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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Objective

To determine whether the presence of psoriatic arthritis (PsA) is associated with greater comorbidity, in particular cardiovascular morbidity, compared to psoriasis without arthritis.

Methods

Six hundred eleven patients with PsA were recruited from the University of Toronto Psoriatic Arthritis Clinic and 449 psoriasis without arthritis patients were recruited from the University of Toronto Psoriasis Cohort. The clinical database was used to identify the prevalence of cardiovascular and other comorbidities in both PsA and psoriasis without arthritis patients. Univariate and multivariate logistic regression analyses were conducted to estimate odds ratios (ORs), comparing the odds of ever having a given comorbid disease in PsA patients with those in psoriasis without arthritis patients. Covariates included age, sex, education, smoking status, severity and duration of psoriasis, medication status, and other comorbidities.

Results

The prevalence of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and at least 1 cardiovascular event in PsA patients was 37.1%, 30.0%, 20.7%, 12.0%, and 8.2%, respectively. This was significantly higher than in psoriasis without arthritis patients, with unadjusted ORs ranging from 1.54 to 2.59. In the multivariate analyses, hypertension remained significantly elevated (adjusted OR 2.17). PsA was also significantly associated with infections not treated with antibiotics (presumably viral), neurologic conditions, gastrointestinal disorders, and liver disease (adjusted ORs 2.83, 4.76, 21.53, and 7.74, respectively). Infections treated with antibiotics and depression/anxiety were relatively common in PsA, with a prevalence of 30.5% and 20.7%, respectively. However, this was not significantly different from psoriasis without arthritis after multivariate adjustments.

Conclusion

The results suggest that inflammatory joint disease may play a role in both cardiovascular and noncardiovascular morbidity in PsA.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematosus plaques on body surfaces. The estimated prevalence is 1.5% to 3.0% of the population in North America and Europe, but occurs less frequently elsewhere (1, 2). There is increasing recognition that the manifestations of psoriasis extend beyond the skin. Studies have shown associations between psoriasis and other systemic diseases, including Crohn's disease, obesity, diabetes mellitus, depression, and cancer (3). Most recently, a relationship between psoriasis and increased risk of myocardial infarction, cerebrovascular disease, and peripheral vascular (cardiovascular) disease has been reported (3–5). The observed excess risk appears to be greatest in younger patients and those with more severe psoriasis. It has been suggested that this elevated risk reflects an increased prevalence of conventional cardiovascular risk factors (smoking, hypertension, diabetes mellitus, dyslipidemia, and obesity) in psoriasis patients, in conjunction with nonconventional risk factors unique to chronic inflammatory psoriasis, for instance, fibrinogen, C-reactive protein, and homocysteine (6). However, systemic inflammatory joint disease is a potentially important confounder in the study of psoriasis patients (6–8). It is estimated that 6% to 42% of patients with psoriasis develop psoriatic arthritis (PsA), and there is evidence to suggest that PsA, similar to rheumatoid arthritis and other inflammatory joint diseases, is associated with an increased risk of cardiovascular morbidity and mortality (9–12).

Clearly the associations between psoriasis, PsA, cardiovascular disease, and other comorbidities are complex and not well understood due to limited data. To our knowledge, only 2 studies (13, 14) have compared comorbidity in patients with psoriasis alone to that in patients with PsA. The study by Ciocon et al (13) compared the prevalence of hypertension, hypercholesterolemia, coronary artery disease, diabetes mellitus, colitis, and Crohn's disease between the 2 groups and found no significant differences. Since this study was based on a survey, patients' diagnoses were not confirmed either for psoriasis without arthritis or PsA. By contrast, Christophers et al (14) reported that patients with confirmed PsA were significantly more likely to have hypertension or upper gastrointestinal tract problems than confirmed psoriasis without arthritis patients, after adjusting for age and sex. Elevated cholesterol, depression, renal impairment, and type 2 diabetes mellitus occurred more often in PsA patients, but did not reach statistical significance. Unfortunately, neither study measured and adjusted for the severity of inflammatory skin and joint disease, nor controlled for the potential confounding influence of immunosuppressant medications such as methotrexate, cyclosporine, leflunomide, and azathioprine. Evidence suggests that such treatments themselves are associated with the development of cardiovascular disease and malignancy (15, 16). On the other hand, anti–tumor necrosis factor agents may actually protect patients from cardiovascular morbidity (17, 18). A better understanding of the associations between psoriasis, PsA, and comorbidities can help in the management of chronic inflammatory skin and joint disease, and most importantly, minimize the comorbid complications and improve patient outcomes (19).

