to be hospitalized, these studies may
have been limited by selection bias.
24
Additionally,
none of these studies performed multivariable mod-
eling to deter mine which cardiovascular risk factors
may be independently associated with psorias is.
The goal of our investigation was to perform a
broadly representative population-based study to
determine whether the prevalence of the major car-
diovascular risk factors identified by the Framingham
studies was higher in patients with mild and severe
psoriasis than in patients without psoriasis. We also
aimed to determine whether these risk factors were
independently associated with both mild and severe
psoriasis.
METHODS
Study design
This was a cross-sectional (prevalence) study
with data collected by general practitioners (GPs)
in the United Kingdom (UK), who were participating
in the General Practice Research Database (GPRD)
between 1987 and 2002. GPs were unaware of the
hypothesis to be tested. The data were collected
as part of the patient’s electronic medical record
and are maintained in the GPRD. GPRD contains
data on more than 9 million persons with more than
35 million person-years of follow-up time and is
broadly representative of the UK population.
25
In the
UK system of care, the GP is responsible for manag-
ing all aspects of a patients’ care. GPs refer patients to
specialists, and the infor mation from the specialist
is captured electronically by the GP.
26
GPs receive
specific training, financial inducements, and penal-
ties to ensure accuracy of the data. GPRD has been
used extensively for epidemiologic studies. The
validity of using the GPRD to study psoriasis and
diseases associated with cardiovascular disease has
been demonstrated previously.
1,26-30
Study population
The study population consisted of all psoriasis
patients who had at least one day of observation
time, as described previously.
31
Each psoriasis pa-
tient was matched to up to 5 subjects (as available
based on matching criteria) who did not have pso-
riasis, who were seen in the same practi ce, and who
had a date of observation in the practice (the max-
imum of the date when the patient registered with
the practice and the date when the practice was
designated ‘‘up to standard’’) within 60 days. Prac-
tices are designated as being ‘‘up to standard’’ when
audits demonstrate that at least 95% of relevant
patient encounters are recorded and the data are
determined to be of suitab le quality fo r epidemio-
logic research. The matching was performed to
ensure that pati ents were followed up in the same
practice and time periods to minimize the impact of
secular and geographic differences between those
with and without psoriasis. The analyses were re-
stricted to patients 20 to 90 years of age as cardio-
vascular risk fac tors are very rare in patients younger
than 20 years, which diminished the number of
eligible controls for this study.
Definition of prevalence
Prevalence is defined as the proportion of indi-
viduals in a population who have the disease of
interest in a specified time period. Our definition of
prevalence approximates lifetime prevalence as any
Abbreviations used:
BMI: body mass index
BSA: body surface area
CI: confidence interval
CVD: cardiovascular disease
GP: general practitioner
GPRD: General Practice Research Database
JNK: c-Jun amino-terminal kinase
OR: odds ratio
T
H
1: type 1 helper T cells
TNF: tumor necrosis factor
JAM ACAD DERMATOL
NOVEMBER 2006
830 Neimann et al
Page 2
documentation of psoriasis or cardiovascular risk
factors (diabetes, hypertension, hyperlipidemia,
smoking, increased BMI) by the GP at the time the
patient was registered in the practice would result in
the patient being classified as having these diseases.
In addition, documentation of these diseases could
occur at any time that the patient was followed up in
the practice over the 5 to 6 years of observation time.
Study time period
For all patients, observation start-time was the
maximum of patient registration and ‘‘up-to-standard’’
dates. Follow-up time ended when patients died,
transferred out of the practice, or the practice was no
longer ‘‘up to standard’’ (whichever came earliest).
Definition of psoriasis
Diseases are class ified in the GPRD using Oxford
Medical Information System and Read codes. Oxford
Medical Information System and Read codes are
diagnostic codes that GPs use as part of the patient’s
electronic medical record. Patients were classified as
having psoriasis if they ever received a diagnostic
code for psoriasis by the GP that has been validated
in previous studies.
1,28,29
For example, the epidemiol-
ogy of psoriasis in GPRD is very similar to other
population-based studies in the United Kingdom,
32
and more than 90% of patients with a psoriasis
diagnostic code receive psoriasis therapies.
1
Addi-
tionally, when directly querying a random sample
of 100 GPs who had entered a diagnostic code of
psoriasis, in approximately 90% of cases the GPs
confirmed that psoriasis was still the diagnosis after 4
years of follow-up.
