Psoriasis is an immune disease and typically characterized by erythematous papules and plaques with silver scaling. Growing evidence shows that patients with psoriasis have more comorbidities and conventional cardiovascular risk factors than the general population.1 Psoriasis also has been found to cause increased carotid intimal thickness as well as systemic inflammatory markers, suggesting that psoriasis might be associated with an increased risk of atherosclerosis.2 However, the association between psoriasis and ischemic stroke was still controversial.3–5 Therefore, we conducted a nationwide population-based study using the Taiwan National Health Insurance (NHI) database to investigate the impact of psoriasis on the development of ischemic stroke.
The NHI program has operated since 1995 and includes 99.5% of the population in Taiwan. The NHI Research Database contained the complete NHI claims and had released a cohort dataset made of 1 000 000 randomly sampled people. This study was a population-based study with a retrospective cohort design. The patients for the study group with first-time recorded psoriasis were identified by following enrollment criteria: (i) ≥18 years old; and (ii) having at least two consensus psoriasis diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 696, psoriasis and similar disorders; 696.0, psoriatic arthropathy; 696.1, other psoriasis; 696.8, other psoriasis and similar disorders), at least one made by a dermatologist or a rheumatologist, between 2000 and 2002. The exclusion criteria were: (i) patients with diagnosis of psoriasis before 1 January 2000; or (ii) patients who had been diagnosed as having ischemic stroke (ICD-9-CM codes 433–435) before enrollment. Their first ambulatory care visits or hospital admissions with a principle diagnosis of psoriasis were assigned as the date of enrollment. A comparison group was selected from the remaining subjects having no psoriasis between 1995 and 2007 and no ischemic stroke before enrollment. They were matched with psoriasis patients in terms of age, sex, some medical disorders including hypertension, diabetes, dyslipidemia, and the date of enrollment. Other covariate variables including chronic kidney disease, coronary artery disease, atrial fibrillation, valvular heart disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were also reviewed in this database.
Finally, 2783 patients with first-recorded psoriasis were included as the study group and another 13 910 controls were included as the control group. Each patient in this study was individually tracked for 5 years from the date of enrollment to identify who had diagnosis of new-onset ischemic stroke as reaching the end-point of this study.
The occurrence of ischemic stroke was identified by insurance claim as the main diagnosis during hospitalization or subsequent outpatient department visits. The event was further identified by any one of the following conditions: (i) hospitalization claims; (ii) more than three consecutive outpatient visits to hospitals, followed either by claims for various neurological imaging technology and long-term prescriptions used for ischemic stroke; or (iii) by claims for rehabilitation and the long-term ischemic stroke prescriptions.
All data were expressed as the frequency (percentage) for ordinal and categorical data or mean ± standard deviation (SD) for continuous data. The continuous data between the study group and comparison group were compared by Student’s t-test. The categorical data between them were compared with χ2-test and Yates’ correction or Fisher’s exact test as appropriate. Ischemic stroke-free survival analysis was assessed using Kaplan–Meier analysis, with the significance based on the log–rank test. Multiple regression analysis was carried out by using Cox proportional hazards regression analysis. Statistical significance was inferred at a two-sided P-value of less than 0.05.
In a total of 16 693 selected patients, the mean ages were 45.3 years for 13 910 patients with new-onset psoriasis and 45.3 years for 2783 controls. The baseline characteristics of the two groups are shown in Table 1. There was no significant difference in age, sex and incidence of comorbidities except SLE and RA between the two groups. Interestingly, we found that psoriasis patients had a higher incidence of SLE and RA in the current study. This may be related to some similar clinical manifestations and gene polymorphisms like LCE3C_LCE3B-del resulting in those conditions.6 During the 5-year follow-up period, 718 patients suffered from the development of ischemic stroke: 143 stroke episodes (5.1%) from psoriatic patients and 575 (4.1%) from the comparison group. Patients with new-onset ischemic stroke had higher incidence of psoriasis than those without ischemic stroke (19.9% vs 16.5%, P < 0.001).
|With newly diagnosed psoriasis||P-value|
|No (n = 13 910)||Yes (n = 2783)|
|Age, years||43.5 ± 17.4||45.3 ± 17.4||0.980|
|Male, n (%)||7830 (56.3)||1567 (56.3)||1.000|
|Hypertension, n (%)||2620 (18.8)||525 (18.9)||0.980|
|Diabetes, n (%)||1577 (11.3)||316 (11.4)||0.976|
|Dyslipidemia, n (%)||1900 (13.7)||381 (13.7)||0.978|
|Chronic kidney disease, n (%)||592 (4.3)||141 (5.1)||0.059|
|Coronary artery disease, n (%)||1397 (10.0)||280 (10.1)||0.975|
|Atrial fibrillation, n (%)||323 (2.3)||64 (2.3)||0.994|
|Valvular heart disease, n (%)||213 (1.5)||56 (2.0)||0.067|
|Systemic lupus erythematosus, n (%)||93 (0.7)||42 (1.5)||<0.0001|
|Rheumatoid arthritis, n (%)||206 (1.5)||80 (2.9)||<0.0001|
Figure 1 exhibits the results of Kaplan–Meier survival analysis, and psoriasis patients had a significantly higher risk of developing future ischemic stroke event. The crude hazard ratio of ischemic stroke for psoriasis was 1.25-times greater than that for controls (95% confidence interval [CI], 1.04–1.51; P = 0.016). After adjusting for the patients’ age, sex and all comorbidities, psoriasis was independently associated with a 27% increased risk of developing a future ischemic event (hazard ratio, 1.27; 95% CI, 1.05–1.52; P = 0.012).
The findings of our current study demonstrate that psoriasis is associated with future development of ischemic stroke. It provides one piece of the puzzle to complete the picture about the risk of stroke in psoriasis patients.
Psoriasis is a chronic inflammatory disease and characterized by dysregulation of T-cell response and pro-inflammatory cytokines.7 Upregulation of the pro-inflammatory cytokines are seen in both conditions of psoriasis and cardiovascular disease.8 Psoriasis patients also have increased baseline levels of C-reactive protein.9 All together, psoriasis may contribute to stroke risk through chronic inflammation and subclinical atherosclerosis. Additionally, adipose tissue contributes to the regulation of multiple metabolic pathways via adipokines, which also play a key role in the pathogenesis of cardiovascular disease. Adipokines might also serve as a missing link in the causal relationship between psoriasis, chronic inflammation and atherosclerosis.10
Previous population-based studies have reported the relationship between psoriasis and stroke risk in Western populations, and their results were inconsistent.3–5 Our study provides evidence that psoriasis also conferred an independent risk of ischemic stroke in patients of Asian ancestry.
There are some limitations in our study. First, psoriasis cases were defined as having a diagnostic code of psoriasis. Second, some patient information influencing risk of ischemic stroke like smoking and family history of stroke was lacking. Third, the diagnosis of stroke was based on the administrative claims data reported by physicians or hospitals. Finally, because the NHI program in Taiwan was initiated in 1995, the dataset used in the current study only allowed us to trace administrative claims from 1996–2007.
Our study concludes that new-onset psoriasis may be independently associated with an increased risk of future ischemic stroke development. Future studies might be arranged to confirm the effect of preventing stroke by treating psoriasis.