ACE GENOTYPE, BP, AND EXERCISE TRAINING IN HYPERTENSIVES

高血压是心血管（CV）疾病的主要危险因素。许多基因位点的多态性变异影响一个人的血压（BP）和患高血压的风险。我们的初步数据表明，血管紧张素转换酶（ACE）基因型影响运动训练高血压患者的收缩压和舒张压降低。因此，在健康、久坐、中老年血压正常或1期高血压患者中，我们将验证我们的主要假设：ACE II和ID患者运动训练后的收缩压和舒张压降低程度高于ACE DD基因型患者。根据ACE基因型筛选后，受试者将稳定在AHA第一步饮食中。然后受试者完成基线测试、6个月的运动训练和最终测试。如果运动训练中不同基因型的VO2max、体成分或区域脂肪分布发生不同的变化，则将它们与初始血压和种族一起纳入模型，以评估运动训练中遗传和非遗传变量对血压变化的独立影响。探索性分析将确定肾素-血管紧张素系统成分的变化是否随运动训练在基因型组中有所不同。我们的初步数据还表明，载脂蛋白E （APO E）和脂蛋白脂肪酶（LPL） Pvull基因型影响高血压患者运动训练后的血压降低。因此，探索性分析将确定APO E3或E4型高血压患者的收缩压和舒张压是否比APO E2型高血压患者更容易在运动训练中降低，以及LPL Pvull +/+型高血压患者是否比LPL Pvull -/-或+/-型高血压患者更容易在运动训练中降低。与我们的假设相一致的结果将确定4000多万患有高正常血压或1期高血压的美国人，他们将通过运动训练获得最大的心血管疾病风险降低，从而使运动训练的最佳分层受益最大。相反，通过运动训练来确定哪些高血压患者会降低血压，将使他们能够专注于对他们更有效的干预措施。在未来，这些结果可能会与尚未确定的遗传标记一起用于药物和其他生活方式干预的最佳血压反应，以指导新诊断的高血压患者进行最有效的血压和心血管疾病风险控制干预。

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.