Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61

Siddharth M Patel; David A Morrow; Andrea Bellavia; David D Berg; Deepak L Bhatt; Petr Jarolim; Lawrence A Leiter; Darren K McGuire; Itamar Raz; P Gabriel Steg; John P H Wilding; Marc S Sabatine; Stephen D Wiviott; Eugene Braunwald; Benjamin M Scirica; Erin A Bohula

doi:10.1002/ejhf.3118

Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61

Eur J Heart Fail. 2024 Feb;26(2):260-269. doi: 10.1002/ejhf.3118. Epub 2024 Jan 4.

Authors

Siddharth M Patel¹, David A Morrow¹, Andrea Bellavia¹, David D Berg¹, Deepak L Bhatt², Petr Jarolim³, Lawrence A Leiter⁴, Darren K McGuire^{5

6}, Itamar Raz^{7

8}, P Gabriel Steg^{9

10}, John P H Wilding¹¹, Marc S Sabatine¹, Stephen D Wiviott¹, Eugene Braunwald¹, Benjamin M Scirica¹, Erin A Bohula¹

Affiliations

¹ TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA.
³ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁵ Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁶ Parkland Health and Hospital System, Dallas, TX, USA.
⁷ Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
⁹ Université Paris Cité, INSERM U-1148, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹⁰ FACT (French Alliance for Cardiovascular Trials), Paris, France.
¹¹ Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK.

PMID: 38131261
DOI: 10.1002/ejhf.3118

Abstract

Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are lower in patients with obesity. The interaction between body mass index (BMI) and NT-proBNP with respect to heart failure risk remains incompletely defined.

Methods and results: Data were pooled across three randomized clinical trials enrolling predominantly patients who were overweight or obese with established cardiometabolic disease: SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61. Hospitalization for heart failure (HHF) was examined across strata of baseline BMI and NT-proBNP. The effect of dapagliflozin versus placebo was assessed for a treatment interaction across BMI categories in patients with or without an elevated baseline NT-proBNP (≥125 pg/ml). Among 24 455 patients, the median NT-proBNP was 96 (interquartile range [IQR]: 43-225) pg/ml and the median BMI was 33 (IQR 29-37) kg/m², with 68% of patients having a BMI ≥30 kg/m². There was a significant inverse association between NT-proBNP and BMI which persisted after adjustment for all clinical variables (p < 0.001). Within any range of NT-proBNP, those at higher BMI had higher risk of HHF at 2 years (comparing BMI <30 vs. ≥40 kg/m² for NT-proBNP ranges of <125, 125-<450 and ≥450 pg/ml: 0.0% vs. 0.6%, 1.3% vs. 4.0%, and 8.1% vs. 13.8%, respectively), which persisted after multivariable adjustment (adjusted hazard ratio [HR_adj] 7.47, 95% confidence interval [CI] 3.16-17.66, HR_adj 3.22 [95% CI 2.13-4.86], and HR_adj 1.87 [95% CI 1.35-2.60], respectively). In DECLARE-TIMI 58, dapagliflozin versus placebo consistently reduced HHF across BMI categories in those with an elevated NT-proBNP (p-trend for HR across BMI = 0.60), with a pattern of greater absolute risk reduction (ARR) at higher BMI (ARR for BMI <30 to ≥40 kg/m²: 2.2% to 4.7%; p-trend = 0.059).

Conclusions: The risk of HHF varies across BMI categories for any given range of circulating NT-proBNP. These findings showcase the importance of considering BMI when applying NT-proBNP for heart failure risk stratification, particularly for patients with low-level elevations in NT-proBNP (125-<450 pg/ml) where there appears to be a clinically meaningful absolute and relative risk gradient.

Keywords: Biomarkers; Clinical trials; Heart failure; Natriuretic peptides; Obesity; Risk stratification.

MeSH terms

Benzhydryl Compounds / therapeutic use
Biomarkers
Body Mass Index
Glucosides*
Heart Failure* / drug therapy
Heart Failure* / epidemiology
Humans
Natriuretic Peptide, Brain / therapeutic use
Obesity / complications
Obesity / epidemiology
Peptide Fragments / therapeutic use
Prognosis

Substances

dapagliflozin
Biomarkers
Natriuretic Peptide, Brain
Benzhydryl Compounds
Peptide Fragments
Glucosides

Abstract

MeSH terms

Substances

Grants and funding