Arthritis as an important determinant for psoriatic patients to develop severe
vascular events in Taiwan: A nation-wide study
Yi-Ying Chin1,2, Hsin-Su Yu1, Wan-Chen Li1, Ying-Chin Ko3, Gwo-Shing Chen1,
Ching-Shuang Wu4, Yi-Wei Lu1, Yi-Hsin Yang5, Cheng-Che E. Lan1,2
1. Department of Dermatology, Kaohsiung Medical University Hospital, and
Department of Dermatology, College of Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan
2. Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaoshiung
Medical University, Kaohsiung, Taiwan
3. Department of Public Health and Environmental Medicine, Faculty of Medicine,
College of Medicine, Kaohsiung Medical University, Taiwan
4. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical
University, Kaohsiung, Taiwan
5. School of Pharmacy, College of Pharmacy, Kaohsiung Medical University
Conflict of interest: None
Key words: Psoriasis, arthritis, vascular events, methotrexate
Running Head: psoriasis with or without joint involvement
Word count: 3026
Tables: 5
Figure: 1
Corresponding authors: Cheng-Che Lan or Yi-Hsin Yang, 100 Shih-Chuan 1st Rd,
Kaohsiung, Taiwan. E-mail: laneric@gmail.com, yihsya@kmu.edu.tw
1
Abstract
Background: Psoriasis is an important systemic inflammatory disease that often leads
to severe vascular diseases. This study was launched to determine if joint
involvement affects incidence of vascular comorbidities in psoriatic patients.
In
addition, potential vasculo-protective effects of methotrexate in psoriatic patients
were also evaluated.
Method: A population-based retrospective cohort study was conducted using the
Taiwanese National Health Insurance database spanning from 1996 to 2006.
Accordingly, 7648 and 284 psoriatic patients without or with arthritis, respectively,
were identified.
To ensure the temporal relationship between different events, those
with date of first diagnosis psoriasis during the year of 1996 were excluded from
subsequent analyses.
In addition, those with diagnosis of cerebrovascular or
cardiovascular diseases prior to onset of psoriasis were also excluded from relevant
subsequent analyses.
Result: Taking psoriatic patients without arthritis as the referent group, the hazard
ratio for incident cerebrovascular disease was 1.82 (95% CI=1.17-2.82) for psoriatic
patient with arthritis.
In addition, psoriatic patients without arthritis who had
methotrexate treatment showed reduced risks for incident cerebrovascular disease as
compared to those with no arthritis and had received no methotrexate/retinoid
2
treatment.
Similar analyses were performed on cardiovascular diseases, and
equivalent results were obtained.
Conclusion: Our study indicated that arthritis is a potential determinant for psoriatic
patients in terms of incident vascular comorbidities.
In addition, methotrexate
treatment may be associated with reduced risks for development of severe vascular
diseases in psoriatic patients without arthritis.
Further studies should focus on the
clinical complications associated with psoriatic patients with or without arthritis.
Key words: Psoriasis, Psoriatic arthritis, cerebrovascular disease, cardiovascular
disease, methotrexate
3
Psoriasis is a chronic inflammatory disease characterized by keratinocyte
abnormalities and immune dysfunctions.
The prevalence of this disease among
different ethnic groups ranged between 0.5~3% with lower rates for Asians.1
studies on psoriasis focused on skin and joint complaints.
Classic
In 1995, Henseler et al
reported the association between psoriasis, metabolic syndrome, and cardiovascular
complications.2
Subsequently, similar findings were reproduced in different studies
performed from different regions of the world.3-5
Cerebrovascular and
cardiovascular diseases are severe vascular events associated with patients with
psoriasis and have large negative impacts on life quality and expectancy.
