Although a growing body of evidence indicates strong links between psychological stress (stress) and untoward cardiovascular disease (CVD) outcomes, comprehensive examination of these effects remains lacking. The "Cumulative Psychological Stress and Cardiovascular Disease Risk in Middle Aged and Older Women" study is embedded within the landmark Women's Health Study (WHS) follow-up cohort and seeks to evaluate the individual and joint effects of stressors (cumulative stress) on incident CVD risk, including myocardial infarction, stroke, coronary revascularization and CVD death. GWAS data will be used for exploratory analyses to identify any genes associated with stress and CVD. This study prospectively follows 25,335 women (mean age 72.2 ± 6.04 years) without CVD who returned a short mailed stress questionnaire at baseline and 3 years of follow-up inquiring about their experiences with stress including perceived stress, work stress, work-family spillover, financial stress, traumatic and major life events, discrimination and neighborhood environment/stressors. Other domains ascertained were sleep, anger, cynical hostility, depression, anxiety, social support, intimate partner relations, and volunteer and social activities. Higher levels of cumulative stress were associated with younger age and black race/ethnicity, divorced or separated marital status, increased prevalence of obesity, smoking, diabetes, depression and anxiety (p<0.001 for each). Findings from this study will provide clinically important, new information about associations of cumulative stress, environmental, lifestyle and genetic factors with incident CVD risk in aging women