Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

(1) Background: The results of the international studies support the assumption that coronary microvascular dysfunction (CMD) occurs significantly more often than previously identified and is associated with adverse outcomes. However, there is a lack of the accurate comprehension of its pathophysiology. The objectives of this study were to evaluate the clinical and instrumental features of CMD and to assess its prognostic value during 12 months of follow-up period. (2) Methods: A total of 118 patients with non-obstructive coronary artery disease (CAD) and preserved LV ejection fraction (62 [59; 64]%) were enrolled in the study. Serum levels of biomarkers were analyzed by enzyme-linked immunoassay. CMD was defined as the reduced myocardial flow reserve (MFR) ≤ 2 obtained by dynamic CZT-SPECT. Two-dimensional transthoracic echocardiography with evaluation of LV diastolic dysfunction was performed baseline. (3) Results: Patients were divided into groups depending on the presence of CMD: CMD+ group (MFR ≤ 2; n = 45), and CMD− group (MFR > 2; n = 73). In CMD+ group, the severity of diastolic dysfunction, the levels of biomarkers of fibrosis and inflammation were higher than in CMD− group. Multivariate regression analysis showed that the presence of diastolic dysfunction (OR 3.27; 95% CI 2.26–5.64; p < 0.001), the hyperexpression of NT-proBNP ≥ 760.5 pg/mL (OR 1.67; 95% CI 1.12–4.15; p = 0.021) and soluble ST2 ≥ 31.4 ng/mL (OR 1.37; 95% 1.08–2.98; p = 0.015) were independent factors associated with CMD. Kaplan–Meier analysis showed that a rate of the adverse outcomes was significantly (p < 0.001) higher in patients with CMD (45.2%, n = 19) than in patients without it (8.6%, n = 6). (4) Conclusions: Our data suggest that the presence of CMD was associated with the severe diastolic dysfunction and hyperexpression of the biomarkers of fibrosis and inflammation. Patients with CMD had higher rate of the adverse outcomes than those without it.

Aim      To compare the antihypertensive effectivity of renal denervation in patients with diabetes mellitus (DM) and associated refractory arterial hypertension (rfAH) (treated with 5 or more classes of antihypertensive drugs, including a thiazide diuretic and a mineralocorticoid receptor antagonist) and uncontrolled resistant AH (ucAH) (treated with 3-4 drugs). Material and methods  This interventional study with renal denervation included 18 DM patients with rfAH and 40 DM patients with ucAH; 16 and 36 of them, respectively, completed the study in 6 months. At baseline, patients were sex- and age-matched. Study methods included measurement of office blood pressure (BP; systolic/diastolic BP, SBP/DBP); outpatient BP monitoring; evaluation of kidney function (estimated glomerular filtration rate by the CKD-EPI formula); diurnal diuresis volume; diurnal urinary excretion of albumin, potassium and sodium; diurnal excretion of metanephrines and normetanephrines; and plasma levels of glucose and glycated hemoglobin, aldosterone, and active renin. Patients were instructed about maintaining compliance with their antihypertensive and hypoglycemic therapy throughout the study. Results At baseline, patients of both groups were comparable by BP and major clinical indexes, except for higher values of nocturnal SBP variability (p<0.05) in patients with rfAH. At 6 months following renal denervation, both groups displayed significant decreases in office and average daily SBP and also in the “load” with increased mean diurnal SBP. However, the decrease in average daily SBP was almost 4 times greater in the rfAH group than in the ucAH group ( –19.9 and –5.1 mm Hg, respectively, р=0.02). Moreover, 81 % of patients in the rfAH group responded to the intervention (average daily SBP decrease ≥10 mm Hg) while the number of responders in the ucAH group was considerably smaller (42 %; p=0.02). In patients with rfAH, renal denervation was associated with a significant decrease in pulse BP and nocturnal SBP variability and with the increase in diurnal diuresis. No other alterations were noted in laboratory test results in either group. Conclusion      DM patients with rfAH may be the best candidates for the procedure of renal denervation.

Aim To study the role of inflammation markers and endothelial dysfunction in predicting the risk of cardiovascular event following a percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD) and metabolic syndrome (MS). Materials and methods 80 patients (72 men; median age, 56 (50;63) years) with IHD and PCI were evaluated. Based on the presence of MS according to NCEP-ATP III criteria, patients were divided into two groups, group 1 without MS (n=32) and group 2 with MS (n=48). The control age- and sex-matched group included 15 people without cardiovascular diseases. Serum concentrations of tumor necrosis factor α (TNFα), interleukin 6 (IL-6), IL-10, lipoprotein-associated phospholipase A2 (LP-PLA2), and endothelin 1 were measured by enzyme-linked immunosorbent assay (ELISA). Patients were followed up for 12 months after PCI with evaluation of the incidence of adverse cardiovascular events. Statistical analysis was performed with Statistica 10.0 and Medcalc 19.2.6 software. Differences between variables were considered statistically significant at р<0.05. Potential predictors were determined by the ROC analysis with construction of ROC curves, calculation of AUC (area under the curve), identification of COP (cut-off point by the Youden’s index), and sensitivity (Se) and specificity corresponding to the COP. Results Patients with MS had statistically significantly higher serum levels of inflammatory markers than patients of the control group. Concentration of the intravascular inflammation marker, PL-PLA2, was 2.7 times higher in group 1 and 5.1 times higher in group 2 than in the control group (р983.83 ng/ml (area under the ROC curve, 0.867; sensitivity, 80 %; specificity, 100%; р0.852 fmol/ml (area under the ROC curve, 0.885; sensitivity, 85.5 %; specificity, 83.6 %; р983.83 ng/ml and endothelin 1 >0.852 fmol/ml were shown to be predictors of unfavorable prognosis for patients with IHD and MS after PCI with coronary stenting.

Ренальная денервация как новая стратегия нефропротекции у больных резистентной артериальной гипертонией, ассоциированной с сахарным диабетом 2-го типа