Physicians' Academy for Cardiovascular Education

NT-proBNP by itself predicts mortality and CV outcomes in T2DM

NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus

Literature - Malachias MVB, Jhund PS, Claggett BL, et al. - J Am Heart Assoc. 2020;9:e017462. DOI: 10.1161/JAHA.120.017462

Introduction and methods

B-type natriuretic peptides (BNP) are biomarkers for myocardial stress and well established predictors of heart failure (HF) outcomes [1,2]. BNPs are also, when incorporated in multivariable hazard models, a predictor of death and CV events in individuals with type 2 diabetes [3-6], especially in those who have a comorbidity of HF [7,8], chronic kidney disease (CKD) [9-11] or recent acute coronary syndrome [12,13]. But despite the improved discriminatory strength of this marker in risk models for T2DM, NT-proBNP has not been used for risk assessment in clinical practice.

The current study assessed the discriminatory ability of NT-proBNP alone in predicting the risk of death and CV outcomes in 5509 patients with T2DM and CVD and/or CKD using data from the Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) trial.

The ALTITUDE trial was a randomized, double-blind, placebo-controlled, parallel group study in patients with type 2 diabetes. Individuals (≥35 years) received antidiabetic drugs or had a documented fasting plasma glucose of ≥126 mg/dL or 2-hour plasma glucose ≥200 mg/dL and were either on ACE-inhibitors or ARBs without any change in antihypertensive therapy for at least 4 weeks before randomization. Participants were also diagnosed with persistent macroalbuminuria (albumin-to-creatinine ratio ≥200 mg/g) and an eGFR ≥30 mL/min/1.73m², or microalbuminuria (albumin-to-creatinine ratio ≥20 mg/g) and/or a history of CV disease (MI, stroke, HF, or coronary artery disease) and a reduced kidney function (eGFR ≥30 mL/min/1.73 m²). Patients were subdivided into 10 deciles based upon risk prediction or NT-proBNP concentration levels (<36, 37-62, 63-92, 93-128, 129-176, 177-244, 245-348, 349-544, 545-1002, and >1003 pg/mL). The endpoints were all cause death and CV events defined as CV death, resuscitated cardiac arrest, nonfatal MI, nonfatal stroke, or unplanned HF hospitalization. Median follow-up was 2.6 years.

Three risk models were generated: 1) a multivariable base model with 20 important clinical variables, 2) an univariable NT-proBNP model, and 3) the multivariable base model combined with the NT proBNP model. The risk prediction performance of the NT-proBNP only model was compared to that of the base risk model and the base model plus NT-proBNP, using C-statistics.

Main results


NT-proBNP was a biomarker with a discriminatory ability to predict both death and CV events as accurately as the multivariable risk model in T2DM patients with CVD and/or CKD comorbidity. NT-proBNP significantly improved the risk stratification of high-risk T2DM patients when added to the multivariable risk prediction model.


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Find this article online at J Am Heart Assoc.

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