BACKGROUND AND PURPOSE: Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. METHODS: The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. RESULTS: During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. CONCLUSIONS: In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke.

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 0.10). 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.

Background: Fibroblast growth factor-23 (FGF-23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated FGF-23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function. Methods and Results: A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990-1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF-23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow-up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF-23 was not associated with risk at < 40 pg/mL but was positively associated with risk at > 40 pg/mL. Compared with those with FGF-23 < 40 pg/mL, those in the highest FGF-23 category (≥58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function. Conclusions: High levels of serum FGF-23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population-based cohort. This association was independent of traditional cardiovascular risk factors and kidney function.