NT-proBNP as a predictor of death and cardiovascular events in patients with type 2 diabetes

Abstract

Existing risk prediction scores based on clinical and laboratory variables have been considered inaccurate in patients with Type 2 Diabetes Mellitus (T2DM). Circulating concentrations of natriuretic peptides have been used to aid in the diagnosis and to predict outcomes in heart failure. However, there is a growing body of evidence for the use of natriuretic peptides measurements, mainly N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a tool in risk stratification for individuals with T2DM. Studies have demonstrated the ability of NT-proBNP to improve outcomes prediction when incorporated into multivariate models. More recently, evidence has emerged of the discriminatory power of NT-proBNP, demonstrating, as a single variable, a similar and even superior ability to multivariate risk models for the prediction of death and cardiovascular events in individuals with T2DM. Natriuretic peptides are synthesized and released from the myocardium as a counter-regulatory response to increased cardiac wall stress, sympathetic tone, and vasoconstriction, acting on various systems and affecting different biological processes. In this article, we present a review of the accumulated knowledge about these biomarkers, underscoring the strength of the evidence of their predictive ability for fatal and non-fatal outcomes. It is likely that, by influencing the functioning of many organs, these biomarkers integrate information from different systems. Although not yet recommended by guidelines, measurement of natriuretic peptides, and particularly NT-proBNP, should be strongly considered in the risk stratification of individuals with T2DM.

Keywords: Biomarkers; Cardiovascular disease; Diabetes, type 2; Morbidity; Natriuretic peptides; Prognosis; Risk assessment.

Fig. 1

NT-proBNP by itself predicted death as well as the 20 clinical and laboratory variables model. Death prediction models by deciles of predicted risk/deciles of NT-proBNP in high-risk patients with Type 2 Diabetes Mellitus. NT-proBNP: N-terminal pro-B-type natriuretic peptide; py = person/years; Base Model: formed by high sensitivity cardiac troponin, age, albumin, history of heart failure, heart rate, history of stroke, HbA1c, smoking, left ventricular hypertrophy on electrocardiogram (ECG), Q wave on ECG, history of atrial fibrillation, any bundle branch block on ECG, urine albumin-to-creatinine ratio, systolic blood pressure, sex, history of coronary heart disease, low-density lipoprotein cholesterol, estimated glomerular filtration rate, insulin use, and diastolic blood pressure, in decreasing order of X²; n = 5509; v = variables. Error bars represent 95% confidence intervals (adapted and reproduced with permission from Malachias et al. [10])

Fig. 2

NT-proBNP by itself predicted cardiovascular composite outcome as well as the 20 variables model. Cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization) prediction models by deciles of predicted risk/deciles of NT-proBNP in high-risk patients with Type 2 Diabetes Mellitus. NT-proBNP: N-terminal pro-B-type natriuretic peptide; py = person/years; Base Model: formed by high sensitivity cardiac troponin, history of heart failure, age, albumin, low-density lipoprotein cholesterol, history of atrial fibrillation, history of stroke, systolic blood pressure, HbA1c, smoking, history of coronary heart disease, sex, urine albumin-to-creatinine ratio, any bundle branch block on electrocardiogram (ECG), diastolic blood pressure, insulin use, Q wave on ECG, heart rate, left ventricular hypertrophy on ECG, and estimated glomerular filtration rate, in decreasing order of X²; n = 5509; v = variables. Error bars represent 95% confidence intervals (adapted and reproduced with permission from Malachias et al. [10])