The relationship between duration of

psoriasis, vascular inflammation, and

cardiovascular events
a a b
Alexander Egeberg, MD, PhD, Lone Skov, MD, PhD, DMSc, Aditya A. Joshi, MD, Lotus
c d,e,f g
Mallbris, MD, PhD, Gunnar H. Gislason, MD, PhD, Jashin J. Wu, MD, Justin Rodante, PA-
b b
C, Joseph B. Lerman, MD,
b h b
Mark A. Ahlman, MD, Joel M. Gelfand, MD, MSCE, and Nehal N. Mehta, MD, MSCE
Hellerup and Copenhagen, Denmark; Bethesda, Maryland; Stockholm, Sweden;
Los Angeles, California; and Philadelphia, Pennsylvania

Background: Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a
major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular
inflammation and MACEs has not been well characterized.

Objectives: We utilized two resources to understand the effect of psoriasis duration

on vascular disease and CV events: (1) a human imaging study and (2) a population-
based study of CVD events.

From the Department of Dermatology and Allergya and Depart- safety and monitoring board), Dermira, Janssen Biologics,
ment of Cardiology, Herlev and Gentofte Hospital, University of Merck (data safety and monitoring board), Novartis Corp,
Copenhagen, Hellerupd; National Heart, Lung, and Blood Regeneron, Sanofi and Pfizer Inc; he receives research grants
Institute, National Institutes of Health, Bethesdab; Unit of
Dermatology and Venerology, Karolinska Institutet, Stockholmc;
Danish Heart Foundation, Copenhagene; National Institute of
Public Health, University of Southern Denmark, Copenhagenf;
Kaiser Permanente Los Angeles Medical Center, Los Angelesg;
and Department of Dermatology, Department of Biostatistics
and Epidemiology, and Center for Clinical Epidemiology and
Biostatistics, University of Pennsylvania, Philadelphia.h
The work at the National Institutes of Health cohort was
supported by the National Heart, Lung and Blood Institute
Intramural Research Program (HL006193-02). Dr Gelfand’s role
in this study was supported by National Institute of Arthritis
and Musculoskeletal and Skin Diseases grant K24-AR064310.
Disclosure: Dr Egeberg has received research funding from Pfizer
and Eli Lilly and honoraria as consultant and/or speaker from
Pfizer, Eli Lilly, Novartis, Galderma, and Janssen Pharmaceuti-
cals. Dr Skov has been a paid speaker for Pfizer, AbbVie, Eli Lilly,
Novartis, and LEO Pharma and has been a consultant or served
on advisory boards with Pfizer, AbbVie, Janssen Cilag, Novartis,
Eli Lilly, LEO Pharma, and Sanofi; she has served as an
investigator for Pfizer, AbbVie, Eli Lilly, Novartis, Amgen,
Regeneron, and LEO Pharma and received research and
educational grants from Pfizer, AbbVie, Novartis, Sanofi, Jans-
sen Cilag, and Leo Pharma. Dr Mallbris is currently employed by
Eli Lilly. Dr Gislason is supported by an unrestricted research
scholarship from the Novo Nordisk Foundation and reports
research grants from Pfizer, Bristol-Myers Squibb, AstraZeneca,
Bayer, and Boehringer Ingelheim. Dr Wu has received research
funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingel-
heim, Coherus Biosciences, Dermira, Eli Lilly, Janssen, Merck,
Novartis, Pfizer, Regeneron, Sandoz, and Sun Pharmaceutical
Industries; he is a consultant for AbbVie, Amgen, Celgene,
Dermira, Eli Lilly, Pfizer, Regeneron, and Sun Pharmaceutical
Industries. In the previous 12 months Dr Gelfand has served as
a consultant for and received honoraria from Coherus (data
 (to the Trustees of the University of Pennsylvania) from
Abbvie, Janssen, Novartis Corp, Regeneron, Sanofi,
Celgene, and Pfizer Inc; and he has received payment for
CME work related to psoriasis that was supported
indirectly by Lilly and Abbvie. Dr
Gelfand is a coepatent holder of resiquimod for treatment of
cutaneous T-cell lymphoma. Dr Mehta is a full-time US
gov- ernment employee and receives research grants to the
NHLBI from AbbVie, Janssen, Novartis and Celgene. No other
potential conflicts of interest were declared by the authors.
Dr Egeberg (Danish cohort) and Dr Mehta (National Institutes
of Health cohort) had full access to all of the data in the study
and take responsibility for integrity of the data and
accuracy of the data analysis. Drs Egeberg, Skov, Mallbris,
Gislason, Gelfand, and Mehta are responsible for the study
concept and design. Drs Joshi, Ahlman, Rodante,
Lerman, Gelfand, and Mehta (National Institutes of Health
cohort) and Drs Egeberg and Gislason (Danish cohort) are
responsible for acquisition, anal- ysis, and interpretation of
data. Drs Egeberg and Mehta are responsible for drafting
of the manuscript. All authors the are responsible for
critical revision of the manuscript for important intellectual
content. Drs Egeberg, Gislason and Joshi are responsible
for statistical analysis. Dr Mehta obtained funding. Drs
Egeberg, Skov, Gislason, and Mehta are responsible for
administrative, technical, or material support, and Drs Egeberg
and Mehta are responsible for study supervision.
Accepted for publication June 12, 2017.
Reprints not available from the authors.
Correspondence to: Alexander Egeberg, MD, PhD, Department of
Dermatology and Allergy, Herlev and Gentofte Hospital,
University of Copenhagen, Kildegsity of 28, Hellerup 2900,
Denmark. E-mail: alexander.egeberg@gmail.com; and Nehal N.
Mehta, MD, MSCE, Section of Inflammation and Cardiometabolic
Diseases, National Heart, Lung and Blood Institute, 10 Center Dr,
Bethesda, MD 20892. E-mail: nehal.mehta@nih.gov.
Published online August 18, 2017.
0190-9622/$36.00
© 2017 by the American Academy of Dermatology, Inc. Published
by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jaad.2017.06.028
 Methods: First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18
positron emission tomography/computed tomography (duration effect reported as
a b-coefficient). Second, MACE risk was examined by using nationwide registries
(adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general
population (n = 4,234,793).

Results: In the human imaging study, patients were young, of low CV risk by
traditional risk scores, and had a high prevalence of cardiometabolic diseases.
Vascular inflammation by fludeoxyglucose F 18 positron emission
tomography/computed tomography was significantly associated with disease
duration (b = 0.171, P = .002). In the population-based study, psoriasis duration had
strong relationship with MACE risk (1.0% per additional year of psoriasis duration
[hazard ratio, 1.010; 95% confidence interval, 1.007- 1.013]).

Limitations: These studies utilized observational data.

Conclusion: We found detrimental effects of psoriasis duration on vascular

inflammation and MACE, suggesting that cumulative duration of exposure to low-grade
chronic inflammation may accelerate vascular disease development and MACEs.
Providers should consider inquiring about duration of disease to counsel for heightened
CVD risk in psoriasis. ( J Am Acad Dermatol 2017;77:650-6.)

