Features of The Dynamics of Profibrotic Markers and Regression of Left Ventricular Hypertrophy After Renal Denervation in Patients With Resistant Hypertension and Stenosing Atherosclerosis of the Coronary Arteries.

AIM: To compare the changes in serum concentrations of matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMP) to the dynamics of blood pressure (BP) and parameters of left ventricular hypertrophy (LVH) 6 months after renal denervation (RD) in patients with resistant arterial hypertension (RAH) and complicated coronary atherosclerosis. MATERIAL AND METHODS: In 22 RAH patients with complicated coronary atherosclerosis (revascularization and/or history of myocardial infarction (MI)), 24-hour BP monitoring, echocardiography, and measurement of blood MMPs and TIMP were performed at baseline and six months after RD. The comparison group consisted of 48 RAH patients without a history of coronary revascularization or MI. RESULTS: In 6 months after RD, BP was decreased comparably in both groups. In the group of complicated atherosclerosis, there were no significant changes in profibrotic markers or LVH parameters. Thus, at baseline and after 6 months, the values of the studied indicators were the following: left ventricular myocardial mass (LVMM) 233.1±48.1 and 243.0±52.0 g, LVMM index 60.6±14.5 and 62.8±10 .9 g/m2.7, proMMP-1 4.9 [2.1; 7.7] and 3.6 [2.0; 9.4]  ng/ml, MMP-2 290.4 [233.1; 352.5] and 352.2 [277.4; 402.9] ng/ml, MMP-9 220.6 [126.9; 476.7] and 263.5 [82.9; 726.2] ng/ml, TIMP-1 395.7 [124.7; 591.4] and 424.2 [118.2; 572.0] ng/ml, respectively. In the comparison group, on the contrary, there was a significant decrease in LVMM from 273.6±83.3 g to 254.1±70.4 g, LVMM index from 67.1±12.3 to 64.0±14.4 g/m2.7, proMMP-1 from 7.2 [3.6; 11.7] to 5.9 [3.5; 10.9] ng/ml, MMP-2 from 328.9 [257.1; 378.1] to 272.8 [230.2; 343.2] ng/ml, MMP-9 from 277.9 [137.0; 524.0] to 85.5 [34.2; 225.9] ng/ml, and the MMP-9/TIMP-1 ratio from 0.80 [0.31; 1.30] to 0.24 [0.07; 0.76]. The BP dynamics in this group was inversely correlated with MMP-2 at 6 months (r=-0.38), and the MMP-9/TIMP-1 ratio was correlated with LVMM and the LVMM index at baseline (r=0.39 and r=0.39) and at 6 months (r=0.37 and r=0.32). The change in TIMP-1 from 543.9 [277.5; 674.1] to 469.8 [289.7; 643.6] ng/ml was not significant (p=0.060). CONCLUSION: In RAH patients with complicated coronary atherosclerosis, the dynamics of profibrotic biomarkers and LVH parameters after RD was absent despite the pronounced antihypertensive effect, probably due to the low reversibility of cardiovascular remodeling processes or more complex regulatory mechanisms of the MMP system.

Renal hemodynamics in patients with resistant hypertension and type 2 diabetes mellitus.

Aim    To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods    This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results    Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p<0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p<0.001), increases in concentrations of hsCRP (r=0.35, p<0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p<0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p<0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR <60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion    In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).