Angiotensin II type 1 receptor A1166C polymorphism in relation to incident cardiovascular events, hypertension, and blood pressure control in elderly Caucasians and African Americans
Objective: The C allele of the angiotensin II type 1 receptor (AT1R) A1166C polymorphism has been associated in several studies with increased risks of hypertension (HTN) and myocardial infarction (MI), and with enhanced blood pressure (BP) response to ACE inhibitors but not calcium antagonists. Most of these studies were small, and none included large numbers of African Americans. We examined these associations in the Cardiovascular Health Study, an observational cohort study of risk factors for coronary disease and stroke in men and women ≥ 65 years of age. Methods: All 771 self-identified African Americans plus 1333 randomly-selected Caucasians were genotyped for the AT1R polymorphism. BP, medication use, and HTN were assessed annually. Incident MI/coronary death (CHD, n = 125 in whites; n = 60 in blacks), incident total cardiovascular events (CVD, n = 226 in whites; n = 101 in blacks), incident congestive heart failure (CHF, n = 146 in whites; n = 55 in blacks), and incident HTN (n = 184 in whites; n = 85 in blacks) were identified during up to 8 years of follow-up. Results: Genotype frequency distributions differed between whites (AA 49%, AC 41%, CC 10%) and blacks (85%, 15%, 1%, p < 0.0005). Age, gender or HTN at baseline did not differ by genotype in either group. In both whites and blacks, genotype was not associated with incident CHD (HR for AC/CC vs. AA, 95% CI in whites = 1.0, 0.7-1.5; blacks, HR = 0.7, 0.3-1.5), incident total CVD events (whites, HR = 1.0, 0.8-1.3; blacks, HR = 0.9, 0.5-1.6), incident CHF (whites, HR = 1.1, 0.8-1.5; blacks, 0.6, 0.3-1.4) or newly-identified HTN (whites, HR = 0.8, 0.6-1.1; blacks, HR = 1.1, 0.6-1.9). Among treated hypertensives, the association of genotype with controlled BP (<140/<90) did not differ between users of calcium channel blockers and users of ACE inhibitors in either race. Conclusion: In this large population-based elderly cohort, the AT1R A1166C polymorphism was not associated with prevalent or newly-identified HTN, incident CVD events, or BP response to antihypertensive agents in either Caucasians or African Americans.