Resistant arterial hypertension: clinical and pathogenetic peculiarities and predictors of therapy effectiveness

Abstract

The aim – to evaluate the features of the target organs damage, neurohumoral and proinflammatory status and to determine the predictors of the effectiveness of antihypertensive therapy in patients with resistant arterial hypertension (RAH). Materials and methods. The study included 257 patients with apparent RAH. The secondary hypertension was revealed in 8.5 % of patients. After 3 months therapy with triple fixed-dose combination (FDC) of antihypertensive drugs in maximum tolerated doses, patients were distributed into two groups – true RAH (n=103) and patients with pseudo resistant AH (PRAH) (n=132). We performed the comparative analysis of clinical characteristics, target organ damage degree, features of neurohumoral (plasma concentration of aldosterone and active renin, 24 – hour urinary metanephrines) and proinflammatory (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor – α (TNF-α) in plasma) status among groups. The predictors of effectiveness of the 4th antihypertensive drug addition (spironolactone, eplerenone, nebivоlol, moxonidine) to triple FDC in patients with RAH were studied. Results and discussion. Higher levels of office and ambulatory blood pressure (BP), frequent (up to 14 %) disturbance of BP rhythm as night-peaker type, high BP morning surge are typical for RAH patients. 95 % of RAH patients had concentric left ventricular hypertrophy and 80 % – carotid atherosclerosis, a lower glomerular filtration rate and higher level of urinary albumin excretion rate (UAER). RAH patients had higher level of CRP – by 17.3 % (p=0.02), IL-6 – by 21.8 % (p=0.01), TNF-α – by 13 % (p=0.003) in comparison with PRAH patients. The predictors of spironolactone and eplerenone efficacy are plasma aldosterone concentration (β=0.653; p=0.002), aldosterone-renin ratio (β=0.542; p=0.003), UAE (β=–0.362; p=0.01) and the level of CRP (β=–0.315; p=0.03). Conclusions. Higher level of BP, target organ damage, more expressed activation of low – grade inflammation, sympathetic and renin-aldosterone-angiotensin systems activity are typical for RAH patients. The most effective drugs in addition to three – component FDC are MRA – spironolactone and eplerenone, which lead to the achievement of target BP at 48.5 % and 46.9 % (according to office and ambulatory testing) RAH patients. Nebivolol application contributed to BP normalization at 39.7 % and moxonidine – at 41.2 % RAH patients.