28
Psoriasis patients were defined
as having ‘‘severe’’ disease if they received a treatment
code consistent with severe disease (eg, psoralen,
phototherapy, methotrexate, azathioprine, cyclospor-
ine, etretinate, acitretin, hydroxyurea, mycopheno-
late) during the entire study time period. Treatments
consistent with severe psoriasis were determined by
the British National Formulary and the opinion of two
dermatologists (D. J. M., J. M. G.). Psoriasis patients
were classified as having ‘‘mild’’ disease if they
received a code for psoriasis but never received a
prescription code consistent with severe disease dur-
ing the study period. Patients were classified as not
having psoriasis (eg, control population) if they never
received a diagnostic code consistent with psoriasis.
Definition of cardiovascular risk
factors/comorbidit ies
Patients were classified as having a cardiovascular
risk factor if they received a medical code consistent
with diabetes, hypertension, hyperlip idemia, or cur-
rent smoking at any time during the study period.
The BMI was deter mined by weight and height
calculations or from documentation in the patient’s
electronic medical record.
Statistical analysis
The data were summarized descriptively. The
prevalence rates of cardiovascular risk factors in
the psoriasis groups were first compared with those
in the nonps oriasis population using unadjusted
conditional logistic regression modeling, which
accounted for matching factors of practice and dif-
ferences in observation time. The rates were then
adjusted for age, sex, and person-years of observation
to yield prevalence odds ratios. To test the indepen-
dent association of individual cardiovascular risk
factors with both mild and severe psoriasis, we also
performed multivariable conditional logistic regres-
sion modeling, adjusting for each of the individual
risk factors (diabetes, hypertension, hyperlipidemia,
smoking, BMI) in addition to age, sex, and person-
years. All statistical analyses were performed using
Intercooled Stata 8.2 (Stata Corp, College Station, Tex).
Protection of study subjects
Data utilized for this study were stripped of
personally identifiable infor mation. The study was
approved by the Office of Regulatory Affairs of the
University of Pennsylvania and by the Scientific
and Ethical Advisory Group of the Medicines
Control Agency, United Kingdom. The study was
conducted in concordance with the Declaration of
Helsinki.
RESULTS
We identified 127,706 patients with mild psorias is
who were matched with 465,252 subjects without
psoriasis and 3854 patients with severe psoriasis
matched to 14,065 corresponding subjects without
psoriasis (Table I). Psoriasis patients were slightly
older than matched control patients and were more
likely to be male than the controls. In addition,
person-years of observation were slightly greater in
both psoriasis groups compared with their respec-
tive control groups (Table I). Information on BMI
was available for 61% of patients.
In unadjusted analyses, patients with mild and
severe psoriasis were more likely to be current
smokers and have diabetes, hypertension, hyperlip-
idemia, and increased BMI compared with controls
(Table I). Patients with mild psoriasis had increased
odds of having each of the cardiovascular risk factors
that persisted (Table II) when adjusting for age,
gender and person-years (diabetes: odds ratio [OR]
1.27, 95% confidence interval [CI] 1.23-1.31; hyper-
tension: OR 1.16, 95% CI 1.14-1.18; hyperlipidemia:
JAM ACAD DERMATOL
VOLUME 55, NUMBER 5
Neimann et al 831
Page 3
OR 1.28, 95% CI 1.24-1.33; smoking: OR 1.4, 95% CI
1.38-1.43; BMI 25-30: OR 1.12, 95% CI 1.10-1.14; BMI
[30: OR 1.29, 95% CI 1.26-1.32). The OR of mild
psoriasis after adjus ting for age, gender, person-
years, and each of the other comorbidities (Table III)
remained statistically significantly elevated in pa-
tients with diabetes (OR 1.13, 95% CI 1.08-1.18),
hypertension (OR 1.03, 95% CI 1.01-1.06), h yperlip-
idemia (OR 1.16, 95% CI 1.12-1.21), elevated BMI
(BMI 25-30: OR 1.12, 95% CI 1.10-1.14; BMI [30: OR
1.27, 95% CI 1.24-1.31), and who were current
smokers (OR 1.31, 95% CI 1.29-1.34); however, the
magnitude of the association was small for hyper-
tension. Similar results were obtained via sensitivity
analysis in which we ensured that all patients were
seen at least twice by GPs and that their end of
observation time coincided with a GP visit (to ensure
that all patients were actively followed up) (data not
shown). Additionally, similar res ults were found
when performing a sens itivity analysis in which we
performed the multivariable model (except the BMI
variable) in the entire patient sample (data not
shown). Finally, similar results were found in a sen-
sitivity analysis that included a history of myocardial
infarction, indicating that the cardiovascular risk fac-
tors were not necessarily more likely to be identified in
psoriasis patients because psoriasis is associated with
CVD (eg, myocardial infarction) (data not shown).
