Hypertension is a major risk factor for cardiovascular (CV) disease. Polymorphic variations at numerous gene loci affect a person's blood pressure (BP) and risk of developing hypertension. Our preliminary data suggest that angiotensin converting enzyme (ACE) gentoype affects the systolic and diastolic BP reductions that occur in hypertensives with exercise training. Thus, in healthy, sedentary, middle-aged and older subjects with High Normal BP or Stage 1 Hypertension, we will test our primary hypothesis: Systolic and diastolic BP decrease more with exercise training in ACE II and ID than in ACE DD genotype individuals. After screening based on ACE genotype, subjects will be stabilized on an AHA Step I diet. Subjects then complete Baseline Testing, 6 months of exercise training and Final Testing. If VO2max, body composition, or regional fat distribution change differently among genotypes with exercise training, they will be included, with initial BP and race, in models to assess the independent effects of genetic and non- genetic variables on BP changes with exercise training. Exploratory analyses will determine if changes in renin- angiotensin system components change differently with exercise training among genotype groups. Our preliminary data also indicate that apolipoprotein E (APO E) and lipoprotein lipase (LPL) Pvull genotype affect BP reductions with exercise training in hypertensives. Thus, exploratory analyses will determine if systolic and diastolic BP decrease more with exercise training in APO E3 or E4 than APO E2 hypertensives and more in LPL Pvull +/+ than LPL Pvull -/- or +/- genotype hypertensives. Results consistent with our hypothesis will identify those of the 40 plus million Americans with high normal BP or Stage 1 hypertension who will obtain the greatest CV disease risk reductions with exercise training, resulting in the optimal stratifying of exercise training to those benefiting the most. Conversely, identifying hypertensives who will reduce BP the lease with exercise training would allow them to focus on interventions that might be more efficacious for them. In the future, these results may be used along with yet-to-be-identified genetic markers for optimal BP responses to medications and other lifestyle interventions to direct newly-diagnosed hypertensives to their most efficacious intervention for BP and CV disease risk control.
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