The
concept of “Psoriatic March” was proposed explaining how severe psoriasis may
drive the development of cardiovascular comorbidity.6
According to this concept,
psoriasis is a disease with systemic inflammation that may cause insulin resistance,
trigger endothelial cell dysfunction, leading to atherosclerosis and finally resulting in
stroke or myocardial infarction.6
Psoriatic arthritis, a classic component of psoriasis, has an estimated frequency in
psoriatic patients varying from 1% to 25%, again with a lower prevalence among
Asians.7-9
Like psoriasis, patients with psoriatic arthritis per se were reported to
have higher prevalence rates of metabolic syndromes and cardiovascular
4
comorbidities as compared to general population.10,11
In patients with psoriasis, the
presence of joint involvement may indicate a different disease course.
In fact, our
previous study has shown that peripheral monocytes from psoriatic patients with
arthritis showed higher levels of heavy-chain expression on the cell surface as
compared to those without.12
This result suggested that different mechanisms may
be involved in the pathogenesis among psoriatic patients with or without arthritis.
From genetic association studies, it was shown that sibling recurrence risk is
estimated to be much higher for psoriatic patients with joint involvement as compared
to those without.13-16 More recently, IL-13 was suggested to be a risk locus for
psoriatic patients with joint involvement but not those without.17,18
Several studies
had shown that psoriatic patients with joint involvements are more likely to have
more severe disease course.
Psoriatic patients with arthritis were reported to have
higher psoriasis activity and severity index (PASI) scores19 and lower quality of life20
than those without.
Serum levels of highly sensitive CRP were also reported to be
higher in psoriatic patient with joint involvement.21
These results suggested that
for psoriatic patients, presence of arthritis may indicate a condition with more severe
disease activity and higher inflammatory status.
In support with this notion, Husted
et al. has recently showed that psoriatic patients with joint involvement are more
likely to have cardiovascular complications than those without.22
5
Another intriguing issue to evaluate is if treatment strategies should differ for
psoriatic patients with or without arthritis.
Previously, it has been proposed that
effective methotrexate treatment may be associated with reduced incidence of severe
vascular events in patients with psoriasis.5,23
How concomitant presence of arthritis
modifies the protective effects of methotrexate for psoriatic patients is an intriguing
clinical question that may provide important therapeutic insights for psoriatic patients.
Using the National Health Insurance (NHI) database in Taiwan, we aimed to evaluate
the risks of severe vascular complications and how methotrexate and retinoid, the two
most commonly prescribed systemic treatment for psoriasis in Taiwan, modify these
risks in psoriatic patients with or without arthritis.
6
Material and method
The National Health Insurance (NHI) Program in Taiwan was launched in1995.
This
program covers all inpatient and outpatient medical services including primary and
secondary caring episodes as well as the cost of prescription drugs with various
co-payment rates from the patients.
In 2010, the coverage rate of NHI program is
99.5% of Taiwan’s 22.96 million population.
A population-based retrospective
cohort study was conducted based on the Longitudinal Health Insurance Database
2005 (LHID2005, years 1996-2006), which contains all the original inpatient and
outpatient physician claims and prescription drug claims as well as demographic
information of 1,000,000 beneficiaries, randomly sampled from the year 2005
Registry for Beneficiaries (ID) of the NHI research database.
The LHID 2005 and
the original NHI database are not significantly different in the gender, age distribution
or average insured payroll-related amount between the patients.
Confidentiality
assurances were addressed by abiding the data regulations of the Bureau of NHI.
The ICD9 (International Classification of Diseases, revision 9) codes were used to
identify medical conditions from the database of inpatient and outpatient physician
claims during 1996-2006 as previously described.5
Patients with years of birth
between 1930 to 1990 were included for analysis. To ensure no prior history of
psoriasis for at least one year, those with date of first diagnosis during the year of
7
1996 were excluded (ICD9 codes 696.1, 696.8).
diagnosis were considered as the index date.
The dates of first psoriasis
The psoriatic patients who had also
received a diagnostic code of arthritis (ICD9 codes 696.0) were defined as psoriatic
patients with joint involvement.