In analysis of severe psoriasis, there was a statis-
tically significant association (Table II) between each
of the individual cardiovascular risk factors and
severe psoriasis after adjusting for age, gender, and
person-years (diabetes: OR 1.86, 95% CI 1.58-2.19;
hypertension: OR 1.25, 95% CI 1.13-1.39; hyperlip-
idemia: OR 1.31, 95% CI 1.11-1.56; elevated BMI
(BMI 25-30: OR 1.28, 95% CI 1.15-1.43; BMI [30: OR
1.84, 95% CI 1.60-2.11); current smokers: OR 1.31,
95% CI 1.20-1.44). This association persisted in the
Table I. Description of study groups
Variable Control—mild Mild Control—severe Severe
No. (%) 465,252 (78.46) 127,706 (21.54) 14,065 (78.49) 3,854 (21.51)
Sex
Male 218,269 (46.9) 61,472 (48.1) 6,555 (46.61) 1,883 (48.86)
Female 246,983 (53.1) 66,234 (51.86) 7,510 (53.39) 1,971 (51.14)
Age (y)
Mean (median, 25th, 75th) 45.7 (42, 30, 60) 46.4 (44, 31, 60) 46.34 (43, 31, 61) 49.8 (49, 37, 63)
Person-years 5.57 6.06 5.87 6.86
Diabetes 15,161 (3.26) 5,564 (4.36) 457 (3.25) 272 (7.06)
Hyperlipidemia 15,297 (3.29) 6,024 (4.72) 501 (3.56) 232 (6.02)
Hypertension 54,840 (11.79) 18,718 (14.66) 1,855 (13.19) 769 (19.95)
Smoking 98,337 (21.14) 35,762 (28.00) 3,157 (22.45) 1,158 (30.05)
BMI 25-30* 90,619 (32.88) 29,759 (34.98) 2,799 (33.38) 994 (37.68)
BMI [30* 36,117 (13.1) 13,404 (15.75) 1,093 (13.03) 545 (20.66)
BMI, Body mass index.
*BMI was available in 61% of patients.
Table II. Prevalence odds ratios of individual
cardiovascular risk factors in mild and severe
psoriasis versus con trols
Variable
Mild psoriasis
model (95% CI)*
Severe psoriasis
model (95% CI)*
Diabetes 1.27 (1.23-1.31) 1.86 (1.58-2.19)
Hypertension 1.16 (1.14-1.18) 1.25 (1.13-1.39)
Lipids 1.28 (1.24-1.33) 1.31 (1.11-1.56)
Smoking 1.40 (1.38-1.43) 1.31 (1.20-1.44)
BMI 25-30
y
1.12 (1.10-1.14) 1.28 (1.15-1.43)
BMI [30
y
1.29 (1.26-1.32) 1.84 (1.60-2.11)
BMI, Body mass index; CI, confidence interval.
*Model adjusted for age, sex, person-years.
y
BMI was available in 61% of patients.
Table III. Prevalence odds ratios of individual
cardiovascular risk factors in patients with mild
and severe psoriasis versus controls
Variable
Mild psoriasis
model (95% CI)*
Severe psoriasis
model (95% CI)*
Diabetes 1.13 (1.08-1.18) 1.62 (1.3-2.01)
Hypertension 1.03 (1.01-1.06) 1.00 (0.87-1.14) NS
Lipids 1.16 (1.12-1.21) 1.04 (0.84-1.28) NS
Smoking 1.31 (1.29-1.34) 1.31 (1.17-1.47)
BMI (25-30)
y
1.12 (1.1-1.14) 1.27 (1.14-1.42)
BMI ([30)
y
1.27 (1.24-1.31) 1.79 (1.55-2.05)
BMI, Body mass index; CI, confidence interval; NS, not statistically
significant.
*Model adjusted for age, sex, person-years, diabetes, hypertension,
hyperlipidemia, smoking, and BMI.
y
BMI data were available in 61% of patients.
