Novel Risk Factors and Prevention for Stroke

Abstract

Stroke is a major public health problem and is a leading cause of long-term disability. Identifying novel risk factors could potentially aid in understanding the mechanisms and pathophysiology of stroke. In addition, atrial fibrillation (AF) is a strong risk factor for stroke and there is a need to understand the risks associated with stroke prevention therapies. Using data from the Atherosclerosis Risk in Communities (ARIC) study, the first manuscript analyzed the cross-sectional association of atrial myopathy—characterized by abnormalities in left atrial (LA) function and size—and brain MRI markers of silent cerebrovascular disease. Several measures of lower LA function were associated with cerebral microbleeds and brain infarcts. In the second manuscript, we explored the relationship of 4,877 plasma proteins to risk of incident ischemic stroke in the ARIC study. Among the proteins that were identified in ARIC, three proteins were validated in an external cohort, the Cardiovascular Health Study. Mendelian randomization analysis suggested that NT-proBNP may be causally related to ischemic stroke. The third manuscript used data from the Medicare 20% sample to assess stroke prevention among patients with AF. The Watchman implant is a minimally invasive procedure for patients with AF who are at an elevated risk for stroke and have an oral anticoagulant contraindication. Compared to oral anticoagulant users, patients with the Watchman device did not have an increased risk of stroke or death. However, an increased risk for bleeding was noted, though this risk was more pronounced in the initial 180 days after the procedure. Collectively, this dissertation identifies novel risk factors for stroke that could contribute to future stroke prevention efforts and also assesses risks associated with current prevention therapies.