VASCULAR STIFFNESS & CARDIOVASCULAR FUNCTION IN ELDERLY

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DESCRIPTION (adapted from the applicant's abstract): The long-term objectives of the proposed research are to understand the relationships among pulsatile arterial load, left ventricular (LV) mechano-energetic performance, and LV and vascular remodeling in the elderly. It has been hypothesized that increased arterial stiffness is causally linked to the genesis of isolated systolic hypertension (ISH) in elderly and may represent a cardiovascular risk factor. The specific aims of the proposal are to characterize: (1) the independent effects of arterial stiffness (both magnitude and distribution) on the mechanical performance of the coupled LV-arterial system and LV energetics; (2) the mechanical determinants of ISH and of increased arterial stiffness in elderly population with ISH; and (3) the temporal changes in arterial and LV mechanical properties in order to identify the cardiovascular initiating factor(s) for ISH. Hypotheses: (1) The pressure-overloaded heart is more sensitive to the changes in arterial stiffness, both from mechanical and energetic viewpoints; (2) Increased arterial stiffness is a necessary but not sufficient condition for ISH to occur; other cardiovascular factors must coexist; and (3) Increase in arterial stiffness, especially regional redistribution, precedes the occurrence of ISH. In the isolated rabbit heart preparation, mechano-energetic data will be acquired using both normal and pressure-overloaded hearts. Using noninvasive and invasive techniques, cardiovascular function will be evaluated in 150 African-American subjects divided into three groups (normal, combined systolic-diastolic hypertension, and ISH). Quantitative characterizations of the arterial system will include input impedance spectrum and regional pressure-diameter-pulse wave velocity relationships. LV size, shape, and mass and indices of contractility (chamber and myocardial) and oxygen consumption will be quantified. Two hundred subjects from a population with high incidence of hypertension (the Hutterites from South Dakota) will participate in a longitudinal study. Using noninvasive techniques, the longitudinal study will quantify the temporal changes in arterial and LV properties during the development of ISH.