Effect of combination antihypertensive therapy, including renin-angiotensin-aldosterone system inhibitors, on oxidative stress and arterial remodeling in hypertensive patients with heart failure with preserved ejection fraction

Abstract

Aim. To study the effect of triple combination therapy on oxidative stress and arterial remodeling in hypertensive patients with heart failure with preserved ejection fraction (HFpEF). Material and methods. The study involved 76 people with diagnosed HFpEF. After a comprehensive examination, patients were randomized into two equal groups: first group — patients who received perindopril 10 mg, indapamide 2,5 mg and amlodipine 5 mg; second — patients who received losartan 100 mg, indapamide 2,5 mg, amlodipine 5 mg. Before and 16 weeks after the therapy initiation, cardiac ultrasound, assessment of endothelial function with estimating endothelium-dependent vasodilation, assessment of vascular stiffness by photoplethysmography and compression oscillometry were carried out. The plasma concentration of oxidative stress marker 8-isoprostane was studied. Results. During the follow-up period, a significant improvement in endothelial function was noted: in the first group — from 8,1% to 11,4% (p=0,001), in the second — from 5,8% to 8,3% (p=0,0007). In both groups, there was an improvement in microvessel elasticity: a significant decrease in specific peripheral vascular resistance, as well as a significant decrease in total peripheral resistance in the first group (p<0,002) and a tendency to decrease in the second one (p>0,05). There was a significant increase in the stiffness of the aorta and muscular arteries in both groupsю In the first group, a stiffness index decreased from 10,38 m/s to 8,33 m/s (p<0,0001), in the second — from 10,6 m/s to 9,3 m/s (p<0,01). In addition, resistance index in the first group decreased from 71,5% to 60% (p<0,0001), while in the second — from 68% to 60% (p=0,006). Also, both groups showed a significant decrease in the left atrial diastolic dimension and the left atrial volume index. A decrease in the 8-isoprostane plasma levels was noted, which indicates a decrease in oxidative stress. Conclusion. Oxidative stress, which develops due to chronic systemic inflammation, plays a key role in the pathogenesis of HFpEF. The results obtained show an improved endothelial function as a result of decrease in oxidative stress, which is accompanied by an improvement in vessel wall elasticity, thereby slowing down the heart failure progression.