The dissertation is devoted to solvе the urgent problem of cardiology to increase the effectiveness of treatment while studying the characteristics of ABPM data, metabolic, proinflammatory and humoral status in patients with RAH and kidney damage and determine the previous dynamics of their functional status.
The study included patients aged 18 to 79 years, with uncontrolled hypertension according to office blood pressure measurement (≥ 140/90mm Hg) on the background of taking at least 3 antihypertensive drugs in the maximum tolerated doses one of which is a diuretic.
At the stage of diagnosis, all patients were prescribed a triple fixed-dose combination (FD) RAAS blocker / thiazide (thiazide-like) diuretic / calcium antagonist in the maximum tolerated doses for 3 months in order to standardize therapy. According to the results of this therapy, patients were divided into 2 groups: the group with controlled hypertension (CAH) (114 patients), in which after 3 months of treatment with triple FD combination managed to achieve the target BP, office and outpatient BP and the group with resistant hypertension (RAH) (117 patients) - blood pressure remained above the target level.
Patients with RAH continued treatment with the addition of the 4th component of therapy, which were alternately antagonists of mineralocorticoid receptors spironolactone or eplerenone, beta-blocker nebivolol, imidazoline receptor agonist moxonidine and diuretic torasemide for 3 months. At the end of each stage, after 3 months of therapy, patients were examined: measurment office blood pressure, ABPM, determination of blood levels of potassium, sodium and creatinine.
To study the characteristics of patient’s clinical profile with RAG, a comparative analysis of data of 117 patients with RAH and 114 patients with CAG was performed. At the stage of primary screening, 54 patients with RAH had CKD, and in the group of CAH were 16 patients with CKD, that was 46,2% and 14%, respectively (χ2 = 29,00; р < 0,001). In addition, patients with RAH had type 2 diabetes – in 4,9 times more common than in the group of CAH: 38,5 % vs. 7,9 % (χ2 = 31.21; p <0.001).
A comparative analysis of ABPM in groups without and with CKD revealed that patients with reduced renal function had significantly higher pulse arterial pressure (PAP) rates: daily average by 8,2 % (p = 0,03) and the average nightly rate of 9,8 % (p = 0,02). Compared with patients without diabetes, patients with diabetes have level of both - office (by 18,7 %; p = 0,005), average daily (by 20,4 %; p <0,001) and the average nightly (by 15,8%; p <0.004) was higher.
Analysis of the structural and functional state of the kidneys showed that in the absence of CKD at the initial examination, GFR was slightly but significantly lower in patients with CAH - by 8,7 % (p = 0,008). However, patients with RAH had significantly higher rates of albuminuria – 21,7 % (p = 0,03) and plasma cystatin C - by 54,5 % (p <0,001) and, accordingly, lower GFR estimated by cystatin C - by 19,7% (p = 0,006). No difference in the structural parameters of the kidneys was found in patients with RAH and CAH and concomitant CKD.
The higher level of pro-inflammatory parameters in patients with RAH, compared with patients with CAH, due to the activation of low-grade inflammation in patients with CKD. Thus, in the presence of CKD, the content of CRP in blood by 15,0%, TNF-α by 37,9%, IL-6 by 66,7% (p <0,001 for all indicators) were higher compared with the group without CKD. Increasing of CRP and proinflammatory cytokines corresponds to the increase in the stage of CKD. In addition, level of active plasma renin was 23,3 % (p = 0.01) higher in patients with RAH and CKD in comparison with patients without CKD.
In patients with RAH without concomitant diabetes, level of GFR was achieved against the background of effective antihypertensive therapy. In contrast, in patients with RAH and concomitant diabetes without CKD, despite a significant improvement in blood pressure control, renal function deteriorated - during GFR observation decreased by 8,4 ml / min / 1.73m2, accompanied by an increase in albuminuria by 2,2 times against the background of an increase in glycemia during observation.
At the end of the study, the target level of office blood pressure was reached by 66,7 % of patients with RAH without CKD (42 patients), while in patients with renal damage, this figure was significantly lower and amounted to 44,4 % (24 patients) (χ2 = 12,3 ; p = 0,001). Outpatient blood pressure targets were achieved by only 55,5% of patients with preserved renal function (35 patients) and only 35,2 % of patients with CKD (19) (χ2 = 10,8; p = 0,02). Thus, the frequency of masked uncontrolled hypertension was comparable in patients of the comparison groups – 11,2 versus 9,2% in the group without and with CKD, respectively.
