Abstract 2824: Renin-Angiotensin-Aldosterone System Gene Polymorphisms Influence Alterations in Cardiac Hypertrophy During Long-Term Follow-Up in Hypertrophic Cardiomyopathy
Expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy (HCM) varies with renin-angiotensin-aldosterone system (RAAS) gene polymorphisms. To test our hypothesis that RAAS gene polymorphisms influence the alterations in cardiac hypertrophy in patients with HCM during long-term follow-up, the following RAAS gene polymorphisms were assessed in 115 HCM patients (68 M, 47 F): ACE I/D, AT1 receptor A/C1166, AT2 receptor A/C3123 and aldosterone synthase C-344T. Patients were followed at our outpatient clinic between 1994 and 2005 and underwent regular 2D- echocardiography. LV end-diastolic diameter, LV outflow tract (LVOT) gradient at rest, interventricular septum (IVS) - and LV posterior wall thickness were measured. LV mass (LVM) and Wigle score were calculated according to approved formulas. Patients with a follow-up of <2 years (n=23) or who underwent septal myectomy (n=15) were excluded from analysis. Mean(±SEM) follow-up in the remaining patients was 7.8±0.3 years. IVS (22.4±0.6 vs. 19.2±0.5 mm), Wigle score (6.6±0.3 vs. 3.9±0.2) and LVOT gradient (37.7±4.3 vs. 14.4±2.3 mm Hg) all decreased (P<0.001) over time, whereas LVM (327±12 vs. 321±12 g) remained unaltered. However, LVM increased by 38±24 g in subjects with the ACE DD genotype, as compared to a decrease by 22±15 g in ACE I allele carriers (P<0.05). Furthermore, LVM decreased to a larger degree in women with the AT2 receptor AA genotype as compared to women with the AT2 receptor C allele (−106±43 vs. −14±16 g; P<0.02). ΔLVM did not associate with the AT1 receptor or the aldosterone synthase genotype. Multiple regression analysis showed that ΔLVOT (β=+1.2), the ACE D allele (β=+51.2), and the AT2 receptor A allele (β=−48.4) were significant predictors of the change in LVM, independently of age, sex, plasma renin, AT1 receptors or aldosterone synthase. In conclusion, the ACE D allele and AT2 receptor A allele are significant predictors of the change in LVM during follow-up of HCM patients. Our data support the concept of ACE-dependent angiotensin II generation contributing to cardiac hypertrophy in HCM. They simultaneously suggest that AT2 receptor stimulation exerts antiproliferative effects in the heart. This warrants the application of AT1 receptor antagonists in HCM.