The main purpose of this study was to determine whether the presence of PsA is associated with greater comorbidity, in particular cardiovascular morbidity, compared to psoriasis without arthritis. A secondary objective was to describe the pattern of comorbidity in PsA patients.

Significance & Innovations

  • This is the first study that compares well-phenotyped patients with psoriasis without arthritis and patients with psoriatic arthritis with regard to comorbidities.

  • The study demonstrates that patients with psoriatic arthritis are more prone to cardiovascular comorbidity than patients with psoriasis without arthritis.

  • Patients with psoriatic arthritis also have a higher prevalence of neurologic, liver, and gastrointestinal comorbidities.

  • Taken together, the results suggest that inflammatory arthritis may be contributing above and beyond psoriasis.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Patient population.

Psoriasis patients.

Psoriasis without arthritis patients were recruited from the University of Toronto Psoriasis Cohort, which enrolls psoriasis patients uncomplicated with arthritis and aims to study risk factors for PsA. To minimize selection bias, psoriasis patients were recruited from several sources, including dermatology clinics at Toronto Western Hospital, community-based dermatologists, family medicine clinics in Toronto, and the general public in the greater Toronto area by advertising in local newspapers. All of the patients were assessed by a rheumatologist initially to rule out the presence of inflammatory arthritis, and then annually for signs or symptoms of inflammatory arthritis. If inflammatory arthritis was diagnosed, the patient was considered to have developed PsA and was censored, thereby ensuring that all of the patients in the psoriasis cohort were free of arthritis (20).

PsA patients.

PsA patients were recruited from the University of Toronto Psoriatic Arthritis Clinic. This cohort consisted of patients referred for the management of PsA. The clinic serves as primary, secondary, and tertiary referral centers, with a broad spectrum of disease activity and illness duration. Similar to the psoriasis cohort, patients were recruited from several sources, including the psoriasis education and research center and both community-based and hospital-based dermatologists, rheumatologists, general internists, and general practitioners in the greater Toronto area. At the initial visit to the PsA clinic, other forms of arthritis were ruled out. Patients are reevaluated at 6–12-month intervals (21).

Assessments.

For both the University of Toronto Psoriasis Cohort and the University of Toronto Psoriatic Arthritis Clinic, a standard protocol was completed at each visit by clinic physicians and data were entered into a computerized database. Each assessment consisted of a detailed medical history, physical examination, and laboratory evaluation, including items related to psoriasis with and without arthritis as well as current or past medication history, comorbidities, and known risk factors. In this study we included only psoriasis without arthritis and PsA patients who had at least 1 clinic visit since 2006. This ensured that clinical assessment procedures and data collection were the same in both cohorts. In addition, we used data from the first visit since 2006.

Measures.

Comorbid conditions.

The Functional Comorbidity Index (FCI) (22), an 18-item list of diagnoses (Table 1), was modified as a basis for selecting medical comorbidities for analysis. The main modifications included the exclusion of arthritis, and due to insufficient information, peripheral vascular disease, hearing impairment, and visual impairment. To reflect current literature on comorbidities in psoriasis without arthritis, PsA, and other chronic inflammatory rheumatic diseases (1, 3, 18, 22–26), we also determined the occurrence of hyperlipidemia and hypertension, cancer, autoimmune disorders, liver disease, and infections. The clinical database was used to identify comorbid conditions in both psoriasis without arthritis and PsA patients. Comorbid conditions were recorded in the database as reported by patients at the clinic visit, protocol physical examination, and use of agents to treat comorbid condition (e.g., antidepressants, anxiolytics, and lipid-lowering drugs). Additional information was also sought from the patient charts, hospital records, pathology, laboratory or radiography reports, and primary care physicians (9, 26).

