We will study multiple clinical and biochemical characteristics of siblings with essential hypertension in order to subclassify their blood pressure (BP) disorder into one of the already described (or possibly newly emerging) intermediate phenotypes of this disease. Clinical markers will include: the presence of obesity, abdominal adiposity, early onset and excessive severity of hypertension and most importantly, sodium sensitivity of blood pressure. The latter will be studied with an established inpatient protocol of sodium loading and sodium deprivation. Biochemical and hormonal markers will include: blood levels of insulin, renin, aldosterone, catecholamines, vasopressin and lipids, platelet membrane alpha2-adrenergic receptors, and urinary kallikrein excretion rates. Characterization of phenotypes in these hypertensives has two major purposes: 1. In hypertensive patients of all ethnic and racial backgrounds, intermediate phenotype data and genomic DNA will be provided to a core center located at Boston University, in a collaboration that has the purpose of identifying the genes involved in the causation of essential hypertension and 2. In hypertensive patients of Hispanic American background, definition of intermediate phenotypes will serve to fill a major vacuum in the understanding of the pathophysiology of hypertension in this ethnic group. The hypothesis underlying our second purpose, based on our preliminary observations on Caribbean Hispanics of the New York area, is that hypertension of Hispanic Americans will exhibit one major phenotype, characterized by high prevalence of sodium sensitivity, low-renin status, and perhaps low kallikrein excretion and high vasopressin. Another possible phenotype in Hispanics, supported by epidemiologic evidence on concomitant illnesses in southwestern and southcentral Mexican-Americans, is the clustering of obesity, evidence for insulin resistance (with or without diabetes) and hyperlipidemia. Our expectation is that characterization of the phenotypes of hypertension in Hispanic subjects will facilitate future clinical research necessary to devise recommendations for the tailoring of antihypertensive therapy in this ethnic minority, analogous to what has already been realized for hypertensives of African-American origin.
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