JAM ACAD DERMATOL
NOVEMBER 2006
832 Neimann et al
Page 4
case of diabetes, increased BMI, and current smok-
ing after adjusting for age, gender, person-years, and
all cardiovascular risk factors (Table III); however,
the association was attenuated and no long er statis-
tically significant in patients with hypertension (OR
1.00, 95% CI 0.87-1.14) and hyperlipidemia (OR 1.04,
95% CI 0.84-1.28). Similar results were obtained via
sensitivity analyses that excluded patients treated
with cyclosporine and oral retinoids (to ensure that
therapies that have been associated with hyperten-
sion and hyperlipidemia did not solely account for
reported associations between severe psoriasis and
these comorbidities) (data not shown) and in which
we assured that all patients were seen at least twice
by GPs and that their end of observation time
coincided with a GP visit (to ensure that all patients
were actively followed up) (data not shown). Addi-
tionally, similar results were found in performing
a sensitivity analysis in which we used the multivar-
iable model (except the BMI variable) in the entire
sample (data not shown). Finally, similar results were
found in a sensitivity analysis that included a history
of myocardial infarction, indicating that the cardio-
vascular risk factors were not necessarily more likely
to be identified in severe psoriasis patients because
severe psoriasis is associated with cardiovascular
disease (eg, myocardial infarction) (data not shown).
The strongest associations with severe psoriasis in
both adjusted analyses were with diabetes and obesity
(BMI [30). In addition, these two diseases were more
prevalentinpatientswithseverepsoriasisthaninthose
with mild psoriasis when adjusting for age, gender,
and person-years (diabetes: OR 1.39, 95% CI 1.22-1.58;
obesity: OR 1.47, 95% CI 1.32-1.63) (Table IV).
DISCUSSION
The results of this study suggest that diabetes,
hypertension, hyperlipidemia, smoking, and in-
creased BMI are associated with both mild and
severe psoriasis. Additionally, these d iseases are all
independently associated with mild psoriasis; how-
ever, except for obesity and smoking, the association
was negligible to modest for most of the cardiovas-
cular risk factors and therefore unlikely to be of
clinical significance. The association with severe
psoriasis when controlling for traditional cardiovas-
cular risk factors persists in the case of diabetes,
smoking, and increased BMI (especially BMI [30
[obesity]), but in the case of hypertension and
hyperlipidemia the association is attenuated, sug-
gesting that these latter two diseases are not inde-
pendently associated with severe psoriasis. In
addition, patients with severe psoriasis were more
likely to have each of the cardiovascular risk factors
we studied compared with patients who had mild
psoriasis, with the magnitude of association being
strongest for obesity, diabetes, and hypertension.
These results suggest that psoriasis is associated
with the complex disorder of metabolic syndrome,
which incorporates hypertension, dyslipidemia, obe-
sity, and impaired glucose tolerance, and that the
association is stronger for severe psoriasis compared
with mild psoriasis.
33
Similar to psoriasis, the metabolic syndrome is
characterized by increases in the immunological
activity of type 1 helper T cells (T
H
1), which suggests
the hypothesis that psoriasis ma y be associated with
the metabolic syndrome because of shared inflam-
matory pathways.
34
For example, circulatory levels
of tumor necrosis factor (TNF)-a, soluble TNF-a
receptors, and in vitro TNF-a production have been
shown to be elevated in patients with components of
the metabolic syndrome, such as obesity and insulin
resistance.
34,35
TNF may lead to insulin resistance by
inhibiting insulin-mediated tyrosine phosphoryla-
tion of the insulin receptor as well as insulin receptor
substrate-1, key to downstream insulin signaling and
glucose transportation to the cell surface.
36
Further-
more, TNF-a has also been shown to be a potent
activator of c-Jun amino-terminal kinase (JNK),
which stimulates activator protei n-1, a major regula-
tor of proinflammatory activity. Mouse models show
that JNK activity is abnormally elevated in obesity
and that the absence of the JNK1 molecule is asso-
ciated with decreased adiposity, improved insulin
sensitivity, and enhanced insulin receptor signal-
ing.