The primary endpoint of event was the occurrence of severe vascular disease
(cerebrovascular diseases: ICD9 codes 430.0-438.9; cardiovascular diseases: ICD9
codes 410-414.05, 414.10, 414.11, 414.19, 414.8-414.9, 429.79) documented by the
physician claims.
Those with diagnostic codes of severe vascular disease prior to
index dates (onset of psoriasis) were excluded from the study to ensure the temporal
relationship between index date and development of vascular events.
The duration
of follow-up for patients with severe vascular event was the time between index date
and the date of first severe vascular disease diagnosis in either inpatient or outpatient
records, and for the censored time of patients without severe vascular event was from
the index dates to the end of year 2006 or the date of withdrawing from NHI program.
Prescriptions of methotrexate, retinoid, and phototherapy were identified from the
database of Details of Ambulatory Care Orders, and the indicator variables of users
versus non-users were constructed in the statistical analysis.
Systemic methotrexate
and retinoid were chosen because they are the most commonly prescribed systemic
treatment for psoriasis in Taiwan.
To avoid possible confounder resulting from
8
alternating between methotrexate and retinoid, we excluded psoriatic patients who
had received both methotrexate and retinoid regimen.
Additional covariates also
included physician claims of hypertension (ICD9 codes 410.00-405.9), diabetes
(ICD9 codes 250.00-250.9) and dyslipidemia disease (ICD9 codes 272.0-272.4) as
well as age and gender.
It should be noted that the reliability and validity of ICD9
diagnoses and medication history in this dataset have been validated previously.24
To investigate the risk of developing severe vascular disease for psoriatic patients, the
Cox proportional hazards models were adopted to analyze the time to severe vascular
disease diagnosis while excluding any persons with severe vascular disease diagnosis
in the year before index dates. Descriptive data are presented as frequencies or
percentages. Pearson chi-square tests were performed between the psoriatic patients
with or without arthritis.
A p-value <0.05 was considered statistically significant.
Figure 1 demonstrates a flow chart used for categorizing participants and analyzing
different scenarios in this study.
Accordingly, 7622 and 7455 psoriatic patients
fulfilled the criteria for analyses focusing on cerebrovascular and cardiovascular
diseases, respectively.
9
Results
Demographic and clinical characteristics of psoriatic patients with or without
arthritis.
As demonstrated in Table 1, 7932 patients with psoriasis were included in
this study.
Among the study population, 7648 and 284 patients were without or with
joint involvement, respectively.
The male gender is more susceptible to develop
psoriasis as compared to the female counterpart, regardless of the joint involvement.
The age of patients with arthritis was slightly older than those without.
The
prevalence of metabolic disorders (including hypertension, DM, and dyslipidemia)
were significantly higher in the psoriatic patient with joint involvement group as
compared to those without.
In addition, psoriatic patients with joint involvement
were more likely to receive methotrexate and retinoid systemic therapy as compared
to patients with no arthritis.
The mean follow-up days of psoriatic patients without
and with arthritis were 3428.49 ± 11.20 and 3235.15 ± 60.36 days, respectively, in the
cerebrovascular analyses.
In parallel, the mean follow-up days of psoriatic patients
without and with arthritis were 3274.93 ± 14.48 and 3085.14 ± 70.49 days, in the
cardiovascular analyses.
No differences in terms of follow-up days were noted
between psoriatic patients without or with arthritis.
The prevalence of severe
vascular events was higher in psoriatic patients with arthritis (23.9%) as compared to
those without (21.6%), but no statistic significance was found.
10
Taking the temporal relationship into consideration, psoriatic patients without
joint involvement were less likely to have incident cerebrovascular events as
compared to those with arthritis.
To compare the incidences of cerebrovascular
events between psoriatic patients with or without arthritis, further analyses were
performed.
Accordingly, patients with diagnosis of cerebrovascular disease prior to
index date were excluded from analyses to ensure temporal relationship between
onset of psoriasis and development of cerebrovascular events as described in the
method section.
