Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study

Abstract

Objective: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke.

Methods: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA.

Results: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]).

Conclusion: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.

Figure 1

Multivariable ischemic stroke risk (odds ratios and 95% confidence intervals on log scale) associated with rheumatoid arthritis (RA) treatment in a 6-month window before the index stroke, adjusted for Health Assessment Questionnaire score, total joint replacement, RA duration, and for low-dose aspirin and comorbidity index immediately prior to index observation. Numbers in parentheses represent the number of patients using that therapy (cases and controls). Analysis included 41 RA patients with ischemic stroke and 791 RA patients without ischemic stroke. Anti-TNF = anti–tumor necrosis factor.

Figure 2

Multivariable ischemic stroke risk (odds ratios and 95% confidence intervals) associated with baseline rheumatoid arthritis (RA) treatment, adjusted for Health Assessment Questionnaire score, total joint replacement, RA duration, and for low-dose aspirin and comorbidity index at baseline. Numbers in parentheses represent the number of patients using that therapy in cases and controls. Analysis included 41 RA patients with ischemic stroke and 791 RA patients without ischemic stroke. Anti-TNF = anti–tumor necrosis factor.