The association between rheumatoid arthritis and stroke risk by serologic status and stroke subtypes

Background: Rheumatoid arthritis (RA) has been associated with an increased stroke risk, but associations by serostatus (seropositive RA (SPRA) vs seronegative RA (SNRA)) and with subtypes of stroke (ischemic stroke (IS) or hemorrhagic stroke (HS)) are not well established. In addition, it is not well-known whether the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) are associated with altered stroke risk. Methods: This nationwide cohort study used the Korean National Health Insurance Service database and included participants who were first diagnosed with RA in the period 2010–2017 with no previous history of stroke, and who had a health checkup within 2 years before the index date (45,175 RA patients). They were compared (1:3 ratio) with non-RA controls matched by age and sex (135,525 non-RA controls). Results: Patients with RA had a significantly higher risk of both IS (adjusted hazard ratio (aHR) = 1.47, 95% confidence interval (CI) = 1.36–1.58) and HS (aHR = 1.31, 95% CI = 1.15–1.50) compared to controls. SPRA patients showed higher risk for both IS (aHR = 1.56, 95% CI = 1.43–1.69 SPRA vs aHR = 1.23, 1.08–1.41 SNRA) and HS (aHR = 1.40, 95% CI = 1.21–1.62 SPRA vs aHR = 1.09, 95% CI = 0.86–1.38 SNRA). No difference in stroke risk was observed between bDMARDs users and non-users (aHR = 1.66 for users, aHR = 1.41 for non-users). However, potential differences were noted with tsDMARDs use (aHR = 0.81 for users vs aHR = 1.43 for non-users), although not statistically significant. Conclusion: Patients with RA are at significantly greater risk for both IS and HS compared to those without RA, and SPRA patients showed higher risk than SNRA patients. Further studies are required to determine the potential of tsDMARDs in the prevention of stroke in RA.