We have little understanding of how the epidemiology of cardiovascular disease (CVD) and the value of CVD risk factors may evolve with aging in the HIV-infected population. Now that HIV has become a lifelong condition with the advent of effective antiretroviral therapy, this is of great concern. If risk factors for CVD are to be applied for cliical risk stratification in a evidence- based fashion, better data are needed across the age spectrum. The overarching goal of this proposal is to study how determinants of CVD change with aging among HIV-infected persons. Prior cohort studies, by applying similar research approaches to many cohorts across the age spectrum, have revealed much about the influence of age on the epidemiology of CVD. As has long been recognized, not only does CVD risk increase with aging, but the risk factors for CVD differ across early and later life. For example, while elevated cholesterol is unquestionably a causal CVD risk factor, in older adult's serum cholesterol levels have a weak, inconsistent relationship with incident and prevalent CVD. Elevated blood pressure (BP) and C-reactive protein, also known CVD risk factors, likewise are profoundly age-dependent. These phenomena have not been studied in the HIV-infected patient population. We plan an R21 proposal that will significantly extend and build upon the NHLBI HIV-CVD Consortium, which includes 9 R01 investigations on atherosclerotic CVD in adults and children with HIV. Coordination is provided by a Data Coordinating Center (DCC), Central Laboratory, and 3 specialized Reading Centers that have measured CVD risk factors, blood biomarkers, and noninvasive vascular images in identical fashion in the Consortium's nearly 5,000 enrolled subjects. Scientific aims will involve the identification of risk factors, including standard clinial CVD risk factors such as lipids, blood pressure and diabetes, as well as novel biomarkers of inflammation and hemostasis that are associated with the presence of subclinical atherosclerosis in patient groups across the lifespan from adolescence, through young-to- middle adulthood and later decades of adulthood.
Infection with HIV has become less likely to lead directly to death due to improvements in anti-retroviral therapy, but this improvement has resulted in an increase in cardiovascular events among HIV-infected patients. There has not previously been a careful study using cohort data with the potential to look at how this increase in cardiovascular risk varies based on age at HIV infection. By grouping together many of the premier cohorts in the HIV world, we hope to shed light on the sub-clinical changes in cardiovascular risk and how these changes influence cardiovascular risk across the life-span.
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