Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study

Objectives To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Design Case control study. Setting An Iranian referral university hospital. Participants 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. Results The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. Conclusions In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart9s diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease.