Increased Risk of Ischemic Stroke in Systemic Sclerosis: A National Cohort Study of US Veterans

Objective. Previously thought to involve primarily the microvasculature, systemic sclerosis (SSc) has been increasingly linked to macrovascular disease. Cardiovascular (CV) and cerebrovascular disease are responsible for 20-30% of mortality in SSc, but few studies have shown an independent association between SSc and stroke. We assessed whether SSc was an independent risk factor for ischemic stroke. Methods. We conducted a retrospective cohort study using the national Veterans Affairs (VA) administrative database containing records from 1999 to 2014. We obtained data for all patients with a diagnosis of SSc as well as 2 controls per SSc patient matched on sex, race, smoking status, and VA site. All patients were followed until development of ischemic stroke, death, or last encounter. We used a Cox proportional hazard regression model to estimate risk of ischemic stroke, with adjustments for CV comorbidities (hypertension, diabetes, atrial fibrillation, non-cerebrovascular atherosclerotic disease, hyperlipidemia), baseline medication use (aspirin, nonsteroidal antiinflammatory drugs), and Medicare enrollment. Results. Among 4545 individuals with SSc (83% male, mean age 60.9 yrs), the incidence rate of ischemic stroke was 15.3 per 1000 person-years (vs 12.2 in the control cohort), with an unadjusted HR 1.28 (95% CI 1.11-1.47). The adjusted HR was 1.21 (95% CI 1.05-1.40) after adjusting for baseline CV risk factors, medications, and Medicare enrollment. Conclusion. SSc is independently associated with a higher risk of ischemic stroke among US veterans. Patients with SSc represent a population likely to benefit from targeted stroke screening or prevention therapies.