37
Therefore it is possible that the association of
the diseases which characterize the metabolic syn-
drome and psoriasis is explained by dysregulation of
T
H
1 pathways shared by these seemingly disparate
diseases. Another explanation for the predispos ition
of psoriasis patients to develop metabolic syndrome
may be that certain behaviors or the psychological
impact of psoriasis itself (eg, poor eating habits,
alcohol consumption, stress, decreased exercise due
Table IV. Prevalence odds ratios of individual
cardiovascular risk factors in severe versus
mild psoriasis
Variable Psoriasis model (95% CI)*
Diabetes 1.39 (1.22-1.58)
Hypertension 1.16 (1.07-1.26)
Hyperlipidemia 1.06 (1.05-1.07)
Smoking 1.07 (1.00-1.15)
BMI (25-30)
y
1.19 (1.09-1.30)
BMI ([30)
y
1.47 (1.32-1.63)
BMI, Body mass index; CI, confidence interval.
*Model adjusted for age, sex, person-years.
y
BMI data were available in 61% of patients.
JAM ACAD DERMATOL
VOLUME 55, NUMBER 5
Neimann et al 833
Page 5
to psoriasis symptoms or stigmatization) may lead
to development of increased body weight and the
metabolic syndrome. Lastly, the metabolic syndrome
itself could predispose an individual to developing
psoriasis as observed by a case-control study in
which increased BMI (a precursor to the metabolic
syndrome) was an independent risk factor for devel-
oping psoriasis (BMI 26-29: OR 1.6, 95% CI 1.1-2.1,
BMI[30: OR 1.9, 95% CI 1.2-2.8 while controlling for
age, sex, marital status, hospitalization, education
level, smoking, and alcohol use).
Our study also confirms several previous reports
that psoriasis is associated with smoking.
3
Nicotine
alters a wide range of immunological functions,
including innate and adaptive immune responses.
38,39
Nicotine can modulate the functional capacity of
dendritic cells and can increase the secretion of
proinflammatory T
H
1 cytokines by dendritic cells.
40,41
Studies support the hypothesis that nicotine alters
the immune response by directly interacting with
T cells and dendritic cells as well as indirectly through
brain-immune interactions.
42
Additionally, nicotinic
cholinergic receptors have been demonstrated on
keratinocytes that stimulate calcium influx and
accelerate cell differentiation; they can also control
keratinocyte adhesion and upward migration in the
epidermis.
43
This suggests a biologic explanation for
the association between smoking and psoriasis.
Our study advances the literature of the associa-
tion of psoriasis and cardiovascular risk factors. To
our knowledge, this study is the only broadly repre-
sentative population-based study to date examining
the prevalenc e of these combined cardiovascular
risk factors with psoriasis. Additionally, our study
examined patients with both mild and severe psori-
asis and utilized multivar iable modeling to deter-
mine which factors are independently associated
with psoriasis. The study is broadly representative of
all psoriasis patients; therefore the findings likely can
be generalized to the general population of patients
with psoriasis.
Observational studies may be limited by bias and
confounding. Selection bias is unlikely to explain the
results described herein because the psoriasis
patients and control subjects were identified and
included from the same well-defin ed source popu-
lation. Information (ascertainment) bias is unlikely
to explain the result s because psoriasis patients and
control subjects had information collected in the
same manner (ie, by GPs matched by practice), and
the result s were robust to sensitivity analysis in
which we ensured that all patients were actively
followed up. Completeness of data may be an issue
in epidemiologic studies. Information on BMI was
available in our study for about 61% of patients,
which could affect generalizability. However, we
thought this unlikely as our full multivariable anal-
ysis (adjusting for age, sex, person-years, and each
of the cardiovascular risk factors except for BMI) in
our entire study population was comparable to our
analysis of only our population in which data on
BMI were captured. Furthermore, we measured
smoking status as ‘‘current’’ or ‘‘never’’ and therefore
could not determine whether history of smoking or
number of cigarettes smoked introduced any poten-
tial confounding. In addition, we defined severe
psoriasis based on a history of having received
systemic therapies; therefore we cannot differentiate
between the impact of psoriasis severity and sys-
temic therapy. The most commonly used systemic
therapy was methotrexate, and to our knowledge
methotrexate has no known association with diabe-
tes, hypertensio n, hyperlipidemia, or smoking. Oral
retinoids and cyclosporine may induce certain car-
diovascular risk factors such as hypertension and
hyperlipidemia in some patients; however, our find-
ings in the sever e psoriasis group were robust to
sensitivity analyses, which excluded pati ents treated
with cyclosporine and oral retinoids. We also did not
directly assess psoriasis activity in our mild psoriasis
group, which is likely heterogeneous; therefore it is
possible that the associati on with cardiovascular risk
factors in those we classified as having mild psoriasis
varies on the basis of psoriasis activity (eg, extent of
skin involvement). Finally, since the diagnosis of
psoriasis was based on GP diagnosis, it is possible
that some patients with mild psoriasis did not in fact
have psoriasis. In the event that misclassification of
psoriasis occurred, we believe this would bias our
results toward the null, thus making our positive
findings even stronger.
