Ventricular Vascular Coupling: Correlates and Prognosis

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DESCRIPTION (provided by applicant): Progressive left ventricular (LV) remodeling is a fundamental substrate of heart failure (CHF). Alterations in LV and vascular remodeling (VVR) with age, i.e., a stiffer heart ejecting into a noncompliant vascular tree, predispose to CHF, especially diastolic CHF. Prior studies indicate sex differences in LV remodeling, vascular stiffness and diastolic dysfunction. We propose to assess VVR and diastolic function via concurrent echocardiography (echo) and arterial tonometry in 3500 participants of the Framingham Heart Study (FHS) Offspring and Omni cohorts. We will test 4 major hypotheses: 1. Sex differences in arterial stiffness contribute to dissimilarities in LV mass, geometry, and systolic function in women vs. men, and to the greater female susceptibility to diastolic CHF. 2. Environmental and genetic factors influence LV diastolic function, 3. Environmental and genetic factors determine longitudinal changes in vascular stiffness and LV measurements. 4. Individuals with accelerated LV and vascular aging have greater propensity for developing HTN, CHF and vascular events (CVD). Our specific aims are to examine: 1) the cross-sectional relations between vascular stiffness measures and LV remodeling; 2) the environmental and genetic correlates of LV diastolic function indexes; 3) the environmental and genetic factors determine longitudinal changes in vascular stiffness, and LV remodeling; and 4) the relations of measures of VVR, diastolic function, and longitudinal changes in LV and vascular stiffness measures to the incidence of HTN, CHF, and CVD. The FHS is uniquely suited for this proposal because it provides a large, single site, community-based sample of middle-age to older men and women with extensive antecedent risk factor data. The forthcoming examination cycle is ideal to perform vascular testing and echo because the aging participants are experiencing marked increases in vascular stiffness, LV diastolic dysfunction, and CHF risk. LV and vascular stiffness measures at prior examinations facilitate the evaluation of longitudinal changes and associated risk.