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

J Am Heart Assoc. 2020 Oct 20;9(19):e017462. doi: 10.1161/JAHA.120.017462. Epub 2020 Sep 23.


Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. Methods and Results Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT-proBNP alone and with NT-proBNP added, using C-statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6-year follow-up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT-proBNP alone was as discriminatory as the base model for predicting death (C-statistic, 0.745 versus 0.744, P=0.95) and the cardiovascular composite outcome (C-statistic, 0.723 versus 0.731, P=0.37). When NT-proBNP was added, it increased the predictive ability of the base model for death (C-statistic, 0.779 versus 0.744, P<0.001) and for cardiovascular composite outcome (C-statistic, 0.763 versus 0.731, P<0.001). Conclusions In high-risk patients with T2DM, NT-proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00549757.

Keywords: cardiovascular diseases; diabetes complications; diabetes mellitus; proportional hazards models; pro‐B-type natriuretic peptide; type 2.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides / administration & dosage*
  • Antihypertensive Agents / administration & dosage
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Complications / blood
  • Diabetes Complications / mortality
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / mortality
  • Double-Blind Method
  • Female
  • Fumarates / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models*
  • Risk Assessment / methods*


  • Amides
  • Antihypertensive Agents
  • Fumarates
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • aliskiren

Associated data

  • ClinicalTrials.gov/NCT00549757