The findings of this study are important and add
to the growing evidence that dia betes, hypertension,
hyperlipidemia, smoking, and increased BMI are
associated with psoriasis. In particular, the results
of this study demonstrate that psoriasis is associated
with key components of the metabolic syndrome and
that this association is stronger in patients with severe
psoriasis compared with those with mild psoriasis.
This finding is import ant since those with as little as
one or two metabolic syndrome risk factors are at
increased risk for death caused by CVD.
44
Therefore,
as part of good medical care, patients with psoriasis
should be encouraged to identify and manage their
modifiable cardiovascular risk factors.
REFERENCES
1. Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA,
Margolis DJ. Prevalence and treatment of psoriasis in the
United Kingdom: a population-based study. Arch Dermatol
2005;141:1537-41.
JAM ACAD DERMATOL
NOVEMBER 2006
834 Neimann et al
Page 6
2. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T.
Psoriasis is common, carries a substantial burden even when
not extensive, and is associated with widespread treatment
dissatisfaction. J Investig Dermatol Symp Proc 2004;9:136-9.
3. Neimann AL, Porter SB, Gelfand JM. Epidemiology of psoriasis.
Expert Rev Dermatol 2006;1:63-75.
4. Henseler T, Christophers E. Psoriasis of early and late onset:
characterization of two types of psoriasis vulgaris. J Am Acad
Dermatol 1985;13:450-6.
5. Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology,
clinical features, and quality of life. Ann Rheum Dis 2005;64
(Suppl 2):ii18-23; discussion ii24-5.
6. Smith AE, Kassab JY, Rowland Payne CM, Beer WE. Bimodality
in age of onset of psoriasis, in both patients and their relatives.
Dermatology 1993;186:181-6.
7. Gelfand JM, Feldman SR, Stern RS, Thomas J, Rolstad T, Margolis
DJ.Determinants of quality of lifein patientswith psoriasis: a study
from the US population. J Am Acad Dermatol 2004;51:704-8.
8. Javitz HS, Ward MM, Farber E, Nail L, Vallow SG. The direct cost
of care for psoriasis and psoriatic arthritis in the United States.
J Am Acad Dermatol 2002;46:850-60.
9. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM.
Psoriasis causes as much disability as other major medical
diseases. J Am Acad Dermatol 1999;41:401-7.
10. Krueger JG, Bowcock A. Psoriasis pathophysiology: current con-
cepts of pathogenesis. Ann Rheum Dis 2005;64(Suppl 2):ii30-6.
11. Schon MP, Boehncke WH. Psoriasis. N Engl J Med 2005;352:
1899-912.
12. Gaspari AA. Innate and adaptive immunity and the patho-
physiology of psoriasis. J Am Acad Dermatol 2006;54(Suppl):
S67-80.
13. Naldi L, Chatenoud L, Linder D, Belloni Fortina A, Peserico A,
Virgili AR, et al. Cigarette smoking, body mass index, and
stressful life events as risk factors for psoriasis: results from an
Italian case-control study. J Invest Dermatol 2005;125:61-7.
14. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H,
Kannel WB. Prediction of coronary heart disease using risk
factor categories. Circulation 1998;97:1837-47.
15. Ena P, Madeddu P, Glorioso N, Cerimele D, Rappelli A. High
prevalence of cardiovascular diseases and enhanced activity
of the renin-angiotensin system in psoriatic patients. Acta
Cardiol 1985;40:199-205.
16. Lindegard B. Mortality and causes of death among psoriatics.
Dermatologica 1989;179:91-2.
17. McDonald CJ. Cardiovascular disease in psoriasis. J Invest
Dermatol 1989;92:646-7.
18. McDonald CJ, Calabresi P. Thromboembolic disorders associ-
ated with psoriasis. Arch Dermatol 1973;107:918.