Since we had previously shown that age, sex, hypertension, DM,
hyperlipidemia,
and
phototherapy
all
contribute
to
the
development
of
cerebrovascular disease,5 these covariates were included in our models for adjustment.
As demonstrated in table 2, univariate analyses for evaluating the risks of psoriatic
patients to develop cerebrovascular disease by arthritis and medication status showed
that presence of arthritis was associated with higher risks to develop cerebrovascular
disease while use of methotrexate/retinoid were associated with reduced risks.
However, no statistic significance was associated with these trends. After adjusting
for relevant confounders for cerebrovascular disease in the multivariate analyses, we
found the hazard ratio of newly developed cerebrovascular disease to be 1.82 (95%
CI=1.17-2.82; p=0.007) for psoriatic patients with arthritis as compared to those
without.
In addition, methotrexate prescription was associated with reduced risk for
11
developing cerebrovascular disease while retinoid prescription showed no significant
effect.
Methotrexate
treatment
is
associated
with
reduced
occurrences
of
cerebrovascular events in psoriatic patients without arthritis.
Due to potential clinical implications, we further classified psoriatic patients
according to presence of arthritis even though the interaction between joint
involvement and medication used was not significant statistically (p=0.682).
Accordingly, methotrexate prescription was associated with reduced incidence of
cerebrovascular events for psoriatic patients without arthritis while no significant
protective effect was found for patients with retinoid only prescription.
No
protective effect was found for psoriatic patients with arthritis, regardless of the
therapeutic prescriptions received (Table 3).
Psoriatic patients without arthritis were less likely to have incident
cardiovascular events as compared to those with arthritis.
Cardiovascular event
is another severe vascular complication frequently associated with patients with
psoriasis.
Since we have evaluated the effect of joint involvement on psoriatic
patients in terms of incident cerebrovascular disease, we next examine the relationship
between psoriasis and incident cardiovascular events following similar analytic
strategy.
Accordingly, psoriatic patients with arthritis are 1.46 folds (95%CI
12
1.01-2.09; p=0.042) more likely to have incident cardiovascular disease as compared
to those without after adjusting for relevant confounders in the multivariate analyses.
In addition, both methotrexate and retinoid prescription were associated with reduced
risk for developing cerebrovascular disease. (Table 4)
Methotrexate and retinoid treatment is associated with reduced occurrences of
cardiovascular events in psoriatic patients without arthritis.
When categorized patients according to joint involvement, both methotrexate and
retinoid monotherapy reduced the risks of incident cardiovascular events in psoriatic
patients without arthritis while no significant effect was found for patients with joint
involvement (table 5).
13
Discussion
In this nation-wide study focused on psoriasis, several important issues were
revealed.
First of all, we found arthritis as an important determinant for psoriatic
patients to develop severe vascular events in Taiwan.
Previous studies have shown
that psoriatic patients, regardless of joint involvement, are more likely to have
components of metabolic syndromes and severe vascular complications than general
population.2-5
Furthermore, psoriatic arthritis per se is associated with subclinical
atherosclerosis revealed by increased intima-media thickness, which is associated
with increased risks for cardiovascular complications.25
The report from Husted et
al. found higher prevalence of cardiovascular comorbidities in psoriatic patients with
joint involvement.22
Taking a step further, the current study demonstrated that
psoriatic patients with arthritis are more likely to develop severe vascular
complications than those without after adjusting for potential confounders.
Secondly,
the current study also suggested that methotrexate treatment is associated with
reduced risks for both incident cerebrovascular and cardiovascular diseases in
psoriatic patients without arthritis.
Previously, it has been proposed that
methotrexate provides protective effects against incident severe vascular events
through its anti-inflammatory and anti-thrombotic effects.5
In addition, it has been
shown that effective systemic therapy may ameliorate cardiovascular risk profiles of
14
psoriatic patients.26,27 As mentioned previously, psoriatic patients with arthritis were
associated with higher PASI scores and higher CRP levels as compared to those
without.19,21
Therefore, methotrexate treatment may reduce the risks for developing
severe vascular complications in certain subsets of psoriatic patients with less severe
systemic inflammatory status.
