Background: N-terminal pro–B-type natriuretic peptide (NT-proBNP) identifies elevated risk for developing heart failure (HF) in type 2 diabetes (T2D). Whether risk of HF subtypes associated with NT-proBNP is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown.
Objectives: This study aims to evaluate the association of baseline and longitudinal changes in NT-proBNP with risk of HF subtypes in T2D. In addition, we assessed whether NT-proBNP modified the association of an ILI with risk of HF subtypes.
Methods: Adults with T2D and overweight or obesity in the Look AHEAD trial were included (n = 3,959). Associations of baseline and 1-year changes in NT-proBNP with risk of HF subtypes (left ventricular ejection fraction ≥50% [heart failure with preserved ejection fraction (HFpEF)] and <50% (heart failure with reduced ejection fraction (HFrEF)] were evaluated in adjusted Cox models. Multiplicative interaction testing was performed to evaluate heterogeneous treatment effects of the ILI on HF subtypes across NT-proBNP concentrations.
Results: Elevated NT-proBNP (≥125 pg/mL) at baseline and increasing NT-proBNP over 1-year follow-up (vs stable or decreasing) were each significantly associated with higher risk of both HF subtypes. The ILI was associated with lower HFpEF risk among participants with elevated but not nonelevated baseline NT-proBNP (HRs for ILI vs diabetes support and education (DSE): HR: 0.47 (95% CI: 0.24-0.90) and HR: 1.65 (95% CI: 0.93-2.91), respectively; P for interaction = 0.003). Participants with stable or decreasing, but not increasing, NT-proBNP at 1-year follow-up had lower HFpEF risk with the ILI (HRs for ILI vs DSE: HR: 0.58 (95% CI: 0.34-0.99) and HR: 1.48 (95% CI: 0.61-3.56), respectively; P for interaction = 0.01). The ILI was not significantly associated with HFrEF risk across baseline or 1-year change in NT-proBNP categories.
Conclusions: In T2D, NT-proBNP can inform HF risk assessment and identify individuals who are more likely to benefit from an ILI. (Look AHEAD: Action for Health in Diabetes [Look AHEAD]; NCT00017953.
Editors
JACC Heart Failure Editor-in-Chief
Biykem Bozkurt, MD, PhD, FACC
Deputy Editor
Akshay S. Desai, MD, MPH
JACC Heart Failure CME/MOC Editor
Kenneth A. Ellenbogen, MD
Author
Bhaskar Arora, MD, FACC
Important Dates
Date of Release: March 2, 2026
Term of Approval/Date of CME/MOC Expiration: March 1, 2027