The Whitehall II study was set up to investigate the reasons for the social gradient in coronary heart disease, elucidating the contribution of psychosocial factors, health behaviors and their biological intermediaries. The internationally unique contribution of the Whitehall II study arises out of its combination of rich measures of work and non-work social positions and psychosocial factors coupled with detailed biological phenotyping, in an occupational cohort now moving out of work. If this renewal application is successful, this cohort of civil servants, men and women initially aged 35-55, will have been followed for 19-21 years. New findings from the last period of NHLBI support show that there is a social gradient in CHD morbidity and in the metabolic syndrome; the metabolic syndrome is associated with measures of automatic function and the hypothalamic-pituitary-adrenal axis; and in turn, aspects of these biological pathways are related to the psychosocial factors. Employment grade predicts the rate of decline in health functioning and continues to predict CHD mortality in participants who are beyond working age. Taken together these findings lead to the three specific aims of this application: (1) to determine the extent to which socio-economic position and psychosocial factors influence pathophysiological responses and sub-clinical vascular disease directly and via health related behaviors, (2) to examine psychosocial explanations for socio-economic differences in coronary health in an occupational cohort moving out of work, (3) to determine, in our aging population, the relationships between socio-economic position, coronary disease and health functioning and disability. NHLBI support is sought for key new measures at phase 7, continued follow up of the cohort, and for data analysis in support of our three specific aims.
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