Table 1. Modified Functional Comorbidity Index (22)
Osteoporosis
Asthma
Chronic obstructive pulmonary disorder, acute respiratory distress syndrome
Angina
Congestive heart failure
Myocardial infarction
Neurologic disease
Stroke or transient ischemic attack
Types 1 and 2 diabetes mellitus
Upper gastrointestinal disease
Depression
Anxiety
Degenerative disc disease
Obesity
Demographic and clinical variables.

Conventional risk factors for comorbidity included age, sex, daily alcohol use, and smoking. Other risk factors relating to disease severity were age at onset (psoriasis without arthritis and PsA), disease duration (psoriasis without arthritis and PsA), past and current medications, number of clinically damaged joints, Psoriasis Area and Severity Index (PASI) score (27), and body surface area (BSA) affected by psoriasis (28).

Statistical analyses.

Descriptive statistics were used to compare sociodemographic and illness characteristics between PsA and psoriasis without arthritis patients. To compare morbidity between the 2 patient groups, we first calculated the modified FCI (mFCI) score, a summary count of the 14 comorbidities identified in Table 1. Linear regression models were used to compare mFCI scores between PsA and psoriasis without arthritis, adjusting for age, sex, and psoriasis duration. Univariate and multivariate logistic regression models were used to estimate odds ratios (ORs) that compared the odds of ever having a particular comorbid condition (e.g., cardiovascular disease) in PsA patients with those in psoriasis without arthritis patients. For these logistic analyses, the total number of PsA (psoriasis without arthritis) patients with the particular comorbidity was derived. This count reflected the number of patients with at least 1 of the diagnoses included within the particular disease category (see below for details). Multivariate logistic analyses adjusted for the following covariates: age, sex, psoriasis duration, current smoking status, PASI, medication status, and other comorbid conditions.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Included in the study were 611 PsA patients and 449 psoriasis without arthritis patients (Table 2). The majority of the patients were white (87% in the PsA group and 76% in the psoriasis without arthritis group). As shown in Table 2, men comprised approximately 58% of both groups. PsA patients were significantly older than psoriasis patients (mean age 50 years versus 46.5 years) and experienced a longer psoriasis duration (mean duration 22.2 years versus 16.3 years). A substantial proportion of both groups obtained university education. PsA patients were more likely to be overweight than psoriasis without arthritis patients, but less likely to smoke and drink alcohol. There was no difference in psoriasis severity (as measured by the BSA and PASI) between the 2 groups, with approximately 13% of both PsA and psoriasis without arthritis patients having a history of severe psoriasis. In the PsA patients, the mean number of actively inflamed joints and clinically damaged joints (9.3 and 13.2, respectively) reflected moderate to severe disease activity and damage. PsA patients were more likely to have “ever” received nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), including methotrexate, and biologic agents than psoriasis without arthritis patients, but less likely to have taken ultraviolet therapy and topicals for psoriasis. The mean ± SD mFCI score in PsA and psoriasis without arthritis patients was 1.4 ± 1.4 (range 0–7) and 0.68 ± 0.88 (range 0–6), respectively, indicating that PsA patients on average had more comorbid conditions (at least those identified in Table 1), even after adjusting for major covariates (age, sex, psoriasis duration, current smoking status, PASI score, and medication status [P = 0.005]).

Table 2. Sociodemographic and clinical characteristics of patients at the first clinic visit since 2006*
 PsA (n = 611)Psoriasis without arthritis (n = 449)P
  • *

    PsA = psoriatic arthritis; BMI = body mass index; PASI = Psoriasis Area and Severity Index; BSA = body surface area; NSAIDs = nonsteroidal antiinflammatory drugs; DMARDs = disease-modifying antirheumatic drugs; mFCI = modified Functional Comorbidity Index.