19. McDonald CJ, Calabresi P. Complication of psoriasis. JAMA
1973;224:629.
20. McDonald CJ, Calabresi P. Occlusive vascular disease in
psoriatic patients. N Engl J Med 1973;288:912.
21. Henseler T, Christophers E. Disease concomitance in psoriasis.
J Am Acad Dermatol 1995;32:982-6.
22. Lindegard B. Diseases associated with psoriasis in a general
population of 159,200 middle-aged, urban, native Swedes.
Dermatologica 1986;172:298-304.
23. Mallbris L, Granath F, Hamsten A, Stahle M. Psoriasis is
associated with lipid abnormalities at the onset of skin
disease. J Am Acad Dermatol 2006;54:614-21.
24. Hennekens CH, Buring JE. Epidemiology in medicine. Phila-
delphia: Lippincott Williams & Wilkins; 1987.
25. Gelfand JM, Dattani H, Margolis DJ. The UK General Practice
Research Database. In: Strom BL, editor. Pharmacoepidemiology.
New York: John Wiley and Sons; 2005. pp. 337-46.
26. Jick H, Jick SS, Derby LE. Validation of information recorded
on general practitioner based computerised data resource in
the United Kingdom. BMJ 1991;302:766-8.
27. Walley T, Mantgani A. The UK General Practice Research
Database. Lancet 1997;350:1097-9.
28. Gelfand JM, Wang X, Qing L, Neimann AL, Weinstein R,
Margolis DJ, et al. Epidemiology and treatment patterns of
psoriasis in the General Practice Research Database (GPRD).
Pharmacoepidemiol Drug Saf 2005;14(Suppl):S23.
29. Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ. Lymphoma
rates are low but increased in patients with psoriasis: results
from a population-based cohort study in the United Kingdom.
Arch Dermatol 2003;139:1425-9.
30. Lewis JD, Brensinger C. Agreement between GPRD smoking
data: a survey of general practitioners and a population-based
survey. Pharmacoepidemiol Drug Saf 2004;13:437-41.
31. Gelfand JM, Shin DB, Neimann AL, Wang X, Margolis DJ, Troxel AB.
The risk of lymphoma in patients with psoriasis. J Invest Dermatol
doi:10.1038/sj.jid.5700410. Published online June 1, 2006.
32. Nevitt GJ, Hutchinson PE. Psoriasis in the community: preva-
lence, severity and patients’ beliefs and attitudes towards the
disease. Br J Dermatol 1996;135:533-7.
33. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH,
Franklin BA, et al. Diagnosis and management of the metabolic
syndrome: an American Heart Association/National Heart, Lung,
and Blood Institute scientific statement. Curr Opin Cardiol
2006;21:1-6.
34. Wysocki J, Skoczynski S, Strozik A, Hochul B, Zygula M. [Meta-
bolic or immunometabolic syndrome?] Wiad Lek 2005;58:124-7.
Polish.
35. Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP.
Cytokine dysregulation, inflammation and well-being. Neuro-
immunomodulation 2005;12:255-69.
36. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM.
Reduced tyrosine kinase activity of the insulin receptor in
obesity-diabetes. Central role of tumor necrosis factor-alpha.
J Clin Invest 1994;94:1543-9.
37. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda
K, et al. A central role for JNK in obesity and insulin resistance.
Nature 2002;420:333-6.
38. McAllister-Sistilli CG, Caggiula AR, Knopf S, Rose CA, Miller AL,
Donny EC. The effects of nicotine on the immune system.
Psychoneuroendocrinology 1998;23:175-87.
39. Sopori M. Effects of cigarette smoke on the immune system.
Nat Rev Immunol 2002;2:372-7.
40. Aicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM,
Dimmeler S. Nicotine strongly activates dendritic cell-mediated
adaptive immunity: potential role for progression of athero-
sclerotic lesions. Circulation 2003;107:604-11.
41. Nouri-Shirazi M, Guinet E. Evidence for the immunosuppres-
sive role of nicotine on human dendritic cell functions.
Immunology 2003;109:365-73.
42. Sopori ML, Kozak W, Savage SM, Geng Y, Soszynski D,
Kluger MJ, et al. Effect of nicotine on the immune system:
possible regulation of immune responses by central and
peripheral mechanisms. Psychoneuroendocrinology 1998;23:
189-204.