Our database, however, does not contain information
on severity of disease to validate this hypothesis.
Another intriguing phenomenon
noted is that retinoid therapy is associated with reduced risks for development of
cardiovascular diseases.
This finding appeared paradoxical since while protective
effects for cardiovascular disease were found for systemic retinoid therapy, similar
risk reduction was not found for cerebrovascular disease.
One possible explanation
is that minor atherosclerosis of coronary arteries may be asymptomatic to patients and
not recorded by physicians.
On the other hand, minor atherosclerosis in small
cerebral vessels can often elicit symptoms suggestive of cerebrovascular event, a
condition that would likely urge patients to request for medical workup and
documentation.
Therefore, the intrinsic differences in disease recognition sensitivity
may have contributed to this discrepancy.
these intriguing possibilities.
Further studies are warranted to clarify
It should also be noted that in this study, patients who
had received systemic methotrexate or retinoid treatment were not associated with
higher risks for developing severe vascular diseases. As proposed in our previous
15
study,5 it is possible that certain “physician selection bias” may be present in Taiwan
among physicians treating psoriasis that results in prescription of systemic
methotrexate/retinioid to patients in good health condition.
Phototherapy, on the
other hand, is associated with increased risks for incident cerebrovascular events in
Taiwan.5
It should be noted that although the analysis regarding the implications of
treatment effect on different subgroups of psoriatic patient are intriguing, these results
are preliminary given the low rates of events observed.
Additional studies with
larger cohort should be performed to validate these findings.
Several important points should be noted regarding the design of this study.
First
of all, using the NHI data source from 1996~2006, we were able to exclude subjects
with the diagnoses of cerebrovascular and cardiovascular disease before the index
date.
In addition, to ensure no prior history of psoriasis for at least one year, we also
excluded those with date of first diagnosis during the year of 1996.
It is noted that
diagnosis of psoriasis prior to 1996 cannot be identified in this database.
However,
as psoriasis is a chronic, relapsing disorder, we expect majority of psoriatic patients
with onset of disease prior to 1996 to seek medical attention sometime during 1996,
and therefore, will be accounted for and excluded from our analyses.
This approach
enabled us to establish the temporal relationship between development of psoriasis
and severe cardiovascular events.
It is also noted that instant cardiovascular or
16
cerebrovascular death may be undocumented by the LHID dataset if the deceased are
not sent to hospital or seen by physician at home.
However, since medical facilities
in Taiwan are easily accessible and the NHI covers more than 99.5% of the Taiwanese
population, the impact of unrecorded fatal events in this study is probably minimal.
Several other limitations included in this study should be mentioned.
Certain
background confounding factors such as smoking habits, alcohol consumption, body
mass index or circulating levels of inflammatory markers were not available to be
included for analyses in this study.
In addition, since this study used ICD-9 codes
to determine the presence of medical condition, it is difficult to validate whether
the coding was both accurate and comprehensive.
However, since this study
included a rather large cohort of psoriatic patients, it is unlikely that significant
differences in coding accuracy exist between groups with or without arthritis.
It
is worthy to note that the estimated prevalence of joint involvement in our cohort is
around 3.6%, which is lower than the worldwide prevalence around 5~25%.
It is
possible that only psoriatic patients with more severe arthritis are properly coded in
the study and that may have affected our results.
Therefore, how severity of arthritis
may modify the risk of psoriatic patients to develop vascular comorbidities is an
intriguing issue for further investigation.
Another explanation for the low
prevalence of joint involvement in this study may result from our inclusion criteria.
17
More specifically, we first selected patients with diagnostic codes for psoriasis, then
screened for additional code for psoriatic arthritis to ensure all patients enrolled have
psoriatic skin lesions.
It is likely that some patients only have psoriatic arthritis.