Men, %58.3057.500.7933
Age, mean ± SD years50.3 ± 13.246.5 ± 13.1< 0.0001
College or university education, %67.965.30.0402
Duration of psoriasis, mean ± SD years22.2 ± 13.416.3 ± 14.2< 0.0001
Duration of PsA, mean ± SD years13.8 ± 11.1
Current smokers, %12.0024.40.0001
Current daily drinkers, %7.1010.40.058
BMI, mean ± SD kg/m229.2 ± 6.427.9 ± 5.50.0013
PASI, mean ± SD5.0 ± 7.75.8 ± 6.00.0793
Severe PASI (>10), %12.8013.40.7724
BSA, mean ± SD10.8 ± 19.410.0 ± 12.60.7336
No. of actively inflamed joints, mean ± SD9.3 ± 9.8
No. of swollen joints, mean ± SD4.4 ± 5.0
No. of damaged joints, mean ± SD13.2 ± 14.2
Severe clinical damage (≥5), %63.1
NSAIDs ever used, %84.403.300.0001
DMARDs ever used, %73.4010.200.0001
Methotrexate ever used, %60.3042.900.0167
Biologic agents ever used, %25.403.300.0001
Ultraviolet therapy ever used, %26.6081.700.0001
Topicals for psoriasis, %82.8092.000.0001
mFCI score, mean ± SD1.47 ± 1.410.68 ± 0.88< 0.0001

Prevalence of cardiovascular comorbidities in PsA.

The most prevalent comorbid condition in PsA patients was hypertension (Table 3). Overall, 226 patients had this condition, corresponding to a prevalence of 37.1%. The prevalence of obesity, hyperlipidemia, and type 2 diabetes mellitus was 30.0%, 20.7%, and 12.0%, respectively. Fifty patients had at least 1 cardiovascular event (myocardial infarct, n = 29; angina, n = 29; cardiomyopathy, n = 2; congestive heart failure, n = 4; and cerebrovascular disease, n = 6), corresponding to a prevalence of 8.2%. In the univariate analyses, the prevalence of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and at least 1 cardiovascular event was significantly greater in PsA patients than in psoriasis without arthritis patients, with unadjusted ORs ranging from 1.54 to 2.59 (Table 3).

Table 3. Prevalence of comorbidities among patients with PsA compared with that in patients with psoriasis without arthritis*
 PsA, no. (%)Psoriasis without arthritis, no. (%)Unadjusted OR (95% CI)PMultivariate adjusted OR (95% CI)Multivariate adjusted OR (95% CI)
  • *

    PsA = psoriatic arthritis; OR = odds ratio; 95% CI = 95% confidence interval; BMI = body mass index.

  • Multivariate adjusted model included for age, sex, education, psoriasis duration, current smoking status, Psoriasis Area and Severity Index score, biologics, methotrexate, and nonsteroidal antiinflammatory drugs for cardiovascular disease, hypertension, and gastrointestinal disease only.

  • Multivariate adjusted model included for same variables as above, plus other comorbid conditions.

  • §

    Angina, myocardial infarction, cardiomyopathy, congestive heart failure, and cerebrovascular accident.

  • P < 0.05.

  • #

    Asthma, chronic obstructive lung disease, and sleep apnea.

  • **

    Ulcer and irritable bowel syndrome.

  • ††

    Neuropathy, seizure disorder, and multiple sclerosis.

  • ‡‡

    Thyroid disease, celiac disease, type 1 diabetes mellitus, Sjögren's syndrome, and systemic lupus erythematosus.

  • §§

    Fatty liver and hepatitis.

