Association of renin-angiotensin-aldosterone system gene polymorphisms with left ventricular hypertrophy in patients with heart failure with preserved ejection fraction: A case-control study

Background: Heart failure with preserved ejection fraction (HFpEF) has close ties with hypertension, though risk factors to the development of HFpEF in hypertensive patients are not fully understood. Left ventricular hypertrophy (LVH) signifies the susceptibility toward diastolic heart dysfunction, and genetic determinants of LVH as a result may serve as risk predictors for HFpEF in hypertension. We investigated the role of three renin-angiotensin-aldosterone system (RAAS) gene polymorphisms in the development of LVH in hypertensive patients with a diagnosis of HFpEF. Methods: A total of 176 hypertensive patients with a diagnosis of HFpEF were divided to cases with LVH and controls without. rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of angiotensin receptor type 1 were genotyped using PCR-RFLP method. Results: Genotypes and allele frequencies were significantly different between the case and control groups for rs4343 and rs4291, whereas no difference was observed for rs5186.Conclusion: Increased ACE activity explains the significant association of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore, findings support the pathophysiologic links between RAAS and increased LV mass in hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms may serve as risk predictors of HFpEF in hypertensive patients.