Association of a renin genetic polymorphism with left ventricular mass regression in hypertensive patients treated with aliskiren, losartan, or both

Abstract

Background: Left ventricular hypertrophy (LVH) as a consequence of hypertension is associated with a higher risk for cardiovascular events, and blocking the renin-angiotensin-aldosterone system (RAAS) has been associated with LVH regression. We hypothesized that genetic polymorphisms of renin (REN) and the angiotensin-1 receptor (AT1), may impact the individual end-organ response to RAAS inhibition on LV mass regression. Methods: We studied hypertensive patients from the Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial (n=233; mean age 58 (plus or minus)10 yrs, 75% male, BMI 31.4, baseline BP 150.7/15.5/91.8 (plus or minus) 9.4 mm Hg) with left ventricular hypertrophy and a body mass index (BMI) > 25 kg/m2, randomized to aliskiren 300mg, losartan 100mg, or their combination daily for 36 weeks. LV mass was assessed at baseline and follow-up with cardiac magnetic resonance imaging. Genotyping for REN -5312C/T and AT1 (rs5182 and rs275651 ) variants was performed with Taqman(registered trademark) and sequencing assays. Results: Baseline characteristics, LV mass and degree of blood pressure lowering did not differ by genotype. Allele frequencies did not differ by treatment group, and were in Hardy-Weinberg equilibrium. REN -5312 T allele carriers (28%) exhibited less LV mass reduction overall compared to the CC genotype (72%) ((Delta) -3.5g/m2 versus -7.1g/m2, p=0.036), greatest in those receiving combination therapy ( -2.1g/m2 versus -9.9g/m2, p=0.009), even adjusting for degree of systolic blood pressure lowering (p=0.01). Patients in the CC group receiving combination therapy also demonstrated greater percent reduction in plasma aldosterone compared to T allele carriers (-29% versus +11%, p = 0.019). There were no associations noted between AT1 variants and LV mass regression. Conclusions: Patients with hypertension and LV hypertrophy with the REN-5312 CC genotype may be more responsive to RAAS blockade on LV mass regression, which may in part be due to more pronounced reduction in plasma aldosterone.