As mentioned previously, psoriatic patients with or without joint involvement may
have different clinical course and harbor distinct genetic background. Patients with
psoriatic arthritis without concomitant skin lesions likely represent a distinct scenario.
This study focused on psoriatic patients with skin lesion. Further studies focusing on
patients with psoriatic arthritis sine psoriasis is warranted.
It is important to note
that the prevalence of psoriasis has been shown to vary among different ethnic groups.
In an epidemiology study from China consisting of 670,000 persons, the prevalence of
psoriasis was approximately 0.3%.28
0.1%.29
In Japan, the prevalence of psoriasis was about
Among the Japanese psoriatic patients, only about 1-3% develop psoriatic
arthritis.9,29
Therefore, although no formal validation was done for diagnostic codes
for psoriasis and psoriatic arthritis in this study, the relatively low prevalence profiles
observed in this study consisting of Taiwanese population appeared reasonable.
However, the relatively small numbers of psoriatic patients with arthritis may also
have an impact on our statistical analyses. Further studies consisting of different
ethnic groups with higher prevalence of psoriatic arthritis should be performed.
In summary, our results indicated that arthritis is an important determinant for
18
psoriatic patients to develop severe vascular events in Taiwan.
In addition,
methotrexate treatment may be associated with reduced risks for developing severe
vascular diseases in psoriatic patients, especially those without joint involvement.
Further prospective study consisting of larger patient population should be conducted
to validate the vasculo-protective effect of this treatment strategy and clarify the
impact joint involvement on development of vascular comorbidities for psoriatic
patients.
19
Conflict of Interest: None
Acknowledgement
This study was supported by research grants from Center of Excellence for
Environmental Medicine, Kaohsiung Medical University and Kaohsiung Medical
University Research Foundation (KMUER-R03).
This study is based in part on data from the National Health Insurance Research
Database provided by the Bureau of National Health Insurance, Department of Health
and managed by National Health Institutes. The interpretation and conclusion
contained herein do not represent those of Bureau of National Health Insurance,
Department of Health or National Health Research Institutes.
20
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25
Table1. Demographic information of psoriatic patients included in this study
Psoriatic patients
Without arthritis
N
total
sex
age
%
7648
with arthritis
n
%
284
female
3494
45.7%
112
39.4%
male
4154
54.3%
172
60.6%
11-20
447
5.8%
5
1.8%
21-30
1024
13.4%
22
7.7%
31-40
1423
18.6%
54
19.0%
41-50
1374
18.0%
63
22.2%
51-60
1520
19.9%
77
27.1%
61-70
918
12.0%
28
9.9%
71-80
942
12.3%
35
12.3%
Mean±SD
P value
47.40 ± 17.38
49.95 ± 15.22
0.038
<0.001
0.006
Hypertension
2128
27.8%
105
37.0%
0.001
Diabetes mellitus
1408
18.4%
73
25.7%
0.002
Dyslipidemia
1855
24.3%
93
32.7%
0.001
Severe vascular disease
1651
21.6%
68
23.9%
0.344
Methotrexate prescription
245
3.3%
145
51.0%
<0.001
Retinoid prescription
251
3.3%
84
29.6%
<0.001
26
Table 2. Risk of psoriatic patients developing cerebrovascular disease by arthritis and
medication use (I).
univariate Cox regression
95% CI
N of
Total N
*multivariate Cox regression
HR
Events
95% CI
P value
HR
Lower Upper
P value
Lower Upper
Arthritis
no
7397
383
1.00
1.00
yes
225
23
1.50
7189
383
1.00
MTX only
240
10
0.61
0.32
1.13
0.117
Retinoid only
193
13
0.96
0.55
1.68
0.897
0.98
2.29
0.059
1.82
1.17
2.82
0.007
0.45
0.23
0.85
0.015
0.73
0.41
1.30
0.284
Medication used
no MTX and no
1.00
Retinoid
N: Number
HR: Hazard ratio
CI: Confidence Interval
MTX: methotrexate
*Adjusted for age, sex, hypertension, diabetes, dyslipidemia, and phototherapy
27
Table 3 Risk of psoriatic patients developing cerebrovascular disease by arthritis and
medication status (II).