Cardiovascular disease§50 (8.2)15 (3.3)2.59 (1.43–4.67)0.00160.79 (0.19–3.18)1.42 (0.40–5.03)
Hypertension226 (37.1)88 (19.6)2.42 (1.82–3.22)< 0.00012.08 (1.02–4.25)2.17 (1.22–3.83)
Hyperlipidemia126 (20.7)65 (14.5)1.54 (1.11–2.14)0.01011.01 (0.60–1.71)0.76 (0.38–1.51)
Type 2 diabetes mellitus73 (12.0)30 (6.7)1.90 (1.22–2.96)0.00451.80 (0.91–3.57)2.03 (0.85–4.81)
Obesity (BMI ≥30 kg/m2)183 (30.0)119 (26.5)1.58 (1.19–2.09)0.00161.40 (0.92–2.12)1.29 (0.82–2.04)
Respiratory disease#68 (11.2)31 (6.9)1.69 (1.09–2.64)< 0.00011.18 (0.63–2.22)1.02 (0.50–2.08)
Gastrointestinal disease**44 (7.2)2 (0.5)17.41 (4.20–72.19)< 0.00013.38 (0.25–45.86)21.53 (1.61–287.89)
Neurologic disorder††51 (8.4)12 (2.7)6.75 (2.87–13.87)< 0.00014.06 (1.26–13.10)4.76 (1.12–19.40)
Autoimmune disease‡‡55 (9.0)38 (8.5)1.07 (0.69–1.65)0.76280.64 (0.33–1.23)0.49 (0.21–1.11)
Liver disease§§17 (2.9)5 (1.2)2.45 (0.90–6.69)0.08088.07 (1.61–40.56)7.74 (1.35–44.29)
Depression/anxiety126 (20.7)41 (9.3)2.60 (1.78–3.78)< 0.00011.85 (1.05–3.25)1.15 (0.58–2.29)
Cancer56 (9.2)20 (4.5)2.17 (1.28–3.67)0.00391.48 (0.67–3.27)1.58 (0.61–4.13)
Osteoporosis21 (3.5)13 (2.9)1.61 (0.58–2.35)0.67730.56 (0.18–1.70)0.71 (0.22–2.35)
Infections      
 None341 (55.9)312 (69.5)ReferentReferentReferentReferent
 Infection without antibiotic  treatment83 (13.6)29 (6.5)2.58 (1.32–5.02)0.00542.58 (1.32–5.02)2.83 (1.23–6.52)
 Infection with antibiotic  treatment186 (30.5)108 (24.0)1.12 (0.74–1.71)0.58761.12 (0.74–1.71)1.04 (0.63–1.71)

The results of the multivariate analyses indicated that the prevalence of hypertension remained significantly greater in PsA, after adjusting for age, sex, psoriasis duration, current smoking status, education, PASI, ever use of methotrexate, ever use of NSAIDs, ever use of biologic agents, and other comorbid conditions. In both multivariate models, the odds of having hypertension in PsA were approximately twice that in psoriasis without arthritis (Table 3). There was no evidence of significant differences in the odds of obesity, hyperlipidemia, type 2 diabetes mellitus, and at least 1 cardiovascular event between the 2 patient groups, once adjusting for covariates and other comorbidities. Similar results were obtained when adjusting for pack-years along with current smoking status, covariates, and other comorbidities, and when using body mass index (BMI) as a continuous measure in place of a categorical measure (BMI ≥30 kg/m2 = obese, BMI <30 kg/m2 = not obese).

Prevalence of other comorbidities in PsA.

The other most prevalent comorbidities were treated infections (30.5%), anxiety and depressive disorders (20.7%), and infections not treated with antibiotics (presumably viral; 13.6%). In addition, 68 patients had at least 1 or more respiratory illness (asthma, n = 51; sleep apnea, n = 13; and chronic obstructive lung disease, n = 1), corresponding to a prevalence of 11%. The prevalence of each of the remaining comorbidities was less than 10%. Fifty-five patients (9%) had at least 1 autoimmune disorder (thyroid disease, n = 50; celiac disease, n = 2; type 1 diabetes mellitus, n = 2; lupus, n = 3; and Sjögren's syndrome, n = 1). Fifty-six (9.2%) reported a history of cancer, 51 (8.4%) had at least 1 neurologic condition (neuropathy, n = 45; seizure disorder, n = 5; multiple sclerosis, n = 2), and 44 (7.2%) had at least 1 gastrointestinal disorder (ulcer, n = 36; irritable bowel syndrome, n = 12). The least prevalent conditions were osteoporosis (3.5%) and liver disease (2.9%; hepatitis, 1.5% and fatty liver, 1.4%).

