WNT Signaling Cascade Proteins and LRP6 in the Formation of Various Types of Coronary Lesions in Patients With Coronary Artery Disease.

AIM: Assessment of WNT1, WNT3a, and LRP6 concentrations in patients with ischemic heart disease (IHD) and obstructive and non-obstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 50 IHD patients (verified by coronary angiography, CAG), of which 25 (50%) were men, mean age 64.9±8.1 years; 20 patients had non-obstructive CA disease (stenosis <50%), and 30 patients had hemodynamically significant stenosis. Concentrations of WNT1, WNT3a and LRP6 were measured in all patients. RESULTS: The concentrations of WNT1 and WNT3a proteins were significantly higher in patients with IHD and obstructive CA disease (p < 0.001), while the concentration of LRP6 was higher in the group with non-obstructive CA disease (p = 0.016). Data analysis of the group with obstructive CA disease showed a moderate correlation between WNT1 and LRP6 (ρ=0.374; p=0.042). Correlation analysis of all groups of patients with CA disease revealed a moderate association between the concentrations of WNT1 and uric acid (ρ=0.416; p=0.007). Regression analysis showed that risk factors for the development of IHD, such as increased body mass index, age, smoking, dyslipidemia, and hypertension, did not significantly influence the type of CA disease in IHD patients. According to ROC analysis, the obstructive form of IHD was predicted by a WNT3a concentration higher than 0.155 ng/ml and a LRP6 concentration lower than 12.94 ng/ml. CONCLUSION: IHD patients with non-obstructive CA disease had the greatest increase in LRP6, while patients with obstructive CA disease had significantly higher concentrations of the canonical WNT cascade proteins, WNT1 and WNT3a. According to the ROC analysis, a WNT3a concentration >0.155 ng/ml can serve as a predictor for the presence of hemodynamically significant CA stenosis in IHD patients (sensitivity 96.7%; specificity 70%), whereas a LRP6 concentration >12.94 ng/ml can predict the development of non-obstructive CA disease (sensitivity 76.7%; specificity 65%).

Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

AIM: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. RESULTS: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. CONCLUSION: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

The EXCEL Study: Long-term Observation of the Effectiveness of Drug and Non-drug Rehabilitation in Patients with Ischemic Heart Failure.

AIM: To study the long-term effect of enhanced external counterpulsation (EECP) therapy on exercise tolerance, quality of life (QoL), and indicators of the structural and functional state of the cardiovascular system in patients with stable ischemic heart disease (IHD) complicated by chronic heart failure (CHF). MATERIAL AND METHODS: This open randomized EXCEL study included 120 patients with verified IHD complicated by NYHA II-III functional class CHF with reduced or mid-range left ventricular (LV) ejection fraction. Patients were randomized into group 1 (n=40), optimal drug therapy (ODT) and EECP (35 hours, 2 courses per year); group 2 (n=40), ODT and EECP (35 hours, 1 course per year); and group 3 (control; n=40), ODT and placebo counterpulsation (35 h, 1 course per year). All patients underwent a 6-minute walk test (6MWT), evaluation of clinical status, QoL with the MLHFQ and SF-36 questionnaires, structural and functional state of large blood vessels and microvasculature, measurement of brain natriuretic peptide precursor (NT-proBNP), and echocardiography at baseline and after 12 months. RESULTS: In groups 1 and 2 after 12 months, the 6MWT distance increased statistically significantly (44.5 and 24.9%, respectively) and the following indexes improved: QoL (SF-36, MLHFQ), the condition of large blood vessels (phase shift, radial augmentation index, central aortic systolic pressure (CASP)) and microvasculature (occlusion index, percentage of perfused capillaries, percentage of capillary recovery), and the LV systolic function (from 40.6±7.5 to 47.5±10.2% and from 41.3± 6.8 to 43.9±10.3%, respectively). The proportion of patients with a >20% increase in the 6MWT at 12 months was 97.5, 72.5, and 7.7%, respectively. A statistically significant decrease in NT-proBNP was observed in all groups. In group 3, the incidence of hospitalizations for CHF and the risk of the composite endpoint were significantly higher. CONCLUSION: For the 12-month study period, the effects of EECP in patients with IHD complicated by CHF included improvements in exercise tolerance, QoL, vascular and cardiac functional parameters, and a decrease in the incidence of adverse outcomes.