Key words: cardiovascular disease; 18-FDG PET/CT; inflammation; psoriasis.

Patients with psoriasis have an Thus, disease duration may represent a

increased inci- dence and prevalence of potentially easily obtainable measure of risk
CAPSULE SUMMARYfor CVD in inflammatory-based diseases.
car-
diovascular (CV) risk We investigated whether longer duration
1
factors and CV disease of pso- riasis would increase vascular
Patients with psoriasis have an increased
inflammation and a major adverse CV event
d

2-5
(CVD). Vascular incidence and prevalence of
inflammation by flu- (MACE)
cardiovascular risk factors and on account of the longer exposure
deoxyglucose F 18 (18- cardiovascular disease. to chronic, low-grade systemic
FDG) positron emission inflammation
We found a 1% increase in future
d observed in psoriasis.
cardiovascular event risk per additional
tomogra-
year of disease duration.
phy/computed MATERIALS
Health care providers should
d
considerAND METHODS
tomography (18-FDG Detailed
inquiring about duration of psoriasis descriptions of study
PET/CT), which is approvals, data sources, and methods are
when assessing cardiovascular risk.
prognostic for future 9
available online. Study approval for the
CV events, is increased interventional cohort study was obtained
in patients with from the National Heart, Lung, and Blood
6-8
psoriasis. Cumulative Institute (NHLBI) Institutional Review
exposure to Board in accordance with the Declaration
inflammation is linked of Helsinki. All Guidelines for Good
to increased Clinical Practice (GCP) and
atherosclerosis and CV
events, suggesting
that longer disease duration might
increase the risk for CVD and CV events.
those set forth by the National Institute
of Health
(NIH) Radiation Safety
Commission and in
the Belmont Report
(National Commission
for the Protection of
Human Subjects of
Biomedical and
Behavioral Research)
were followed. All
study partici- pants in
the NIH cohort pro-
vided written
informed consent.
Study approval was
obtained from the
Danish Data
Protection Agency
(ref. 2007-58-0015, int.
ref. GEH-
2014-018, I-Suite
02736).
Review of an ethics committee is not
required for register studies in Denmark.

Data sources
Data for the cohort study at the
National Heart, Lung, and Blood Institute
were obtained under the protocol titled
Psoriasis, Atherosclerosis, and
Cardiometabolic Disease Initiative
(NCT01778569). Complete and accurate
data (including medical con- ditions,
pharmacotherapy, treatment
interventions and surgical procedures,
income, and vital statistics) on the
Danish population are available from
nation- wide registers, which can be
linked at the individual level.

Study populations
NIH cohort. The longitudinal cohort
study group (referred to as the National
Institutes of Health [NIH] cohort)
comprised 190 consecutive
 Abbreviations used:
CV: cardiovascular
CVD: cardiovascular disease
CI: confidence interval
18-FDG: fludeoxyglucose F 18
18-FDG PET/CT: fludeoxyglucose F 18
positron
emission
tomography/
computed
tomography
HR: hazard ratio
MACE: major adverse
cardiovascular event
MI: myocardial infarction scanner, Siemens Healthcare, Malvern,
NIH: National Institutes of Health
PUVA: psoralen plus ultraviolet A PA). 18-FDG uptake within the aorta was
SD: standard deviation
TBR: target-to-background ratio measured by utilizing dedicated analysis
UVB: with psoriasis
patients ultraviolet
who B were recruited software for PET/CT (Extended Brilliance
from January 2013 through June 2016. A Workspace [Phillips Healthcare, Andover,
dermatologist or a certified physician MA]). One value of TBR was used as the
confirmed the onset and duration of primary outcome for each patient. The
psoriasis and assessed psoriasis severity association between vascular inflam-
using the Psoriasis Area Severity Index and mation and MACEs was not examined.
body surface area scores. Clinical Detailed description of TBR calculation is
8
parameters, including blood pressure, provided in our previous work.
height, weight, waist and hip Population cohort. The primary
outcome in
circumferences, were measured.
the population cohort was the first
Laboratory param- eters, including fasting
occurrence of a MACE (ie, a composite of
blood glucose, fasting lipid panel, white
myocardial infarction
blood count with differential, and systemic
inflammatory markers (including high-
sensitivity C-reactive protein and
erythrocyte sedi- mentation rate) were
evaluated in a clinical labora- tory. All
patients underwent 18-FDG PET/CT scans
for quantification of vascular
6-8
inflammation.
Total Danish population cohort. The total
Danish population cohort (henceforth
population cohort) comprised all Danish
citizens who were age 18 years or older,
alive, and residing in Denmark on January
1, 2008 (the study start).

Outcomes
NIH cohort. The primary outcome in the
NIH cohort was target-to-background
ratio (TBR) as- sessed by 18-FDG PET/CT
(Siemens Biograph mCT PET/CT 64-slice
Fig 1. Nelson-Aalen cumulative hazards graph the basis of average gross annual income
of the population cohort. Major adverse during the 5-year period before study
cardiovascular event risk in patients with inclusion.
psoriasis stratified on the basis of disease
duration less (n = 57,941) or more than 10
years (n = 29,220) compared with in the
general population (n = 4,234,793).

[MI], ischemic stroke, and CV death,

respectively). Secondary outcomes
included specific occur- rences of MI,
ischemic stroke, and death due to CV.

Covariates
NIH cohort. Baseline treatment for the
NIH cohort was defined for any of the
following thera- pies: systemic
nonbiologic agents (henceforth sys-
temic) or biologic therapy (systemic
steroids, methotrexate, adalimumab,
etanercept, and usteki- numab), statins,
psoralen plus ultraviolet A (PUVA) or
ultraviolet B (UVB), and topical
treatments. Patients completed survey-
based questionnaires regarding
smoking, previous CVD, family history of
CVD, and previous established
diagnoses of hyper- tension and
diabetes. Patient responses were then
ascertained by interview with the
physician. All parameters were assessed
up to 12 months before study inclusion.
Population cohort. Baseline treatment
up to 6 months before study inclusion
was defined for the following therapies:
biologics (adalimumab, efalizumab,
etanercept, infliximab, and ustekinu-
mab), cholesterol-lowering drugs,
cyclosporine, methotrexate, PUVA/UVB,
retinoids (acitretin/etreti- nate), and
topical vitamin D analogues. Baseline
comorbidity was assessed up to 5 years
before study inclusion for the following
conditions: alcohol abuse, smoking,
CVD, diabetes, hypertension, and
psoriatic arthritis. We calculated age-
standardized socioeconomic status on
Table I. Baseline characteristics of the total population cohort
Reference population Psoriasis
Characteristic (n = 4,234,793) (n = 87,161)
Age, mean (SD), y 48.6 (18.0) 53.8 (16.3)
Sex, n (%)
Women 2,148,653 (50.7) 45,809 (52.6)
Men 2,086,140 (49.3) 41,352 (47.4)
Duration of psoriasis, y
Mean (SD) NA 7.8 (5.2)
Median (IQR) NA 7.7 (3.9-11.2)
Age at onset of psoriasis, mean (SD), y NA 46.0 (16.6)
Socioeconomic status, mean (SD) 2.0 (1.3) 2.2 (1.3)
Hospitalized (inpatient) for psoriasis, n (%) NA 4975 (5.7)
Smoking, n (%) 337,551 (8.0) 10,459 (12.0)
Comorbidity, n (%)
Alcohol abuse 58,671 (1.4) 1672 (1.9)
Cardiovascular disease 364,023 (8.6) 11,737 (13.5)
Diabetes 151,043 (3.6) 5376 (6.2)
Hypertension 506,836 (12.0) 15,908 (18.3)
Psoriatic arthritis 2515 (0.1) 5742 (6.6)
Treatment, n (%)*
Biologics 2760 (0.1) 663 (0.8)
Cholesterol-lowering drugs 384,425 (9.1) 12,436 (14.3)
Cyclosporine 985 (0.0) 193 (0.2)
Methotrexate 13,971 (0.3) 3189 (3.7)
PUVA/UVB phototherapy 346 (0.0) 264 (0.3)
Retinoids (acitretin/etretinate) 395 (0.0) 553 (0.6)
Topical vitamin D analogues NA 12,621 (14.5)

