Influence of the angiotensin converting enzyme I/D gene polymorphisms on left ventricular diastolic filling in patients with essential hypertension

Background: An insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene accounts for 50% of the variance in serum ACE activity. ACE is responsible for the generation of angiotensin II, which not only has pressor and mitogenic activities but also exerts effects on left ventricular diastolic performance. Objective: To investigate the contribution of genetic polymorphisms at the ACE gene to the development of diastolic functional abnormalities in 100 patients with essential hypertension. Methods and results: The left ventricular mass (LVMI) of each patient was assessed echocardiographically. We calculated peak and integral early:late left ventricular diastolic filling ratios (E:A(p), and E:A(l), respectively) and determined the ACE genotype from leukocyte DNA. There was no significant difference in age, sex, blood pressure and LVMI among genotype groups. Analysis of covariance modelled for indices of diastolic function, adjusted for age, sex, heart rate and LVMI, demonstrated that the E:A(p) interacted with age (P < 0.0001), heart rate (P < 0.001) and ACE genotype (P = 0.018). Similarly, the E :A(l) interacted with age (P < 0.001), heart rate (P = 0.025) and ACE genotype (P = 0.047). There was a strong correlation between the E:A(p) and the LVMI for the DD group (r = -0.81, P < 0.0001) but not for the ID (r = -0.03, P = 0.83) and II (r = -0.23, P = 0.23) groups. Conclusions: These findings suggest that the I/D polymorphism of the ACE gene influences the relationship between left ventricular mass and echocardiographic left ventricular diastolic filling abnormalities in patients with essential hypertension.