Psoriatic patients without arthritis
Psoriatic patients with arthritis
95% CI
95% CI
N of
N
N of
HR
P value
N
Event
HR Low Upper P value
Events
Lower Upper
er
Medication used
no MTX and no Retinoid 7069 368
1.00
MTX only
160
6
0.42
0.19
0.95
Retinoid only
168
9
0.67
0.35
1.31
120
15
1.00
0.038
80
4
0.62 0.20
1.95
0.416
0.245
25
4
0.83 0.26
2.67
0.760
Interaction between arthritis and medication used, P value=0.682
N: Number
HR: Hazard ratio
CI: Confidence Interval
MTX: methotrexate
Adjusted for age, sex, hypertension, diabetes, dyslipidemia
28
Table 4 Risk of psoriatic patients developing cardiovascular disease by arthritis and
medication status (I).
univariate Cox regression
95% CI
N of
Total N
*multivariate Cox regression
HR
Events
95% CI
P value HR
Lower Upper
P value
Lower Upper
Arthritis
no
7230
655
1.00
1.00
yes
225
33
1.25
7038
655
1.00
MTX only
226
16
0.59
0.36
0.98
0.040
Retinoid only
191
17
0.72
0.44
1.16
0.180
0.88
1.78
0.208
1.46
1.01
2.09
0.042
0.48
0.29
0.81
0.005
0.52
0.31
0.85
0.009
Medication used
no MTX and no
1.00
Retinoid
N: Number
HR: Hazard ratio
CI: Confidence Interval
MTX: methotrexate
*Adjusted for age, sex, hypertension, diabetes, dyslipidemia, and phototherapy
29
Table 5. Risk of psoriatic patients developing cerebrovascular disease by arthritis and
medication use (II).
Psoriatic patients without arthritis
Psoriatic patients with arthritis
95% CI
95% CI
N of
N
N of
HR
P value
N
Events
HR Low Upper P value
Events
Lower Upper
er
Medication used
no MTX and no Retinoid 6913 634
1.00
MTX only
152
9
0.39
0.20
0.76
Retinoid only
165
12
0.47
0.26
0.83
125
21
1.00
0.005
74
7
0.79 0.33
1.89
0.590
0.009
26
5
0.64 0.23
1.82
0.407
Interaction between arthritis and medication used, P value=0.246
N: Number
HR: Hazard ratio
CI: Confidence Interval
MTX: methotrexate
Adjusted for age, sex, hypertension, diabetes, dyslipidemia
30
Figure1: Study Design
Patient selection
Longitudinal Health Insurance Database 2005
(LHID2005, years 1996-2006)
Psoriatic patients, n=7932
(without arthritis, n=7648; with arthritis, n=284)
cerebrovascular diseases
Patient selection criteria:
1. psoriasis (ICD-9-CM codes 696.1, 696.8)
2. Inclusion: Patients with years of birth between 1930 to 1990.
3. Exclusion: the date of first psoriasis diagnosis during the year of 1996.
The date of severe vascular disease (cerebrovascular/cardiovascular
diseases) diagnosis before the psoriatic diagnosis and psoriatic patients
who had received both MTX and retinoid were excluded from analysis.
cardiovascular diseases
Analysis: Cox proportional hazards model
psoriatic patients without
arthritis, n=7397
psoriatic patients with
arthritis, n=225
psoriatic patients without
arthritis, n=7230
psoriatic patients with
arthritis, n=225
Covariates: Age, gender, hypertension, diabetes and dyslipidemia
disease, phototherapy, medications (MTX/Retinoid)
Follow up
Index date:
the date of first psoriasis
diagnosis.
The primary endpoint of event:
severe vascular disease
(cerebrovascular/cardiovascular diseases).
Censoring:
the end of year 2006 or the date of
withdrawing from NHI program.
31