IQR, Interquartile range; NA, not applicable; PUVA, psoralen plus ultraviolet A; SD, standard deviation; UVB, ultraviolet B.
*Within the last 6 months.

Statistical analysis comparisons were done using Pearson’s

Results were presented with 95% chi-square test.
confidence intervals (CIs) where applicable, NIH cohort. Unadjusted regression
and P values less than 0.05 were analyses were performed to evaluate for
considered statistically significant. potential relation- ships between
Statistical analyses were performed with cardiometabolic variables and psori- asis
STATA software (versions 12.0 and 13.0, duration. We conducted multivariable
StataCorp, College Station, TX) and SAS linear regression analyses to evaluate the
software (version 9.4, SAS Institute, Inc, associations of vascular inflammation (TBR)
Cary, NC). with psoriasis duration.
Summary statistics were presented as
means with the standard deviation (SD) for
normally distributed variables, medians,
and interquartile range for non- normally
distributed continuous variables and fre-
quencies for categorical variables.
Normality was assessed by skewness and
kurtosis. Parametric variables were
compared between groups using the
Student t test and the Mann-Whitney U
test was performed for nonparametric
variables. Dichotomous variable
These analyses were adjusted for age at
onset of psoriasis, sex, and traditional
CV risk assessed by Framingham risk
score, history of CVD, diabetes,
hypertension, treatment with statins,
smoking, and alcohol abuse. We
assessed the F statistics along with P
values as well as the root mean squared
error values to assess for the goodness
of fit for every model.
Population cohort. Incidence rates were
sum- marized per 1000 person-years,
and Cox regression was performed to
estimate hazard ratios (HRs).
Multivariable models were adjusted for
age, sex, socioeconomic status,
previous CVD, smoking, alcohol abuse,
diabetes, hypertension, and use of
statins. We performed separate
sensitivity analyses, from which patients
with psoriatic arthritis and those with
previous CVD, respectively, were
excluded. We performed additional
analyses in which psoriasis was defined
by using only hospital diagnoses.
Moreover, we did analyses in which the
population cohort was divided into
older (born before 1960) and younger
(born in or after 1960) individuals,
respectively. Lastly, we repeated our
analyses with adjustment for age at
onset of psoriasis.
Table II. Univariable and multivariable hazard ratios of MACEs in patients with psoriasis compared with in the
general population
Univariable Multivariable
Characteristic Hazard ratio 95% CI P value Hazard ratio 95% CI P value
Duration of psoriasis 1.039 1.036-1.042 \.0001 1.010 1.007-1.013 \.0001
Age 1.087 1.087-1.087 \.0001 1.075 1.075-1.076 \.0001
Male sex 1.230 1.218-1.242 \.0001 1.516 1.501-1.532 \.0001
Socioeconomic status
0 (lowest) 1.722 1.695-1.748 \.0001 1.118 1.101-1.136 \.0001
1 (below average) 2.355 2.321-2.389 \.0001 1.113 1.096-1.130 \.0001
2 (average) (reference) (reference)
3 (above average) 0.536 0.526-0.547 \.0001 0.855 0.838-0.873 \.0001
4 (highest) 0.478 0.468-0.488 \.0001 0.744 0.729-0.760 \.0001
Previous CVD 8.667 8.581-8.755 \.0001 2.278 2.252-2.305 \.0001
Statin use 3.594 3.556-3.631 \.0001 0.908 0.897-0.919 \.0001
Diabetes 3.743 3.692-3.795 \.0001 1.420 1.399-1.441 \.0001
Hypertension 5.721 5.665-5.778 \.0001 1.394 1.379-1.411 \.0001
Alcohol abuse 1.612 1.565-1.659 \.0001 1.905 1.850-1.961 \.0001
Smoking 2.654 2.620-2.689 \.0001 1.697 1.676-1.720 \.0001

CVD, Cardiovascular disease; CI, confidence interval.

Fig 2. Association between vascular inflammation and psoriasis disease

duration in the National Institutes of Health cohort. Unadjusted and fully
adjusted regression plots demonstrate a direct association between psoriasis
disease duration and vascular inflammation in the National Institutes of
Health cohort beyond traditional cardiovascular risk factors.

RESULTS middle-aged men (57% men), overweight,

NIH cohort with mild insulin resistance (median
The NIH cohort comprised 190 patients insulin resistance of
with mild- to-moderate psoriasis
(Supplemental Table I; avail- able at
http://www.jaad.org), who were primarily
2.77), but at low CV risk by Framingham
risk score. Vascular inflammation
assessed by TBR (mean 6 SD = 1.70 6
0.26) demonstrated increased vascular
10
inflammation. Strong associations with
vascular inflammation were seen for male
sex, smoking, Framingham 10-year risk,
and body mass index (BMI). The per-year
incremental effect of psoriasis

