CARDIOMETABOLIC DETERMINANTS OF ELEVATED NT-proBNP CONCENTRATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ARTERIAL HYPERTENSION (LITERATURE REVIEW AND ORIGINAL DATA)

Abstract

The combination of arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) is associated with a high risk of cardiac remodeling, left ventricular diastolic dysfunction, and the development of heart failure. The N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) is considered a sensitive biomarker of myocardial stress, increased left ventricular filling pressure, and early structural and functional cardiac changes. However, the cardiometabolic factors determining elevated NT-proBNP concentrations in patients with combined AH and T2DM remain insufficiently studied.

Aim To determine the cardiometabolic determinants of elevated NT-proBNP concentrations in patients with type 2 diabetes mellitus and arterial hypertension.

Materials and Methods The study included 136 patients with AH, divided into two groups: the first group comprised patients with isolated AH (n = 64), and the second group comprised patients with AH combined with T2DM (n = 72). The control group consisted of 20 apparently healthy individuals. All participants underwent a comprehensive clinical, laboratory, and instrumental examination, including assessment of lipid profile parameters, HbA1c, insulin, leptin, cystatin C (Cys C), NGAL, and NT-proBNP by enzyme-linked immunosorbent assay; evaluation of lymphocyte subpopulations; assessment of renal function parameters; and echocardiographic evaluation. To determine the factors associated with elevated NT-proBNP concentrations, univariate and multivariate logistic regression analyses were performed, with odds ratios and 95% confidence intervals calculated, and the prognostic performance of the models assessed using ROC analysis.

Results Patients with combined AH and T2DM had a more unfavourable cardiometabolic profile than patients with isolated AH. This was manifested by higher body mass index, total cholesterol, triglycerides, and atherogenic coefficient, increased leptin levels, activation of the cellular immune system, and more pronounced structural and functional cardiac remodelling. In the AH + T2DM group, increased left ventricular myocardial mass, left ventricular mass index, cardiac chamber dimensions, reduced left ventricular ejection fraction, and impaired diastolic function parameters were observed. NT-proBNP concentrations in patients with AH + T2DM tended to be higher than in the isolated AH group; however, the between-group difference did not reach statistical significance (p = 0.0791).

According to multivariate logistic regression analysis, in patients with isolated AH, independent predictors of elevated NT-proBNP concentrations were aortic size and left ventricular myocardial mass; the model’s prognostic performance was good (AUC = 0.868). In patients with combined AH and T2DM, the independent cardiometabolic determinants of elevated NT-proBNP concentrations were isovolumic relaxation time (IVRT), early diastolic filling velocity (VE), left ventricular mass index indexed to height, insulin concentration, and systolic blood pressure. The multivariate model in the AH + T2DM group also demonstrated good prognostic performance (AUC=0.803). Conclusion Elevated NT-proBNP concentrations in patients with AH and T2DM are formed under the influence of a complex of hemodynamic, metabolic, and structural-functional factors. In isolated AH, cardiac remodelling parameters are of primary importance, whereas in combined AH and T2DM, the spectrum of determinants expands to include indicators of diastolic dysfunction, left ventricular hypertrophy, insulin homeostasis, and systolic blood pressure. NT-proBNP may be considered an integral biomarker of early cardiac remodelling, subclinical diastolic dysfunction, and cardiometabolic risk stratification in patients with comorbid AH and T2DM.