The results of the multivariate logistic analyses indicated that PsA patients were significantly more likely to have a neurologic condition, infection not treated with antibiotics, liver disease, and gastrointestinal disorders compared with psoriasis without arthritis patients. Again, similar results were obtained when adjusting for pack-years along with current smoking status, covariates, and other comorbidities, and when using BMI as a continuous measure in place of a categorical measure of obesity.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Studies have shown an increased risk of cardiovascular morbidity in psoriasis and PsA. However, the majority of these studies have been conducted in psoriasis patients who have not been assessed for inflammatory arthritis. Consequently, the relative role of inflammatory joint disease in explaining the increased risk of cardiovascular disease in patients with psoriasis with and without arthritis remains unclear. To clarify the association between psoriasis, PsA, and cardiovascular disease, we examined whether PsA, an inflammatory joint and skin disease, was associated with a higher prevalence of cardiovascular morbidity compared with psoriasis without arthritis, after adjusting for conventional cardiovascular risk factors, medications, and psoriasis severity. The University of Toronto Psoriasis Clinic and Psoriatic Arthritis Clinic provided a unique opportunity to conduct this study. All of the patients were assessed by both a dermatologist and rheumatologist to confirm diagnosis of psoriasis with or without arthritis. They also underwent the same standard protocol; ensuring information on comorbidity was collected in the same manner, thereby minimizing detection and information bias (29).

The results of our study indicate that the leading comorbid condition in PsA was hypertension, with an estimated prevalence of 37%. This fell within the range of 25% to 49% reported in past PsA studies (10–12), but was higher than expected in the Canadian general population (30). Further, the prevalence of hypertension was significantly greater in PsA patients than in psoriasis without arthritis patients, even after adjusting for conventional cardiovascular risk factors, psoriasis duration and severity, medication history (ever use of NSAIDs, methotrexate, and biologic agents), and other comorbid conditions, including diabetes mellitus, obesity, and hyperlipidemia (adjusted ORs 2.08 and 2.17). This finding suggests that the additive burden of chronic inflammatory joint disease may account for the increased prevalence of hypertension seen in PsA compared with psoriasis without arthritis patients. The reason for this is unclear. However, patients with other inflammatory joint diseases such as RA and systemic lupus erythematosus also demonstrate higher rates of hypertension. Whether this reflects the effect of the inflammatory process on the vasculature is unknown. Other conventional cardiovascular risk factors were also prevalent in PsA, with 30.0%, 20.7%, and 12.0% of patients having obesity, hyperlipidemia, and type 2 diabetes mellitus, respectively. Although higher than in the Ontario general population (31, 32), these estimated prevalence rates were in the range of those reported by other PsA studies (10–14), with the exception of our relatively high obesity estimate. The prevalence of obesity, hyperlipidemia, and diabetes mellitus was higher in PsA patients than in psoriasis without arthritis patients, but did not reach statistical significance in the multivariate analyses, possibly due to insufficient power. The prevalence of at least 1 cardiovascular event in PsA patients was 8.2%, significantly higher than in psoriasis without arthritis patients (3.3%). Again this difference became nonsignificant in the multivariate analyses, possibly due to the small number of events, especially in the psoriasis group (i.e., lack of power). Overall, these results provide some tentative support for the role of inflammatory arthritis in cardiovascular morbidity in psoriasis patients with arthritis. Future studies will need to have larger sample sizes of both psoriasis without arthritis and PsA patients to ensure sufficient power to adequately control for the effects of cardiovascular risk factors, psoriasis severity, medication history, and other comorbid conditions.

A secondary objective of our study was to describe the pattern of comorbidity in PsA. As suggested in the literature, our results showed that depression and anxiety were prevalent comorbidities. The prevalence of depression and anxiety was 20.7%, significantly higher than in psoriasis without arthritis patients (9.3%) and higher than expected in the general population (33). This has potentially important clinical implications since depression has been shown to be associated with cardiovascular morbidity (34). This association may, in fact, help explain why the prevalence of depression/anxiety was no longer significantly different from psoriasis without arthritis patients, after adjusting for other comorbidities, including cardiovascular risk factors and events. Depression and anxiety are also known to influence treatment adherence, health behaviors, and perceived health (34). In addition, approximately 31% of the PsA patients reported having an infection that required treatment with an antibiotic. A recent study from the UK demonstrated that infection was an important cause of death among patients with severe psoriasis (35). Whether this is related to the inflammatory process or to immunosuppression from medications is unclear. Infections that were not treated with antibiotics were more common among patients with PsA. These are likely to be viral infections, and may be increased among patients with PsA due to the use of DMARDs.