duration on vascular inflammation
(assessed by TBR) showed that duration of
psoriasis was associated with increased
vascular inflammation (b = 0.086, P =
.040), a relationship that persisted beyond
adjustment for traditional CV risk factors
(b = 0.171, P = .002) (Fig 1 and
Supplemental Tables II and III; available at
http://www.jaad.org).
Population cohort
The population cohort comprised
4,321,954 in- dividuals, including 87,161
patients with psoriasis (maximum
disease duration was 31.1 years) (Table
I). During a mean (6SD) follow-up of 4.7
(0.9) years, MACEs were experienced by
a total of 152,122 patients in the general
population (inci- dence rate/1,000
person-years, 7.56 [95% CI, 7.52- 7.60])
and 4472 patients with psoriasis
(incidence rate/1,000 person-years,
10.94; [95% CI, 10.62-
11.26]), respectively.
In unadjusted analyses, psoriasis was
associated with 3.9% increased risk for
MACEs per additional year of disease
duration, and in multivariable anal- ysis,
the risk of MACEs increased by 1.0% per
additional year of psoriasis duration (HR,
1.010; 95% CI, 1.007-1.013) (Table II and
Fig 2). For
secondary end points, the multivariable
HRs associ- ated with duration of psoriasis
were 1.006 (95% CI, 1.001-1.012) for MI,
1.011 (95% CI, 1.007-1.016) for
ischemic stroke, and 1.011 (95% CI, 1.007-
1.015) for CV death, respectively.
on CVD beyond traditional CV risk factors,
even in patients with low CV risk scores.
Notably, every 1 SD increase in duration of
psoriasis increases the TBR by 2.5%, which
roughly translates into an absolute
increase of 10% in future adverse events on
the basis of a recent large population
11
study.
As in the case of studies of rheumatoid
12
arthritis, most but not all studies have
associated psoriasis with an increased risk
2-5,13-15
for CVD, yet data suggest that classic
CV risk factors alone do not fully capture this
heightened risk, and systemic inflam-
mation has been put forward as a potential
expla- nation for the link between psoriasis
and CVD. Along this line, inflammation is
associated with impaired insulin sensitivity,
carotid intima-media thickening,
endothelial dysfunction, aortic stiffness,
vascular inflammation, and coronary plaque
burden, with such CVD markers occurring
more frequently in

DISCUSSION
We utilized a human imaging study
and a population-based study to
investigate whether the duration of
psoriasis increases the risk for CVD and
MACEs, and we have presented novel and
convincing evidence to suggest a
detrimental effect of psoriasis duration
 concurrent medica- tion, and
16-18
patients with psoriasis. These insults socioeconomic status. Observational
could occur because of consistent data alone from a single study are not
vascular damage consequent to sufficient to establish causality. However,
immune activation in those with longer comparable findings across different
duration of disease. populations, which were obtained by
We opted for a translational using our approach of both
epidemiologic approach, utilizing a observational and vascular imaging data,
human imaging study com- bined with add strength and credibility to our
observational registry data to findings, and the results are consistent
emphasize the putative clinical with prior work demonstrating that
relevance of increased vascular duration of psoriasis is an independent
inflammation observed in our study. risk factor for MI and coronary artery
21,22
Specifically, we found a 1% increase in disease measured by angiography.
future CV event risk per additional year In conclusion, we have provided strong
of disease duration, which is an effect size novel evidence that duration of psoriasis
similar to that of smoking. Each of the increases vascular inflammation and the
compo- nents of the composite risk of MACEs. Providers should consider
outcome of MACEs also increased with inquiring about duration of psoriasis when
longer duration of disease, suggesting assessing CV risk stratification.
that duration of inflammation increases
REFERENCES
all vascular diseaseerelated events. 1. Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB,
Nevertheless, we emphasize that the Gelfand JM. Prevalence of cardiovascular risk factors in
patients with psoriasis. J Am Acad Dermatol. 2006;55:829-835.
independent association between
2. Gelfand JM, Azfar RS, Mehta NN. Psoriasis and cardiovascular
psoriasis and CVD remains a topic of risk: strength in numbers. J Invest Dermatol. 2010;130:919-922.
19
ongoing debate, as does the effect of
systemic therapy on the vascular
20
inflammation and CV events.
A limitation in the population cohort
was a lack of information for BMI and
levels of physical exercise. However,
such data were available in the NIH
cohort, and adjustment for BMI did not
significantly change the relationship
between duration of disease and
vascular inflammation. Furthermore,
previous CVD and diabetes, which are
two major predictors of MACEs in the
population cohort, did not relate to
vascular inflammation in the NIH
cohort. This is likely due to the low
number of patients with these
characteristics in the NIH cohort.
Important strengths include the sheer
number of participants and the high
accuracy of the nationwide registries,
which minimized bias due to sex, age,
 3. Gelfand JM, Mehta NN, Langan SM. Psoriasis and cardiovas-
cular risk: strength in numbers, part II. J Invest Dermatol. 2011;
131:1007-1010.
4. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ,
Troxel AB. Risk of myocardial infarction in patients with
psoriasis. JAMA. 2006;296:1735-1741.
5. Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB,
Gelfand JM. Patients with severe psoriasis are at increased
risk of cardiovascular mortality: cohort study using the
General Practice Research Database. Eur Heart J. 2010;31:
1000-1006.
6. Mehta NN, Yu Y, Saboury B, et al. Systemic and vascular
inflammation in patients with moderate to severe psoriasis as
measured by [18F]-fluorodeoxyglucose positron emission
tomography-computed tomography (FDG-PET/CT): a pilot
study. Arch Dermatol. 2011;147:1031-1039.
7. Mehta NN, Torigian DA, Gelfand JM, Saboury B, Alavi A.
Quantification of atherosclerotic plaque activity and vascular
inflammation using [18-F] fluorodeoxyglucose positron emis-
sion tomography/computed tomography (FDG-PET/CT). J Vis
Exp. 2012:e3777.
8. Naik HB, Natarajan B, Stansky E, et al. Severity of psoriasis
associates with aortic vascular inflammation detected by FDG
PET/CT and neutrophil activation in a prospective observa-
tional study. Arterioscler Thromb Vasc Biol. 2015;35:2667-2676.
9. Egeberg, Alexander (2017). ‘‘JAAD-D-17-00307 Supplementary
Materials’’, Mendeley Data, v2. http://dx.doi.org/10.17632/
t7syfrg4yr.2.
10. Fayad ZA, Mani V, Woodward M, et al. Safety and efficacy of
dalcetrapib on atherosclerotic disease using novel non-
invasive multimodality imaging (dal-PLAQUE): a rando-
mised clinical trial. Lancet. 2011;378:1547-1559.
11. Figueroa AL, Abdelbaky A, Truong QA, et al. Measurement of
arterial activity on routine FDG PET/CT images improves
prediction of risk of future CV events. JACC Cardiovasc
Imaging. 2013;6:1250-1259.
12. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ,
Lacaille D. Risk of incident cardiovascular events in patients
with rheumatoid arthritis: a meta-analysis of observational
studies. Ann Rheum Dis. 2012;71:1524-1529.
13. Egeberg A, Thyssen JP, Jensen P, Gislason GH, Skov L. Risk of
myocardial infarction in patients with psoriasis and psoriatic
arthritis: a nationwide cohort study. Acta Derm Venereol. 2017;97:
819-824.
14. Parisi R, Rutter MK, Lunt M, et al. Psoriasis and the risk of
major cardiovascular events: cohort study using the Clinical
Practice Research Datalink. J Invest Dermatol. 2015;135:
2189-2197.
15. Dowlatshahi EA, Kavousi M, Nijsten T, et al. Psoriasis is not
associated with atherosclerosis and incident cardiovascular
events: the Rotterdam Study. J Invest Dermatol. 2013;133:
2347-2354.
16. Boehncke WH, Boehncke S, Tobin AM, Kirby B. The
’psoriatic march’: a concept of how severe psoriasis may
drive cardiovascular comorbidity. Exper Dermatol. 2011;20:
303-307.
17. Balci DD, Balci A, Karazincir S, et al. Increased carotid artery
intima-media thickness and impaired endothelial function in
psoriasis. J Eur Acad Dermatol Venereol. 2009;23:1-6.
18. Gyldenlove M, Storgaard H, Holst JJ, Vilsboll T, Knop FK,
Skov L. Patients with psoriasis are insulin resistant. J Am Acad
Dermatol. 2015;72:599-605.
19. Ogdie A, Troxel AB, Mehta NN, Gelfand JM. Psoriasis and
cardiovascular risk: strength in numbers. Part 3. J Invest
Dermatol. 2015;135:2148-2150.
20. Bissonnette R, Harel F, Krueger JG, et al. TNF-alpha antagonist
and vascular inflammation in patients with psoriasis vulgaris: a
randomized placebo-controlled study. J Invest Dermatol. 2017;
137:1638-1645.
21. Li WQ, Han JL, Manson JE, et al. Psoriasis and risk of nonfatal
cardiovascular disease in U.S. women: a cohort study. Br J
Dermatol. 2012;166:811-818.
22. Armstrong AW, Harskamp CT, Ledo L, Rogers JH,
Armstrong EJ. Coronary artery disease in patients with psori-
asis referred for coronary angiography. Am J Cardiol. 2012;109:
976-980.
Supplemental Table I. Demographic and
clinical characteristics of the NIH cohort (N = 190)
Parameter Value
Demographic and clinical history
Median age, y 50 6 12.6
Age at onset, y 29.4 6 15.7
Males, n (%) 109 (57%)
Hypertension, n (%) 54 (28%)
Type 2 diabetes, n (%) 19 (10%)
Hyperlipidemia, n (%) 89 (47%)
Current smoker, n (%) 19 (10%)
Metabolic syndrome, n (%) 48 (25%)
Statin use, n (%) 63 (33%)
Clinical and laboratory parameters
Body mass index, kg/m2 29.5 6 6
Systolic blood pressure, mm Hg 122.7 6 14.9
Diastolic blood pressure, mm Hg 72.2 6 10
Total cholesterol level, mg/dL 181.9 6 36.7
Low-density lipoprotein cholesterol 102.0 6 30.4
level, mg/dL
High-density lipoprotein cholesterol 55.6 6 17.5
level, mg/dL
Median triglyceride level (IQR), mg/dL 101 (76-137)
Median Hs-CRP level (IQR), mg/L 2.0 (0.8-4.2)
Median Framingham risk score (IQR) 3 (1-6)
Glucose level, mg/dL 101 6 19.5
Median insulin level (IQR), mIU/L 11.1 (7.1-17.7)
Median HOMA-IR (IQR) 2.77 (1.65-4.49)
Psoriasis characteristics
Median disease duration (IQR), y 20 (9-30)
Median body surface area % affected 4.3 (2.4-13.3)
(IQR)
Median Psoriasis Area Severity Index 5.7 (2.9-10.1)
score (IQR)
Systemic/biologic therapy, N (%) 72 (38%)
Aortic vascular inflammation
Target-to-background ratio 1.70 6 0.26