43. Grando SA, Horton RM, Mauro TM, Kist DA, Lee TX, Dahl MV.
Activation of keratinocyte nicotinic cholinergic receptors
stimulates calcium influx and enhances cell differentiation.
J Invest Dermatol 1996;107:412-8.
44. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR,
et al. Impact of the metabolic syndrome on mortality from
coronary heart disease, cardiovascular disease, and all causes
in United States adults. Circulation 2004;110:1245-50.
JAM ACAD DERMATOL
VOLUME 55, NUMBER 5
Neimann et al 835
Page 7
  • Source
    • "Psoriasis is a common immune-mediated skin disease affecting 1.3–2.2 % of the UK population [1] with chronic plaque psoriasis being the most common (90 %) form [2]. The majority of patients have mild psoriasis although around 20–30 % of patients have more severe involvement that warrants consideration of systemic therapy [3]. Treatment options for severe psoriasis include systemic immunosuppressant therapies such as methotrexate and fumaric acid esters which are effective but associated with potential toxicities. "
    [Show abstract] [Hide abstract] ABSTRACT: Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease. This is a single centre, 39-week, prospective, randomised, open label, clinical trial of oral sitagliptin (Januvia ® ) in psoriasis patients who are due to undergo a course of narrow-band ultraviolet-B (NB-UVB) phototherapy. We plan to enrol 120 participants and allocate participants on a random and 1:1 basis to receive sitagliptin 100 mg daily for 24 weeks combined with NB-UVB or NB-UVB monotherapy. Participants will be followed up for 12 weeks after sitagliptin therapy is discontinued. The primary endpoint is the change in Psoriasis Area and Severity Index (PASI) 24 weeks after treatment initiation. Secondary endpoints include cumulative NB-UVB dose, number of NB-UVB treatments required to clear psoriasis, proportions of participants who achieve PASI-50 (50 % reduction in PASI from baseline), PASI-75, PASI-90 and the proportion of participants who relapse in each group. We will also analyse changes in cardiovascular disease risk factors, serum cytokine and hormone levels and peripheral blood mononuclear expression of immune proteins at 24 and 36 weeks. A subgroup of participants will have skin biopsies taken and analysed for skin levels and expression of immune cells, receptors, hormones and immune proteins. The genetic or epigenetic profile that predicts best response to DPP-4 inhibitor therapy will be analysed. The safety endpoints include the rate and severity of adverse events. This is the first randomised clinical trial assessing dipeptidyl peptidase-4 inhibition therapy in psoriasis. We hypothesise that sitagliptin therapy in combination with NB-UVB improves psoriasis severity compared to NB-UVB monotherapy. Trial registration ClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).
    Full-text · Article · Dec 2016 · Trials
  • Source
    • "Treg population with epidermal or dermal cell suspensions (Soler et al., 2013; Sugiyama et al., 239 2005). However, a recent study has found that many negative immune regulators, including Lande et al., 2014) and ADAMTSL5 (Arakawa et al., 2015), create the opportunity for Armstrong et al., 264 2013; Gelfand et al., 2006; Gisondi et al., 2007; Kremers et al., 2007; Neimann et al., 2006Krueger et al., 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Mild vs. severe psoriasis is often distinguished by clinical measures such as the extent of skin involvement or Psoriasis Area and Severity Index, both using arbitrary boundaries. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild vs. severe disease have not been performed. In this study, we used immunohistochemistry, RT-PCR, and gene arrays to phenotype North American patients with mild psoriasis (n=34; mean PASI 5.5) vs. severe psoriasis (n=23; mean PASI 23.2).
    Full-text · Article · May 2016 · Journal of Investigative Dermatology
  • Source
    • "More specifically, the incidence of inflammatory bowel disease is higher in patients with psoriasis than in the general population [18][19][20], and there is a suggested link between multiple sclerosis and psoriasis, as psoriasis is more common in those with multiple sclerosis than in control subjects [21]. Patients with psoriasis are more likely to be overweight, have diabetes, hypertension and dyslipidemia, and often have metabolic syndrome, with an associated increase in risk of cardiovascular morbidity and mortality [3, 18,[22][23][24][25][26][27]. Additionally, patients with psoriasis are at increased risk of stroke [28] and myocardial infarction [29]. "
    [Show abstract] [Hide abstract] ABSTRACT: Funding: Novartis, Italy.
    Preview · Article · Apr 2016
Show more