Ankylosing Spondylitis Linked to Cardiovascular Mortality

Janis C. Kelly

August 11, 2015

Ankylosing spondylitis (AS) is the latest inflammatory arthritis to be associated with increased risk for vascular mortality. The nearly 50% increase in risk is so significant that experts call for comprehensive screening and treatment of modifiable risk factors in all patients with AS.

Nisha Nigil Haroon, MD, DM, DNB, from Toronto Western Hospital, Ontario, Canada, and colleagues published the population-based retrospective cohort study online August 11 in Annals of Internal Medicine.

Senior author Nigil Haroon, MD, PhD, DM, assistant professor of rheumatology and medicine, University of Toronto, and clinician scientist and staff rheumatologist, Toronto Western Hospital, told Medscape Medical News that the major clinical implication of the study is that patients with AS should be screened and closely monitored for the prevention, early diagnosis, and treatment of cardiac and coronary events.

"Recent evidence suggests that patients with AS have increased risk of vascular disease such as coronary heart disease. Our study not only strengthens this data but also provides new information that mortality after a vascular event is higher in AS patients. Further, our results suggest that vascular mortality is directly linked to AS (as comorbidities were controlled for)," Dr Haroon said.

Large Cohort Reveals Strong Link

The researchers used administrative health data from four core data sets — the Ontario Health Insurance Plan (OHIP) Registered Persons Database, the OHIP Claims History Database, the Canadian Institute for Health Information Discharge Abstract Database, and the Ontario Registrar General Death Database — to identify a study cohort of 21,473 patients with AS age 15 or older (mean age, 45.66 years). They excluded patients with baseline coronary artery disease or cerebrovascular disease. Patients were compared to 86,606 persons without AS who were matched for age, sex, and location of residence.

With a follow-up of 166,920 patient-years in the AS cohort and 686,461 patient-years in the comparator group, the researchers found that patients with AS had a 43% (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.19 - 1.72) higher risk for vascular mortality, a 60% (HR, 1.60; 95% CI, 1.17 - 2.20) higher risk for cerebrovascular mortality, and a 35% (HR, 1.35; 95% CI, 1.07 to 1.70) higher risk for cardiovascular mortality than comparators. The vascular death rate was 50% (HR, 1.50; 95% CI, 1.17 - 1.91) higher for men with AS and 34% (HR, 1.34; 95% CI, 1.01- 1.79) higher for women with AS than their matched comparators.

The risk for vascular mortality remained 36% (HR, 1.36; 95% CI, 1.13 - 1.65) higher in patients with AS after adjustment for baseline comorbidities, including cancer, diabetes mellitus, dementia, inflammatory bowel disease, peripheral vascular disease, hypertension, and chronic kidney disease. However, sex-based subanalyses showed that the increased risk was seen only in men (HR, 1.46; 95% CI, 1.13 - 1.87).

Independent predictors of vascular death in patients with AS were age, sex, income, dementia, and peripheral vascular disease.

"The risk for vascular mortality increased by 12% with each year of advancing age. Compared with women, men had almost double the risk for vascular mortality," the authors write. Vascular mortality was not associated with baseline diabetes, chronic kidney disease, inflammatory bowel disease, cancer, or ethnicity.

Dr Haroon said, "We were surprised by the finding that AS patients had 60% higher risk of cerebrovascular mortality…. This was calculated based on deaths occurring in people who have suffered strokes and symptomatic transient ischemic attacks and those undergoing carotid revascularization. Another concerning finding is that in our subgroup analysis among seniors with AS (aged 66 and above) most vascular medications except statins did not reduce the risk of mortality."

The researchers found a 10% decrease in mortality risk in patients with AS associated with use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) (HR, 0.1 [CI, 0.01 - 0.61]; P = .01) and a 25% reduced risk associated with use of statins (HR, 0.25 [95% CI, 0.13 - 0.51]; P < .001).

Dr Haroon said, "The decrease in risk with NSAID use may come as a surprise to the readers. We generally consider NSAIDs to increase risk of vascular events. A previous study in RA [rheumatoid arthritis] showed the same. Hence, in inflammatory disease, anti-inflammatories may protect patients from vascular death. However, it should be borne in mind that this might be a reflection of NSAIDs being used in the elderly population with lowest risk of vascular events."

Dr Haroon concluded, "[Randomized controlled trials] assessing the effect of vascular protective medications such as statins and antihypertensives in AS are warranted. Large multicenter trials should assess whether TNF [tumor necrosis factor] inhibitors are preventing or delaying the onset of vascular disease in AS."

Data Are Convincing

Inger Jorid Berg, MD, Department of Rheumatology, Diakonhjemmet Hospital and Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Norway, who was not involved in the study, told Medscape Medical News, "This is a very interesting and well-performed large population study providing new information on cardiovascular disease (CVD) mortality in ankylosing spondylitis. I think the data from Haroon and colleagues are especially convincing as they have a large sample size, in addition to results being in line with previous findings of increased mortality and CVD morbidity in patients with AS."

Dr Berg noted that study provides some information on risk factors of vascular mortality but lacks information about the contribution of traditional CVD risk factors and physical activity, a limitation the authors acknowledged.

Dr Berg added, "The finding of increased vascular mortality in AS highlight that clinicians, both rheumatologists and general practitioners, should put effort into identifying AS patients with increased risk of CVD. It is important to perform regular assessment of the traditional CVD risk factors and initiate treatment when indicated. Furthermore, inflammation may be an important mediator of the increased risk of CVD, and optimal treatment of the disease activity might be of importance, although data to support this are limited."

Dr Haroon reported grants from the Arthritis Society; nonfinancial support from the Institute of Clinical Evaluative Sciences; grants from Toronto General and Western Hospital Foundation during the conduct of the study; and personal fees from AbbVie, Amgen, Celgene, Janssen, UCB, and Hospira outside the submitted work. The other authors and Dr Berg have disclosed no relevant financial relationships.

Ann Intern Med. Published online August 11, 2015. Abstract

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