All values reported as mean 6 SD or median (interquartile range)

for continuous variables and as n (%) for categorical variables.
P values represent comparison between groups by disease
duration and were calculated by the Student t test or Mann-
Whitney U test for continuous variables and by Pearson’s chi-
square test for categorical variables.
Hs-CRP, High-sensitivity C-reactive protein; HOMA-IR, homeostatic
model assessment of insulin resistance; IQR, interquartile range;
NIH, National Institutes of Health; SD, standard deviation.
Supplemental Table II. Univariable regression
analyses between target-to-background ratio and
study variables in the NIH cohort
Target-to-background
Parameter ratio
Demographic and clinical history
Age at onset 0.172 (.02)
Males 0.266 (\.001)
Hypertension 0.165 (\.001)
Type 2 diabetes 0.014 (.734)
Hyperlipidemia 0.257 (\.001)
Current smoking 0.133 (.002)
Metabolic syndrome 0.344 (\.001)
Waist-to-hip ratio 0.047 (.293)
Tobacco use 0.169 (\.001)
Alcohol abuse 0.014 (.734)
Statin use 0.145 (.001)
Previous CVD 0.075 (.077)
Clinical and laboratory parameters
BMI 0.545 (\.001)
SBP 0.220 (\.001)
DBP 0.111 (.008)
Total cholesterol level 0.072 (.086)
LDL level 0.106 (.012)
HDL level —0.373 (\.001)
Triglyceride level 0.201 (\.001)
FRS 0.406 (\.001)
Glucose level 0.076 (.071)
Insulin level 0.230 (.001)
HOMA-IR 0.282 (.001)
Hs-CRP level 0.142 (.061)
Psoriasis characteristics
PASI score 0.156 (\.001)
BSA 0.075 (.305)
Systemic and/or biologic therapy 0.009 (.903)

All values are represented as b value (P value).

BMI, Body mass index; BSA, body surface area; CVD, cardiovascular
disease; DBP, diastolic blood pressure; FRS, Framingham risk score;
HDL, high-density lipoprotein; HOMA-IR, homeostatic model
assessment of insulin resistance; Hs-CRP, high-sensitivity C-
reactive protein; LDL, low-density lipoprotein; NIH, National
Institutes of Health; PASI, Psoriasis Area Severity Index; SBP,
systolic blood pressure.
Supplemental Table III. Univariable and multivariable regression analyses of vascular inflammation versus
disease duration in the NIH cohort
Vascular inflammation (N = 190)
Univariable Multivariable
Parameter b (P value) 95% CI b (P value) 95% CI
Duration of psoriasis 0.086 (.040) 0.040-0.132 0.171 (.002) 0.112-0.230
Age at onset 0.172 (.020) —0.163 to 0.507 0.147 (.010) —0.331 to 0.625
Male sex 0.266 (\.001) 0.221-0.311 0.206 (\.001) 0.161-0.251
Previous CVD 0.075 (.077) 0.026-0.124 0.042 (.325) —0.007 to 0.091
Statin use 0.145 (.001) 0.099-0.191 0.122 (.027) 0.062-0.182
Diabetes 0.014 (.735) —0.033 to 0.061 0.044 (.295) —0.002 to 0.090
Hypertension 0.165 (\.001) 0.120-0.210 0.07 (.085) 0.050-0.090
Alcohol abuse 0.014 (.734) —0.032 to 0.060 0.049 (.229) 0.005-0.093
Smoking 0.133 (.002) 0.087-0.179 0.187 (\.001) 0.142-0.232
Framingham risk score 0.406 (\.001) 0.226-0.586 0.337 (\.001) 0.082-0.592

All values are reported as standardized b (P value). 95% CI values represent the CI for standardized b-values.
NIH, National Institutes of Health; CI, confidence interval; CVD, cardiovascular disease.
 Translated

Hubungan antara durasi psoriasis, imflamasi vaskuler, dan

kejadian kardiovaskuler

Latar Belakang: Psoriasis dihubungkan dengan resiko penyakit kardiovaskuler (PKV) dan
kejadian mayor kardiovaskuler yang berat (KMKB). Apakah durasi psorias mempengaruhi resiko
inflamasi vaskuler dan KMKB masih belum terincikan.

