Dynamics of Vascular Stiffness and Endothelial Function in Combination Therapy of Heart Failure with Preserved Ejection Fraction

Aim. To assess the effect of combination therapy (perindopril, indapamide, amlodipine) on vascular stiffness and endothelial function in patients with heart failure with preserved ejection fraction (HFpEF).Material and methods. Patients with HFpEF (n=30) were included in a nonrandomized, uncontrolled trial. All patients had a comprehensive examination: a six-minute walk test to determine exercise tolerance, echocardiography, determination of the diameter of the brachial artery with an assessment of its endothelium-dependent vasodilation (EDVD). Photoplethysmography and compression oscillometry were also carried out to assess the stiffness characteristics of vessels of various calibers and the determination of the cardio-ankle vascular index. Patients were examined initially and 16 weeks after the combination therapy order (perindopril 10 mg/day, indapamide 2.5 mg/day, amlodipine 5 mg/day).Results. The data obtained during therapy shows improvement of the endothelial function for all patients: the initial EDVD was 8.5%, by the end of the observation period it increased to 11.4% (p=0.007). A significant decrease in the systemic vascular resistance from 2591 dyn*cm-5 to 2380 dyn*cm-5 (p=0.03) and in the level of specific peripheral resistance from 32.9 dyn/sec/cm-5 to 28.5 dyn/sec/cm-5 (p=0.0051). The stiffness indices of small resistive vessels also decreased: vascular stiffness index from 10.2±2.2 m/sec to 8.4±2.5 m/sec (p<0.0001) and pulse wave reflection index from 70.2±13.5% to 61.9±14.7% (p=0.0011). Cardio-ankle vascular index (CAVI) initially amounted to 9.2±1.3 and decreased by the end of the observation period during treatment to 8.3±1.1 (p=0.0003). The pulse blood pressure was significantly decrease from 71.31±15.5 mm Hg to 64.5±12.9 mm Hg (p=0.0048) and there was a tendency to decrease in pulse wave velocity from 808 cm/sec to 730 cm/sec.Conclusion. The results of the study showed a statistically significant improvement in the elastic component of small resistive and major vessels, the endothelial function. The obtained results prove a decrease in the stiffness characteristics of blood vessels during the combination therapy.This suggests that the combination of drugs with a different mechanism of action improves not only the state of the endothelium and its function, but also significantly reduces the stiffness of the great vessels, restores the microcirculatory support of the interstitium of the myocardium and vascular wall in patients with HFpEF and leads to an improvement in the clinical status of patients with this syndrome

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

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 2,5mg 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