Association of polymorphism of the endothelial NO synthase gene (NOS3–786T>C) with severity of left ventricle diastolic dysfunction and pulmonary hypertension in patients with heart failure and preserved ejection fraction

Abstract

The aim – to determine polymorphisms of the nitric oxide synthase gene -786T>C rs 2070744 and the association of the corresponding genotypes with the severity of left ventricle (LV) diastolic dysfunction (DD), pulmonary hypertension (PH) and elastic properties of the arteries in patients with arterial hypertension (AH) and heart failure (HF) with preserved ejection fraction (EF).
Materials and methods. We included 69 patients (pts) with AH and HF with preserved EF (31 female (41.9 %) and 33 male (58.1 %)), aged 67.4±10.2 years; II–III class NYHA, hemodynamically stable. According to Shah’s criteria, the «aging» phenotype was identified in 11 (15.9 %) pts, «obesity» – 14 (20.3 %) pts, «coronary artery disease» – 16 (23.2 %) pts, «pulmonary hypertension» – 17 (24.6 %) pts (with a significant predominance of patients with CC genotype), «arterial hypertension» – 17 (24.6 %) pts.
Results and discussion. «Wild» homozygous TT genotype was found in 34 pts (49.3 %, TT group), heterozygous TC genotype – in 21 pts (30.4 %, TC group) and «mutant» homozygous CC genotype – in 14 pts (20.3 %, CC group). The groups did not differ in gender (male 19 or 55.9 %, 12 or 60 % and 11 or 61.1 %, p<0.05) and average age (67.1±8.9, 65.4±10.6 and 64.9±10.3 years p>0.05), and in prevalence of comorbidities. The worst result of 6-minute walk test was in the CC group compared with TT and TC (371.8±77.7, 385.7±85.4 and 314.3±69.1, p<0.05), as well as higher NT-proBNP level (668.1±317.8, 636.9±433.2 and 806.9±369.7, p<0.05), greater LVMI (187.4±37.1, 182.2±25.7 and 195.2±28.5, p<0.05). There was markedly more pronounced DD LV in the CC group compared with TT and TC, according to average e’ (p<0.05) and E/e’ (p<0.05). SPAP was the highest in the CC group (p<0.05), as well as PCWP and TPG (p<0.05). Patients of the CC group had worse elastic properties of arteries according to AIx75 (p<0.001) and PWVc-f (p<0.05), with a decrease in SAC (by 38.2 and 29 % compared to TT and TC (p<0.05) and an increase in Ea, respectively, by 21 and 9 % (p<0.05). According to the cuff test in patients of the CC group, compared with those in the TT and TC groups, worsening of endotelium-dependent vasodilation, respectively by 19.8 and 17.3 % (p<0.05) was revealed.
Conclusions. Compared to other polymorphisms, the CC genotype of the NOS3 rs 2070744 gene is associated with greater severity of DD LV, LH and impaired LV diastolic function and elastic properties of systemic arteries, according to pulse wave analysis in patients with AH and HF with preserved EF.