Objektif: Kami menggunakan dua sumber untuk memahami efek durasi psoriasis terhadap penyakit
vaskuler dan kejadian KV: (1) studi pencitraan manusia dan (2) studi kejadian PKV berbasis
populasi.

Metode: Pertama, pasien dengan psoriasis (N=190) menjalani 18-FDG PET/CT. Kedua, resiko
KMKB dipantau dengan menggunakan registri tingkat nasional (rasio pasien dengan psoriasis
(n=87,161) versus populasi umum (n=4,234,793)).

Hasil: Pada studi pencitraan manusia, pasiennya muda, dengan resiko rendah PKV menggunakan
skor resiko tradisional, dan memiliki prevalensi tinggi penyakit kardiometabolik. Inflamasi vaskuler
oleh 18-FDG PET/CT sangat signifikan dihubungkan dengan durasi penyakit (B = 0.171, P = .002).
Pada studi berbasis populasi, durasi psoriasis memiliki hubungan erat dengan resiko KMKB (1.0%
per tambahan tahun durasi psoriasis[hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]).

Hambatan: Studi ini menggunakan data observasional.

Kesimpulan: Kami menemukan efek merugikan dari durasis psoriasis pada inflamasi vaskuler dan
KMKB, yang mengindikasikan bahwa durasi terakumulasi dari inflamasi kronis kelas-rendah
mungkin mempercepat perkembangan penyakit vaskuler dan KMKB. Para penyedia layanan harus
mempertimbangkan menanyakan durasi penyakit untuk memberikan informasi mengenai
peningkatan resiko PKV pada pasien dengan psoriasis.

Kata kunci: Penyakit kardiovaskuler; 18-FDG PET/CT; inflamasi; psoriasis.

 Pasien dengan psoriasis memiliki peningkatan kejadian dan prevalensi untuk faktor resiko
kardiovaskuler (KV) dan penyakit KV (PKV). Inflamasi vaskuler oleh fludeoxyglucose F 18 (18-
FDG) postiron emission tomography/computed tomography (18-FDG PET/CT), yang bersifat
prognostik untuk kejadian KV di masa depan, meningkat pada pasien dengan psoriasis. Paparan
kumulatif terhadap inflamasi dihubungkan dengan peningkatan aterosklerosis dan kejadian KV,
yang memberi kesan bahwa penyakit dengan durasi lebih lama mungkin dapat meningkatkan resiko
untuk PKV dan kejadian KV. Karena itu, durasi penyakit mungkin dapat mewakili ukuran resiko
yang berpotensi mudah untuk didapat untuk PKV pada penyakit berbasis inflamasi.
Kami menyelidiki apakah psoriasis dengan durasi lebih lama dapat meningkatan inflamasi
vaskuler dan kejadian mayor kardiovaskuler yang berat (KMKB) karena lebih lama terpapar
inflamasi sistemik kronis kelas-rendah yang terlihat pada psoriasis.

BAHAN DAN METODE

Deskripsi rinci untuk persetujuan studi, sumber data, dan metode tersedia secara online.
Persetujuan studi untuk studi kohort intervensi diperoleh dari kelembagaan NHLBI yang sesuai
dengan Deklarasi Helinski. Seluruh pedoman untuk praktek klinis yang baik (PKB) dan yang
ditetapkan oleh NIH bagian Komisi Keselamatan Radiasi dan pada Laporan Belmont juga diikuti.
Seluruh peserta studi memberikan informed consent tertulis. Persetujuan studi diperoleh dari Agensi
Perlindungan Data Danish. Ulasan dari komite etika tidak diperlukan untuk mendaftarkan studi di
Denmark.
Sumber data
Data untuk studi kohort di NHLBI didapatkan dibawah protokol berjudul Psoriasis,
Aterosklerosis, dan Inisiatif Penyakit Kardiometabolik. Data lengkap dan akurat (termasuk kondisi
medis, farmakoterapi, intervensi pengobatan dan prosedur pembedahan, pendapatan, statistik vital)
pada populasi Danish yang tersedia di registri nasional, yang dapat dihubungkan pada level
individual.

Populasi studi
Kohort NIH. Grup studi kohort longitudinal (disebut juga korhort NIH) terdiri dari 190
pasien konsekutif dengan psoriasis yang direkrut dari Januari 2013 sampai Juni 2016. Dermatologis
atau dokter berlisensi mengkonfirmasi onset dan durasi psoriasis dan menegakkan keparahan
psoriasis menggunakan Indeks Keparahan Area Psoriasis dan skor area permukaan tubuh. Parameter
klinis yang diukur termasuk tekanan darah, tinggi badan, berat badan, rasio lingkar perut dan lingkar
pinggang.Parameter lab, termasuk gula darah puasa, kadar lipid puasa, hitung jenis leukosit, dan
penanda inflamasi sistermik (termasuk CRP dan rasio sedimentasi eritrosit) juga dievaluasi di lab
klinis. Semua pasien menjalani 18-FDG PET/CT scan untuk kuantifikasi inflamasi vaskuler.
Total kohort populasi Danish. Total kohort populasi Danish (kohort populasi) terdiri dari
seluruh penduduk Danish berumur 18 tahun atau lebih, hidup, dan tinggal di Denmark pada 1
Januari 2008 (permulaan studi).

Hasil
Kohort NIH. Hasil primer pada kohort NIH adalah rasio target-ke-latar belakang (RTLB)
yang dinilai oleh 18-FDG PET/CT. Serapan 18-FDG pada aorta diukur dengan mengutilisasi
perangkat lunak analisis terdedikasi untuk PET/CT. Satu nilai RTLB digunakan sebagai hasil primer
untuk setiap pasien. Asosiasi antara inflamasi vaskuler dan KMKB tidak diperiksa. Deskripsi terinci
kalkulasi RTLB sudah dikemukakan di pekerjaan kami sebelumnya.
Kohort populasi. Hasil primer pada kohort populasi merupakan kejadian pertama dari
KMKB (contoh, gabungan dari infark miokard, stroke iskemik, meninggal akibat kejadian KV).
Hasil sekunder termasuk kejadian spesifik infark miokard, stroke iskemik, dan menginggal karena
kejadian KV.

