EVOLUTION OF CARDIOVASCULAR RISK WITH NORMAL AGING

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DESCRIPTION (provided by applicant): The cardiovascular (C-V) system is a vital organ system most affected by the aging process. The natural history of C-V aging in terms of arterial and cardiac structure/function (C-V indices) is governed by a complex interplay between an intrinsic (biologic) aging effect and a burden of C-V risk factors beginning early in life. This renewal application focuses on the pathobiological traits associated with C-V aging in a community-based, black-white, middle-aged cohort having been followed over 30 years beginning in childhood. The specific aims are to 1) continue monitoring the progression of C-V indices with respect to chronological age, the burden of C-V risk factor variables and familial traits of C-V risk and longevity; 2) determine the relationship between changes in C-V indices and biological aging ascertained by chromosomal telomere dynamics; 3) examine the influence of birth weight on the burden of C-V risk factor variables since childhood and the rate of adverse changes in C-V indices. The ongoing study cohort followed during the previous grant period (Cohort I, n=1,200) and an additional cohort examined as children 10 years ago (Cohort II, n=1,200) are available to achieve these aims. In addition to telomere dynamics, birth weight, and subclinical C-V indices, data on selected key variables relevant to C-V aging, in particular risk variables of metabolic syndrome including inflammation and oxidative stress will be collected. Both cohorts will be examined for 1) C-V indices by carotid IMT, left ventricular structure and function, brachial artery compliance, and arterial pulse wave velocity; 2) C-V risk factor variables comprising obesity measures, blood pressure, lipoprotein variables, glucose, insulin, and parameters of oxidative stress; and 3) telomere length. In addition, data on birth weight, adiponectin, insulin like growth factor-I and binding proteins, homocysteine, fibrinogen, plasminogen activator inhibitor-I, C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 will be obtained in Cohort I; telomere attrition rate from childhood to adulthood and familial traits of C-V risk and longevity in Cohort I1. The extensive serial database of the Bogalusa Heart Study provides unique and valuable resources. Findings from the proposed research will further the understanding of C-V aging and predisposing factors that influence aging in a bi-racial young to middle age population. Observations derived from this research will help develop effective preventive strategies to temper mediators that influence premature C-V morbidity and mortality.