Another noteworthy finding relates to the prevalence of at least 1 autoimmune disorder (defined as thyroid disease, celiac disease, type 1 diabetes mellitus, systemic lupus erythematosus, and Sjögren's syndrome). There has been some suggestion that the burden of autoimmune disorders may differ in PsA and psoriasis without arthritis patients (36). We found that the prevalence of at least 1 autoimmune disorder was 9% in both patient groups, with thyroid disease being the major condition. The prevalence of cancer in PsA patients was also 9% and significantly higher than that in patients with psoriasis without arthritis (4.5%). However, this difference did not remain statistically significant in the multivariate analyses. In a previous study we found no evidence to suggest that there is a higher risk of malignancy in our PsA clinic patients than in the general Ontario population (26). The prevalence of neurologic conditions (primarily neuropathies) was 9%. This was significantly greater than in psoriasis without arthritis and may be related to peripheral neuropathy due to diabetes mellitus, as well as carpal tunnel syndrome due to synovitis in the wrist joints. Gastrointestinal and liver disorders were less prevalent, at 7.2% and 3%, respectively, but were significantly more prevalent than in psoriasis without arthritis patients, even after adjusting for covariates, including NSAIDs, methotrexate, and biologics. However, the elevated prevalence of gastrointestinal and liver disease in PsA should be interpreted with considerable caution due to the relatively small number of patients with gastrointestinal and liver disorders, especially among psoriasis patients.

In addition, there are other methodologic issues that warrant further consideration. Our study patients may not be representative of patients with PsA and psoriasis without arthritis. To address this issue, we compared sociodemographic characteristics, disease features, and comorbidities in our PsA and psoriasis without arthritis patients to others reported in the literature (10–14, 37) and found they were quite similar, although our patients achieved a higher level of education. In addition, the range of comorbidities that was studied was not exhaustive. However, to our knowledge this was the first study to provide prevalence data on the majority of comorbidities linked to psoriasis without arthritis and PsA in the current literature. Furthermore, to disentangle the role of inflammatory joint and skin activity in cardiovascular comorbidity, our comparison group was comprised of psoriasis patients. Therefore, we were unable to assess whether the prevalence of previously unreported comorbid conditions (e.g., thyroid disease and asthma) in PsA was higher than expected in the general population. Where possible, we used external data to compare our prevalence data with those from general population samples. Finally, because this is a prevalence study, we cannot determine whether the individual comorbid conditions (e.g., obesity, hypertension) antedated the onset of psoriasis and PsA, or are a consequence of the disorders. This limits the ability of this study to speak to the inflammatory burden hypothesis.

The primary purpose of this study was to investigate the role of systemic inflammatory joint disease in cardiovascular morbidity in PsA by comparing the prevalence of cardiovascular risk factors and events in psoriasis patients with and without arthritis. Overall, the results provide some tentative support for the role of inflammatory arthritis in cardiovascular morbidity in PsA patients. The strongest evidence was an increased prevalence of hypertension in PsA patients compared to psoriasis patients, even after adjusting for medication status, psoriasis severity, and other comorbidities such as diabetes mellitus and obesity. There was also evidence to suggest an increased prevalence of neurologic conditions, infections, liver disease, and gastrointestinal disease in PsA patients. These results extend the current research related to overall comorbidity in PsA and may help in the clinical management of PsA patients.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Gladman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Husted, Thavaneswaran, Chandran, Eder, Rosen, Cook, Gladman.

Acquisition of data. Chandran, Eder, Rosen, Gladman.

Analysis and interpretation of data. Husted, Thavaneswaran, Chandran, Eder, Rosen, Cook, Gladman.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES