Coronary heart disease (CHD) and hypertension have been associated with the insulin metabolic syndrome (insulin resistance, hyperinsulinemia, central obesity, dyslipidemia, hemostatic abnormalities, elevated resting blood pressure and increased sympathetic activity) and also alterations in cardiac structure and adrenoceptor sensitivity. Since the literature suggests that blood pressure reactivity to the cold pressor test is a predictor of future hypertension, we hypothesize that subjects who are hyper-reactive to this stressful behavioral challenge will display evidence of abnormalities in insulin metabolism, cardiac structure and adrenoceptor function reflecting heightened cardiovascular risk when compared with normo-reactive subjects. This project will examine 280 (of 425 reactivity screened) normotensive individuals incorporated into a 2 (hyper-reactor, normo-reactor) X 2 (African-American, White American) X2 (women, men) design./ The major aim of the project is to measure as a function of reactivity status, ethnicity and gender, indices of insulin metabolism (insulin resistance using the euglycemia-insulin clamp, glucose tolerance using the oral glucose tolerance test), central fat deposition (waist-to- hip girth), lipid metabolism (triglycerides, HDL, LDL), hemostatic function (plasminogen activator inhibitor 1), hemodynamic function (blood pressure, cardiac output, total peripheral resistance), autonomic function (plasma catecholamines, systolic time intervals, heart rate variability), cardiac structure (left ventricular mass and wall thickness using echocardiography) and adrenoceptor and baroreceptor sensitivity (using beta- and alpha- receptor agonist infusions). To the extent that differences between reactor groups are observed on these measures, it is of interest to examine further whether groups differences exist in the underlying mechanisms mediating the blood pressure response to stressful challenge. Therefore, this project will also examine whether two behavioral stressors that have been observed to primarily evoke cardiac changes (mental arithmetic) or induce vasomotor changes (cold pressor) will distinguish differences in hemodynamic and autonomic response among hyper-reactive and normo-reactive subjects.
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