Kovariat
Kohort NIH. Pengobatan dasar untuk kohort NIH didefinisikan sebagai salah satu dari
terapi berikut ini: agen sistemik non-biologik (sistemik) atau terapi biologik (steroid sistemik,
metotreksat, adalimumab, etanercept, dan ustekinumab), golongan statin, PUVA/UVB, dan
pengobatan topikal. Para pasien menyelesaikan kuisoner berbasis survey yang menyangkut
kebiasaan merokok, PKV sebelumnya, riwayat keluarga dengan PKV, dan diagnosa mapan
sebelumnya untuk hipertensi dan diabetes. Respon pasien lalu dipastikan dengan wawancara dengan
dokternya. Seluruh parameter ditetapkan hingga 12 bulan sebelum studi inklusi.
Kohort populasi. Pengobatan dasar hingga 6 bulan sebelum studi inklusi didefinisikan
sebagai salah satu dari terapi berikut ini: terapi biologik (adalimumab, efalizumab, etanercept,
infliximab, dan ustekinumab), obat penurun kolestrol, siklosporin, metotreksat, PUVA/UVB,
golongan retinoid, dan analog topikal vitamin D. Komorbiditas dasar ditetapkan hingga 5 tahun
sebelum studi inklusi untuk kondisi berikut ini: penyalahgunaan alkohol, merokok, PKV, diabetes,
hipertensi, dan psoriasis artritis. Kami mengkalkulasi status sosioekonomi berstandar usia dengan
basis pendapatan tahunan bruto rata-rata pada periode 5 tahun sebelum studi inklusi.

Analisis statistikal
Hasil dipresentasikan dengan 95% Confidence Interval (CIs) yang dapat diaplikasikan, dan
P value dibawah 0.05 dianggap signifikan secara statistikal. Analisis statistikal dilakukan
menggunakan perangkat lunak STATA dan SAS.
Ringkasan statistik yang disajikan sebagai sarana dengan standar deviasi (SD) untuk variabel
yang didistribusikan secara normal, median, dan rentang interquartil untuk variabel yang biasanya
tidak didistribusikan secara normal dan frekuensi untuk variabel berkategori. Kenormalan dinilai
oleh skewness dan kurtosis. Variabel parameter dibandingkan antar grup menggunakan tes Student t
dan tes Mann-Whitney U untuk variabel non-parameter. Perbandingan variabel Dichotomous
dilakukan menggunakan tes Pearson’s chi-square.
Kohort NIH. Analisis regresi tak disesuaikan dilakukan untuk mengevaluasi potensi
hubungan antara variabel kardiometabolik dan durasi psoriasis. Kami melakukan analisis regresi
linear multivariabel untuk mengevaluasi hubungan inflamasi vaskuler dengan durasi psoriasis.
Analisis ini disesuaikan untuk usia onset psoriasis, jenis kelamin, dan resiko KV tradisional
ditetapkan menggunakan nilai resiko Framingham, riwayat PKV, diabetes, hipertensi, pengobatan
dengan statin, merokok, dan penyalahgunaan alkohol. Kami menilai statistik F bersama dengan P
value serta the root mean squared error value untuk menetapkan kecocokan untuk setiap model.
Kohort populasi. Tingkat kejadian diringkas per 1000 orang-tahun, dan regresi Cox
dilakukan untuk menilai Hazard ratios (HR). Model multivariabel disesuaikan untuk usia, jenis
kelamin, status sosioekonomi, PKV sebelumnya, merokok, penyalahgunaan alkohol, diabetes,
hipertensi, dan penggunaan obat golongan statin. Kami melakukan analisis sensitif terpisah, dimana
pasien dengan psoriasis artritis dan yang dengan PKV sebelumnya, masing-masing, disingkirkan.
Kami melakukan analisis tambahan dimana psoriasis hanya didefinisikan dari yang sudah
terdiagnosa di rumah sakit. Lebih lagi, kami melakukan analisis dimana kohort populasi dibagi,
masing-masing menjadi individu yang lebih tua (lahir sebelum 1960) dan yang lebih muda (lahir
setelah 1960). Terakhir, kami mengulangi analisis kami dengan penyesuaian untuk usia saat onset
psoriasis.
HASIL
Kohort NIH
Kohort NIH terdiri dari 190 pasien dengan psoriasis kelas rendah-ke-sedang, terutama pria
paruh baya (57% pria), berat badan berlebih, dengan resistensi insulin ringan (median resisten
insulin 2.77), namun dengan resiko KV rendah berdasarkan nilai resiko Framingham. Inflamasi
vaskuler yang dinilai oleh RTLB (mean +- SD = 1.70 +- 0.26) menunjukkan adanya peningkatan
inflamasi vaskuler. Terlihat hubungan kuat antara inflamasi vaskuler dengan jenis kelamin laki-laki,
merokok, resiko 10-tahun Framingham, dan indeks massa tubuh (IMT). Efek tambahan per tahun
dari durasi psoriasis pada inflamasi vaskuler menunjukkan adanya hubungan durasi psoriasis
dengan peningkatan inflamasi vaskuler (B = 0.086, P = .040), hubungan yang bertahan diluar
penyesuaian untuk faktor resiko KV tradisional (B = 0.171, P = .002).

Kohort populasi
Kohort populasi terdiri dari 4,321,954 individu, termasuk 87,161 pasien dengan psoriasis
(durasi maksimum penyakit 31.1 tahun). Saat follow-up rerata (+-SD) pada 4.7 tahun, KMKB
dialami oleh 152,122 pasien pada populasi umum (rasio kejadian/1,000 orang-tahun, 7.56) dan 4472
pasien dengan psoriasis (rasio kejadian/1,000 orang-tahun, 10.94).
 Pada analisis yang tak disesuaikan, psoriasis dihubungkan dengan peningkatan 3.9% resiko
untuk KMKB per tambahan tahun durasi penyakit, dan pada analisis multivariabel, resiko untuk
KMKB meningkat 1.0% per tambahan tahun durasi psoriasis. Untuk nilai akhir sekunder, hazard
ratios multivariabel yang dihubungkan dengan durasi psoriasis adalah, masing-masing, 1.006 untuk
infark miokard, 1.011 untuk stroke iskemik, dan 1.011 untuk kematian KV.

