Downloaded from http://ard.bmj.com/ on March 9, 2016 - Published by group.bmj.com ARD Online First, published on October 22, 2015 as 10.1136/annrheumdis-2015-207980 Basic and translational research EXTENDED REPORT Incidence and predictors for cardiovascular events in patients with psoriatic arthritis Lihi Eder,1 Ying Wu,2 Vinod Chandran,1 Richard Cook,2 Dafna D Gladman1 Handling editor Tore K Kvien ABSTRACT myocardial infarction (MI) and stroke was higher in 1Centre for Prognosis Studies Objective To assess the incidence and risk factors of patients with PsA who were not using disease- in the Rheumatic Diseases, cardiovascular events in patients with psoriatic arthritis modifying antirheumatic drugs (DMARDs) and was Toronto Western Hospital, (PsA). similar to that in patients with psoriasis and Toronto, Ontario, Canada Methods A cohort analysis was conducted involving rheumatoid arthritis (RA). 2Department of Statistics and Actuarial Science, University of patients recruited and followed over the period from The increased cardiovascular morbidity in psoriatic Waterloo, Waterloo, Ontario, 1978 to 2013 in a large PsA clinic. The participants disease may be partially attributed to the high preva- Canada were assessed at 6 to 12-month intervals according to a lence of obesity-related metabolic abnormalities, such standard protocol. The collected information included as impaired glucose tolerance and atherogenic lipid Correspondence to fi 611 Dr Dafna D Gladman, Psoriatic demographics, lifestyle habits, medical history, pro le, in addition to unhealthy lifestyle habits Arthritis Program, Centre for medications use and PsA-related outcomes. The primary (eg, smoking, physical inactivity) that are common in Prognosis Studies in the outcome was a composite major cardiovascular end these patients. Moreover, the effect of certain medica- Rheumatic Diseases, Toronto point comprising myocardial infarction, ischaemic stroke, tions used for psoriasis and arthritis, including non- Western Research Institute, revascularisation or cardiovascular death. The association steroidal anti-inflammatory drugs (NSAIDs) and aci- University Health Network, 399 Bathurst Street 1E-410B, between the features of disease activity and the tretin, may also have a deleterious effect on the vascu- Toronto, Ontario, occurrence of cardiovascular events was assessed using lature system. These factors may act synergistically Canada M5T 2S8; Cox proportional hazard models. with systemic inflammation to promote atherogenesis. [email protected] Results A total of 1091 patients with PsA were While the independent effect of disease-related fl Received 26 May 2015 analysed. During the follow-up period, 104 in ammation on cardiovascular risk is established Revised 22 September 2015 cardiovascular events occurred. A considerable in RA, few studies have thus far attempted to eluci- Accepted 26 September 2015 proportion of patients developed a cardiovascular event date the link between metabolic abnormalities and (19.8% of the patients by the age of 70 years and PsA-related factors to determine the independent 30.1% of patient by the age of 80 years). No trend in effect of psoriatic disease activity on cardiovascular the risk of developing cardiovascular events was morbidity. Several studies found an association observed over the decades from 1978 to 2013 between the extent of inflammation and surrogate (p=0.73). In multivariate analysis, the following end points of cardiovascular outcomes. This associ- variables were independent predictors of major ation was independent of traditional cardiovascular cardiovascular events: hypertension (relative risk (RR) risk, supporting the notion that PsA is a risk factor – 1.81, p=0.015), diabetes (RR 2.72, p<0.001) and the for cardiovascular morbidity.12 14 number of dactylitic digits (RR 1.20, p<0.001). In this cohort study we aimed (1) to estimate the Sedimentation rate was a significant predictor only cumulative incidence of cardiovascular events in among women (RR 1.83, p=0.02). patients with PsA and (2) to identify independent Conclusion A significant proportion of patients with predictors for developing cardiovascular events in PsA develop cardiovascular events during the course of these patients. their disease. Increased cardiovascular risk is associated with a combination of traditional cardiovascular risk METHODS factors and disease activity. Patients and setting A cohort analysis was conducted in patients fol- lowed from 1978 to 2013 at the University of INTRODUCTION Toronto PsA clinic. Patients attending the clinic are Psoriasis is an immune-mediated skin disease affect- enrolled in an ongoing prospective study aimed at ing 2%–3% of the population.1 Psoriatic arthritis assessing prognostic factors in PsA. Each