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).

[Systemic inflammatory response in cardiac surgery: possibilities of using colchicine].

AIM: To evaluate manifestations of systemic inflammatory response (SIR) and the effect of the colchicine therapy on SIR severity in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) with extracorporeal circulation (EC). MATERIAL AND METHODS: This study included 100 patients aged 62+6.3 years with stable IHD and multivessel coronary atherosclerosis scheduled for CABG with EC. Patients of group 1 (n=50) were administered with a single dose of colchicine (Colchicum-Dispert) 500 µg 4 hours before surgery followed by 500 µg twice a day for 10 days after surgery. Patients of group 2 (n=50) received a standard treatment, including nonsteroid anti-inflammatory drugs after surgery. Severity of the inflammatory response was evaluated by measuring blood cytokines. RESULTS: In the postoperative period, patient of group 1 showed a tendency toward a lower incidence of pleurisy and heart rhythm disorders in the form of paroxysmal atrial fibrillation (AF) (p=0.18). Levels of the anti-inflammatory cytokines, interleukin-10 (IL-10) and interleukin-6 (IL-6), were significantly increased in both groups at 6 hours after surgery (p<0.05); at the same time, in group 1, IL-10 remained increased also at 10 days after surgery (р=0.0002). No significant time-related changes in the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß), were observed. At 3 days post-CABG, there were significant increases in tissue inhibitors of matrix metalloprotease 1 (TIMP-1) (р<0.0001) and matrix metalloproteinase 9 (MMP-9) (р<0.001); at the same time, patients of group 1 had lower MMP-9 concentrations than patients of group 2 (p<0.05). At 10 days of postoperative period, these values were comparable with the background values. Increases in neopterin compared to preoperative values were found in both groups on days 3 and 10 after surgery (р <0.0001). CONCLUSION: CABG with EC is associated with the activation of SIR. The colchicine therapy at a dose of 500 µg 4 hours prior to surgery and 500 µg twice a day for 10 days after surgery reduces manifestations of SIR, which is clinically evident as a tendency to reduced incidence of pleurisy and arrhythmias, and does not result in the development of serious complications. The dynamics of matrix metalloproteinases indicates that the colchicine treatment is promising for decreasing the risk of CHF progression and myocardial remodeling in patients with IHD.

Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction In Patients With Resistant Hypertension and Type 2 Diabetes Mellitus.

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabolic, proinflammatory and profibrotic biomarkers, increased vascular wall stiffness, pronounced left ventricular hypertrophy, and with structural and functional alterations in kidneys.

Bone Remodeling Markers in Assessing of Sternal Reparative Regeneration in Patients With Carbohydrate Metabolism Disorders After Coronary Bypass Surgery.

Aim      To study time-related changes in bone remodeling markers in patients with ischemic heart disease (IHD) associated with type 2 diabetes mellitus (DM) and disorders of carbohydrate metabolism (CM). Also, a possibility was studied of using these markers for evaluation of breast bone reparative regeneration in early and late postoperative periods following coronary bypass (CB).Materials and methods           This study included 28 patients with IHD and functional class II-III exertional angina after CB. Patients were divided into 2 groups based on the presence (group 1) and absence (group 2) of CM disorders. Contents of osteocalcin (OC), C-terminal telopeptide (CTTP) of type 1 collagen, deoxypyridinoline (DPD), and alkaline phosphatase bone isoenzyme (ALPBI) were measured by enzyme immunoassay on admission (Т1) and at early (Т2) and late (Т3) postoperative stages. Sternal scintigraphy with a radiopharmaceutical (RP) was performed at stage 3 following sternotomy.Results The content of OC and CTTP was reduced in group 1 compared to the values in the group without CM disorders (р<0.005) at stages Т1 and Т2. There were no significant intergroup differences in concentrations of ALPBI and DPD throughout the study. Time-related changes in OC, CTTP, and DPD had some intergroup differences: the increase in biomarkers was observed in group 1 considerably later, at stage Т3 (р<0.005), while in group 2, it was observed at stage T2 after sternotomy. Scintigraphy revealed significant intergroup differences in the intensity of RP accumulation in sternal tissue.Conclusion      The intergroup differences in the content of biomarkers evidenced a disbalance among processes of formation and resorption of bone tissue and delayed remodeling processes in patients with IHD associated with type 2 DM and CM disorders. The study confirmed significance of comprehensive evaluation of time-related changes in markers for bone tissue metabolism and sternal scintigraphy for diagnosis and evaluation of sternal reparative regeneration following sternotomy in patients with IHD associated with type 2 DM and disorders of CM metabolism.

[Role of markers of inflammation and endothelial dysfunction in the prognosis of the development of cardiovascular complications in patients with coronary artery disease and metabolic syndrome after coronary stenting].

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 (р<0.001). Concentrations of endothelin 1 were 1.9 times higher in group 1 and 3.7 times higher in the MS group compared to the control. At one year after PCI, the incidence of adverse outcomes in the form of cardiovascular events was higher for patients with MS: 10 (20.8 %) cases of stent restenosis and 13 (27.1 %) episodes of coronary atherosclerosis progression according to results of repeated coronarography vs. 2 (6.3%) restenosis cases (χ2-10.853; р=0.002) and 2 (6.3%) episodes of atherosclerosis progression (χ2-23.651; р=0.001) for patients without MS. The groups did not differ in rates of myocardial infarction and cardiac death. The most significant predictors of unfavorable prognosis were LP-PLA2 concentration >983.83 ng/ml (area under the ROC curve, 0.867; sensitivity, 80 %; specificity, 100%; р<0.001) and endothelin 1 overexpression >0.852 fmol/ml (area under the ROC curve, 0.885; sensitivity, 85.5 %; specificity, 83.6 %; р<0.001).Conclusion Patients with MS were characterized by more pronounced imbalance of pro- and anti-inflammatory factors. Concentrations of LP-PLA2 >983.83 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.