African Americans (AA) women have among the greatest risk for the development of various cardiovascular diseases (CVD) relative to any other ethnic population including Caucasians (CA). For example the rate of hypertension in AA women above the age of 20 is ~46% vs. ~30% in CA women and the prevalence of all types of CVD in AA women is approximately ~48% compared to ~32% in CA women and approximately 540,000 AA women die from CVD in the United States each year. The involved mechanisms of elevated disease risk are multifactorial; however, impaired macro and microvascular function and heightened vasoconstrictor responsiveness to sympathetic nerve activity (sympathetic vascular transduction) are likely contributing factors. Our preliminary data demonstrates blunted macro and microvascular responsiveness in AA women indicating impaired vascular function. Furthermore, we recently demonstrated that sympathetic vascular transduction is also heightened in AA men relative to CA men. Our preliminary data in AA women along with evidence of elevated ?1-adrenergic receptor sensitivity provides support in this population. The long-term goal of the PI is to better understand mechanisms underlying cardiovascular pathology in populations with elevated disease risk. The short-term goal is to systematically assess mechanisms of impaired macro and microvascular function and elevated sympathetic vascular transduction in AA women, a population with the highest risk for CVD.
Specific aim 1 will build upon our preliminary data and expand the findings in a larger sample size (vascular function data) as well as extend the work in to the female population (sympathetic vascular transduction data). Specifically, this aim will characterize impairments in macro and microvascular function in the peripheral circulation using non- invasive techniques. It is hypothesized that macro and microvascular function will be impaired in AAs relative to CA.
In Aim 1 we will also test the hypothesis that AA women have heightened sympathetic vascular transduction relative to CA women.
Specific aim 2 is designed to systematically assess mechanisms of vascular dysfunction and elevated sympathetic vascular transduction in AA women. To accomplish this Aim we will utilize the minimally invasive technique of intradermal microdialysis to locally administer vasoactive substances into the cutaneous circulation which will allow for assessment of mechanisms involved in impaired vasodilation / augmented vasoconstriction. Taken together this approach will provide important mechanistic insight into greater prevalence of cardiovascular and metabolic disease in AA women. Ultimately this work will go a long way in providing important information to inform future strategies to combat elevated disease risk in this population.
African Americans women are an understudied population despite having among highest risk for and incidence of cardiovascular disease (CVD) relative to other populations including Caucasian American (CA) men and women. The aims outlined in this proposal are designed to provide systemic and mechanistic insight for potential reasons resulting in elevated CVD disease risk in this population. Specifically, findings from this proposal will provide valuable insight into mechanisms of altered neural and vascular control in AA with the ultimate goal of identifying therapeutic strategies to minimize this disease risk.