patient is (PsA) is an inflammatory arthritis that affects assessed at 6–12-month intervals according to a 14%–30% of people with psoriasis, and can lead to standard protocol.15 Information collected significant joint damage and disability.23Recent and stored in a database includes demographics, literature highlighted the increased cardiovascular lifestyle habits, medical history, medication use, – risk in patients with psoriatic disease.4 6 disease-related outcomes and laboratory findings. A recent meta-analysis found that patients with The majority (98%) of the patients in the clinic psoriasis have 40% increased risk of developing met the ClASsification of Psoriatic ARthritis To cite: Eder L, Wu Y, cardiovascular diseases.7 Although the information (CASPAR) criteria for classification of PsA.16 Chandran V, et al. Ann Rheum Dis Published Online about cardiovascular risk in PsA is limited com- Patients who developed a cardiovascular event First: [please include Day pared with that in psoriasis, several studies showed prior to the diagnosis of PsA were excluded from Month Year] doi:10.1136/ a similar trend.89Ogdie et al10 reported that the the study. All subjects’ written consent was annrheumdis-2015-207980 risk of developing major cardiovascular events, obtained according to the Declaration of Helsinki. Eder L, et al. Ann Rheum Dis 2015;0:1–7. doi:10.1136/annrheumdis-2015-207980 1 Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& EULAR) under licence. Downloaded from http://ard.bmj.com/ on March 9, 2016 - Published by group.bmj.com Basic and translational research The study has been approved by the University Health Network whether there was a trend with age in the risk of cardiovascular Ethics Board. events, treating non-cardiovascular death as a competing risk. Non-parametric estimates of the cumulative incidence function Data collection and definitions for the composite cardiovascular event were obtained, again The clinic database was searched to identify patients who devel- treating non-cardiovascular death as a competing risk and the oped cardiovascular events. Each identified event was then eval- age at study entry as a left-truncation time since events were uated by reviewing data from hospital admissions, death only modelled after study entry. certificates and medical records from relevant specialists. Two Multivariate Cox proportional hazard models were fitted for physicians (LE, DDG) discussed equivocal events and reached a the age at the occurrence of the primary and secondary compos- consensus designation regarding the diagnosis. The primary ite cardiovascular event with time-dependent explanatory vari- composite end point occurred at the time of the first major car- ables. The dates that cardiovascular risk factors changed were diovascular event with components including MI, ischaemic obtained from patient records when available; if laboratory mea- stroke, revascularisation or cardiovascular death. MI was surements were not available at a particular visit, the last defined as one of the following: definite electrocardiographic abnormalities; typical symptoms with probable electrocardio- graphic abnormalities and abnormal enzymes; typical symptoms and abnormal enzymes. Revascularisation was defined as any of Table 1 Characteristics of the study population at clinic entry the following procedures: coronary bypass surgery, coronary Age 43.8±12.8 angioplasty with or without stent insertion and carotid endarter- Sex: male (%) 612 (56.1) ectomy. A secondary composite end point was the first cardio- vascular event, including major cardiovascular events as defined Duration of psoriasis (years) 15.17±12.38 above, angina, transient ischaemic accident (TIA) and congestive Duration of PsA (years) 5.65±7.95 heart failure (CHF). Angina pectoris was defined as chest dis- Hypertension (%) 220 (20.2) comfort that was aggravated by physical activity and relieved by High triglycerides (%) 197 (22) rest or by the use of nitroglycerine and confirmed by a cardiolo- High cholesterol (%) 365 (40.6) gist or abnormal findings on myocardial perfusion study or angi- Diabetes (%) 59 (5.5) ography. CHF was defined based on typical symptoms and signs Smoking-ever (%) 408 (44) on physical examination, abnormal chest X-ray or abnormal PASI fi fi nding on echocardiogram. Ischaemic stroke was de ned as <10 (%) 619 (83.5) sudden onset of focal neurological deficit lasting more than 24 h 10–19 (%) 77 (10.4) and attributable to a focal vascular cause. The definition of TIA >19 (%) 45 (6.1) was the same as stroke but the neurological deficit resolved within 24 h. Tender joint count 0 (%) 205 (18.8) Predictors of cardiovascular events 1–7 (%) 512 (46.9) Both traditional cardiovascular risk factors and PsA-related vari- >7