PEMBAHASAN
Kami menggunakan studi pencitraan manusia dan studi berbasis populasi untuk menyelidiki
apakah durasi penyakit psoriasis meningkatkan resiko untuk PKV dan KMKB, dan kami telah
berhasil memiliki bukti meyakinkan untuk dapat mengusulkan bahwa efek durasi psoriasis terhadap
PJK sudah melampaui faktor resiko KV tradisional, bahkan pada pasien dengan resiko KV rendah.
Dicatat pula, setiap peningkatan 1 SD pada durasi psoriasis meningkatkan RTLB sebanyak 2.5%,
dimana menunjukkan bahwa secara kasar ada peningkatan 10% untuk efek samping inflamasi
vaskuler jangka panjang pada basis studi populasi.
Seperti pada kasus studi-studi rheumatoid artritis, kebanyakan studi sudah menghubungkan
psoriasis dengan peningkatan resiko untuk PKV, namun data menunjukkan bahwa faktor resiko
klasik KV saja tidak sepenuhnya menangkap peningkatan resiko ini, dan inflamasi sistemik telah
dimajukan sebagai penjelasan potensial untuk hubungan antara psoriasis dan PKV. Sejalan dengan
ini, inflamasi juga dihubungkan dengan kerusakan sensitifitas insulin, penebalan intima-media
karotis, disfungsi endotel, kekakuan aorta, inflamasi vaskuler, dan plak koroner, dengan para
penanda PKV ini terjadi lebih sering pada pasien dengan psoriasis. Hal ini bisa terjadi karena
kerusakan pembuluh darah secara konsisten ini berkonsekuensi terhadap aktivasi imun pada mereka
dengan durasi penyakit yang lebih lama.
Kami memilih pendekatan epidemiologis transisional, menggunakan studi pencitraan
manusia yang digabungkan dengan data observasional registri untuk menekankan relevansi klinik
peningkatan inflamasi vaskuler yang terlihat pada studi kami. Secara spesifik, kami menemukan
peningkatan sebesar 1% pada resiko kejadian KV masa depan per tambahan 1 tahun durasi
penyakit, dimana ukuran efek ini mirip dengan yang ditemukan pada orang merokok. Masing-
masing komponen dari hasil komposit KMKB juga meningkat dengan semakin lamanya durasi
penyakit, yang mengindikasikan bahwa durasi inflamasi meningkatkan semua penyakit yang
berhubungan dengan kelainan vaskuler. Biarpun itu, kami menekankan bahwa hubungan
independen antara psoriasis dan PKV masih menjadi topik perdebatan yang berjalan, sebagaimana
juga efek terapi sistemik terhadap inflamasi vaskuler dan kejadian KV itu sendiri.
 Hambatan pada kohort populasi merupakan kurangnya informasi mengenai IMT dan
intensitas olharaga subjek. Namun, data tersebut tersedia pada kohort NIH, dan penyesuaian untuk
IMT tidak mengubah secara signifikan pada hubungan antara durasi penyakit dan inflamasi
vaskuler. Selain itu, PKV sebelumnya dan diabetes, yang merupakan dua prediktor mayor untuk
KMKB pada kohort populasi, tidak berhubungan dengan inflamasi vaskuler pada kohort NIH. Hal
ini kemungkinan dikarenakan rendahnya jumlah pasien dengan karakteristik tersebut pada kohort
NIH. Kelebihan yang penting termasuk banyaknya jumlah subjek penelitian dan akurasi yang tinggi
dari registri tingkat nasional, yang akhirnya meminimalkan bias karena jenis kelamin, usia,
pengobatan saat ini, dan status sosioekonomi. Suatu data observasional dengan sendirinya tidak
cukup untuk menetapkan kausalitas. Namun, temuan-temuan sebanding yang ditemukan di berbagai
populasi, yang didapatkan dengan menggunakan kedua pendekatan kami yaitu data observasional
dan pencitraan vaskuler, menambah kekuatan dan kredibilitas temuan kami, dan hasilnya konsisten
dengan temuan sebelumnya yang mendemonstrasikan bahwa durasi psoriasis merupakan faktor
resiko independen untuk infark miokard dan penyakit arteri koroner yang diukur dengan angiografi.
Kesimpulannya, kami telah menyediakan bukti baru yang kuat bahwa durasi psoriasis
meningkatkan inflamasi vaskuler dan resiko untuk terjadinya KMKB. Para penyedia jasa pelayan
kesehatan harus mempertimbangkan untuk menanyakan durasi psoriasis saat menilai stratifikasi
resiko KV.

Daftar Pustaka:
1. Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am
Acad Dermatol. 2006;55:829-835.
2. Gelfand JM, Azfar RS, Mehta NN. Psoriasis and cardiovascular risk: strength in numbers. J Invest Dermatol. 2010;130:919-922.
3. Gelfand JM, Mehta NN, Langan SM. Psoriasis and cardiovas- cular risk: strength in numbers, part II. J Invest Dermatol. 2011; 131:1007-1010.
4. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA.
2006;296:1735-1741.
5. Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular
mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31: 1000-1006.
6. Mehta NN, Yu Y, Saboury B, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-
fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol. 2011;147:1031-1039.
7. Mehta NN, Torigian DA, Gelfand JM, Saboury B, Alavi A. Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F]
fluorodeoxyglucose positron emis- sion tomography/computed tomography (FDG-PET/CT). J Vis Exp. 2012:e3777.
8. Naik HB, Natarajan B, Stansky E, et al. Severity of psoriasis associates with aortic vascular inflammation detected by FDG PET/CT and neutrophil
activation in a prospective observa- tional study. Arterioscler Thromb Vasc Biol. 2015;35:2667-2676.
9. Egeberg, Alexander (2017). ‘‘JAAD-D-17-00307 Supplementary Materials’’, Mendeley Data, v2. http://dx.doi.org/10.17632/ t7syfrg4yr.2.
10. Fayad ZA, Mani V, Woodward M, et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality
imaging (dal-PLAQUE): a rando- mised clinical trial. Lancet. 2011;378:1547-1559.
11. Figueroa AL, Abdelbaky A, Truong QA, et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of
future CV events. JACC Cardiovasc Imaging. 2013;6:1250-1259.
12. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a
meta-analysis of observational studies. Ann Rheum Dis. 2012;71:1524-1529.
13. Egeberg A, Thyssen JP, Jensen P, Gislason GH, Skov L. Risk of myocardial infarction in patients with psoriasis and psoriatic arthritis: a
nationwide cohort study. Acta Derm Venereol. 2017;97: 819-824.
14. Parisi R, Rutter MK, Lunt M, et al. Psoriasis and the risk of major cardiovascular events: cohort study using the Clinical Practice Research
Datalink. J Invest Dermatol. 2015;135: 2189-2197.
15. Dowlatshahi EA, Kavousi M, Nijsten T, et al. Psoriasis is not associated with atherosclerosis and incident cardiovascular events: the Rotterdam
Study. J Invest Dermatol. 2013;133: 2347-2354.
16. Boehncke WH, Boehncke S, Tobin AM, Kirby B. The ’psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity.
Exper Dermatol. 2011;20: 303-307.
17. Balci DD, Balci A, Karazincir S, et al. Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis. J Eur Acad
Dermatol Venereol. 2009;23:1-6.
18. Gyldenlove M, Storgaard H, Holst JJ, Vilsboll T, Knop FK, Skov L. Patients with psoriasis are insulin resistant. J Am Acad Dermatol.
2015;72:599-605.
19. Ogdie A, Troxel AB, Mehta NN, Gelfand JM. Psoriasis and cardiovascular risk: strength in numbers. Part 3. J Invest Dermatol. 2015;135:2148-
2150.
20. Bissonnette R, Harel F, Krueger JG, et al. TNF-alpha antagonist and vascular inflammation in patients with psoriasis vulgaris: a randomized
placebo-controlled study. J Invest Dermatol. 2017; 137:1638-1645.
21. Li WQ, Han JL, Manson JE, et al. Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study. Br J Dermatol.
2012;166:811-818.
22. Armstrong AW, Harskamp CT, Ledo L, Rogers JH, Armstrong EJ. Coronary artery disease in patients with psori- asis referred for coronary
angiography. Am J Cardiol. 2012;109: 976-980.