Differences in the effects of various classes of antihypertensive drugs in combination therapy on indicators of arterial hemodynamics, vascular wall stiffness and structural-functional state of heart in patients with arterial hypertension of 1 — 2 degrees
Authors: K. M. Amosova  , K. P. Lazareva  , Yu. V. Rudenko  , G. V. Mostbauer  , P. O. Lazariev  , N. V. Shyshkina  , O. V. Vasylenko  
Published: January 2019

The aim —  to compare the effect of 6‑month treatment of patients with arterial hypertension (AH) of 1 — 2 degrees with angiotensin converting enzyme (ACE) or angiotensin II receptor blockers (ARB) in combination with a thiazide diuretic (indapamide) and dihydropyridine calcium channel blockers (CCB) in combination with a diuretic on indicators of brachial and central arterial pressure (AP), elastic properties of the arteries and the structural and functional state of the heart, depending on age.Materials and methods. The study included 320 patients (156 men and 164 women) aged from 35 to 80 years (mean age 62.8 ± 0.61 years) with uncomplicated AH of stage I — II, degree 1 — 2 (62.0 % and 38, 1 %, correspondingly). Depending on age, the patients were divided into two groups: < 65 years old (n = 157) and ≥ 65 years old (n = 163), the ratio of men and women was approximately 1 : 1. Using the method of blind envelopes patients of each group were randomized into 2 subgroups: subgroup «A» — that received therapy based on an ACE inhibitor (perindopril 5 — 10 mg) or ARB (olmesartan 20 — 40 mg), and subgroup «B» who received therapy based on CCB (lercanidipine 5 — 10 mg). Patients ≥ 65 years old, randomized to subgroup «B», began treatment with a fixed combination of indamapid 1.5 mg +amlodipine 5 mg (Arifam, Servier, France). If the target office brachial AP was not achieved (< 140/90 mm Hg), the dose of each of the studied antihypertensive drugs was increased to full therapeutic. If necessary, patients of subgroup «A» and patients aged < 65 years old of subgroups «B» were additionally given indapamide at a dose of 2.5 mg 1 time per day. Patients who were prescribed Arifam, if necessary, increased the dose to 1.5/10 mg. The patients underwent general clinical examination, measurement of brachial arterial pressure, pulse wave analysis and measurement of carotid‑femoral and carotid‑radial pulse wave velocity using applanation tonometry, Doppler echocardiography. The parameters of arterial wall stiffness (Ea), myocardial wall stiffness (Ees) of the left ventricle (LV), coefficient of ventricular‑arterial interaction (Еа/Еes) were calculated.Results and discussion. The study involved a total of 284 patients (145 men and 139 women), including those aged < 65 years in group «A» (41 men and 30 women), group «B» (37 men and 29 women), aged ≥ 65 years in group «A» (30 men and 30 women), and group «B» (37 men and 50 women). After 6 months of treatment, patients aged < 65 years in both subgroups reliably decreased brachial systolic, brachial diastolic, mean brachial AP, which was accompanied by a decrease in central systolic, central diastolic, central pulse, mean central AP, total peripheral vascular resistance (р < 0.01, р < 0.001). As a result of treatment, office brachial AP of 140/90 mm Hg was achieved in 69.0 % patients aged < 65 years in subgroup «A» and in 67.0 % patients of subgroup «B» (р > 0.05). In both subgroups of patients aged < 65 years, a decrease in pressure and augmentation index was observed, including that normalized by heart rate (HR) of 75 per 1 min (AP, АІх, АІх75), carotid‑femoral and carotid‑radial pulse wave velocity (all p < 0.01 and p < 0.001). There were no significant changes in the systolic and diastolic functions of the left ventricle, except for a decrease in the myocardial mass index (MMI) of the left ventricle in the group treated with a combination of CCB with indapamide by 7.1 % (p < 0.05) and e’ of the septum by 7.6 % (p < 0.05). In patients aged ≥ 65 years, the absolute decrease in central systolic AP in two subgroups was 23.20 ± 1.34 and 16.30 ± 1.94 mm Hg, respectively, (p < 0.01). The groups did not differ significantly in brachial pulse and central pulse BP (p > 0.05). In the group treated with Arifam, the baseline HR values correlated with AP (r = –0.357, p < 0.01), AІx (r = –0.274, p < 0.05), but not with AIx75, central systolic AP and mean central AP (p > 0.05). In patients aged ≥ 65 years, the antihypertensive effect of therapy with the combination of ACE inhibitor/ARB and indapamide was not accompanied by changes in MMI LV and indicators of LV systolic and diastolic function (all p > 0.05). In the group treated with Arifam there was a decrease in end‑diastolic and end‑systolic volumes (by 9.7 % (p < 0.05) and 10.8 % (p < 0.01)), an increase in LV ejection fraction by 3.6 % (p < 0.05), a decrease in MMI of LV by 12.5 % (p < 0.001), an increase in volume index of the left atrium by 11.0 % and E/E’ by 8.83 % (p < 0.05). In both subgroups of patients aged < 65 years, Ea and Еes decreased equally (p < 0.001). Against the background of antihypertensive therapy, the patients aged ≥ 65 years had a decrease in Ea, which was accompanied by a decrease in Ees in the group treated with ACE inhibitor/ARB and indapamide (p < 0.05), but Ea/Ees ratio did not change significantly in two age groups (p > 0.05).Conclusions. In spite of the same positive effect of 6‑month therapy with combinations of ACE inhibitors/ARB with indapamide and BPC with indapamide on brachial and central AP in older patients with hypertension of 1 — 2 degrees, the fixed combination of BPC amlodipine with indapamide (Arifam) had an advantage over the combination based on an ACE inhibitor (ARB) regarding the reduction of brachial, central, mean brachial and mean central AP, augmentation, pulse wave velocity, MMI of LV, left atrium volume index, E/e’ of LV, which was associated with an increase in heart rate (an average of 4.6 per 1 min).