ABSTRACT: BACKGROUND AND PURPOSE:This study investigated chronic stress, depressive symptoms, anger, and hostility in relation to incident stroke and transient ischemic attacks in middle-aged and older adults. METHODS:Data were from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort study of 6749 adults, aged 45 to 84 years and free of clinical cardiovascular disease at baseline, conducted at 6 US sites. Chronic stress, depressive symptoms, trait anger, and hostility were assessed with standard questionnaires. The primary outcome was clinically adjudicated incident stroke or transient ischemic attacks during a median follow-up of 8.5 years. RESULTS:One hundred ninety-five incident events (147 strokes; 48 transient ischemic attacks) occurred during follow-up. A gradient of increasing risk was observed for depressive symptoms, chronic stress, and hostility (all P for trend ?0.02) but not for trait anger (P>0.10). Hazard ratios (HRs) and 95% confidence intervals indicated significantly elevated risk for the highest-scoring relative to the lowest-scoring group for depressive symptoms (HR, 1.86; 95% confidence interval, 1.16-2.96), chronic stress (HR, 1.59; 95% confidence interval, 1.11-2.27), and hostility (HR, 2.22; 95% confidence interval, 1.29-3.81) adjusting for age, demographics, and site. HRs were attenuated but remained significant in risk factor-adjusted models. Associations were similar in models limited to stroke and in secondary analyses using time-varying variables. CONCLUSIONS:Higher levels of stress, hostility, and depressive symptoms are associated with significantly increased risk of incident stroke or transient ischemic attacks in middle-aged and older adults. Associations are not explained by known stroke risk factors.