The natural history of hypertension among African-Americans is characterized by a more virulent course, a higher prevalence of target organ damage such as left ventricular hypertrophy (LVH), heart failure and renal failure. We postulate that this high risk group reflects a hypertensive phenotype in which a predisposition to LVH is associated with abnormalities in endothelial function that predispose to vasoconstriction and structural microvessel occlusion within the coronary circulation. Setting in motion a cascade of pathobiological processes that, predispose to myocardial ischemia, recurrent micro-infarctions, heart failure and eventual cardiac mortality. Specifically we will: 1) Define the relative contribution of ACE/ANGN/EC-NOS genotypes as determinants of brachial artery endothelial dysfunction and inducible myocardial ischemia in asymptomatic African-American hypertensives. 2) Assess the interrelationship between brachial artery endothelial function, coronary artery endothelial function and inducible myocardial ischemia in symptomatic African-American patients with hypertension. 3) Evaluate the efficacy of chronic treatment with angiotensin converting enzyme inhibitors in African-American hypertensives with baseline endothelial dysfunction and inducible myocardial ischemia.
These aims will be accomplished by performing non-invasive brachial artery studies of endothelial function in hypertensive patients and matched controls; using genetic markers to examine the contribution of angiotensin and nitric oxide balance in cardiac organ damage in hypertension. 4) Compare non-invasive stress test techniques to invasive measures of myocardial blood flow in hypertensive patients with chest pain. The outcome of this project is to identify potential genetic associations in the high risk hypertensive patients for early intervention and treatment.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRR1)
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Morehouse School of Medicine
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