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

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

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	260-269
Number of pages	10
Journal	European Journal of Heart Failure
Volume	26
Issue number	2
DOIs	https://doi.org/10.1002/ejhf.3118
State	Published - Feb 2024
Externally published	Yes

Keywords

Biomarkers
Clinical trials
Heart failure
Natriuretic peptides
Obesity
Risk stratification

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1002/ejhf.3118

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Patel, S. M., Morrow, D. A., Bellavia, A., Berg, D. D., Bhatt, D. L., Jarolim, P., Leiter, L. A., McGuire, D. K., Raz, I., Steg, P. G., Wilding, J. P. H., Sabatine, M. S., Wiviott, S. D., Braunwald, E., Scirica, B. M., & Bohula, E. A. (2024). Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61. European Journal of Heart Failure, 26(2), 260-269. https://doi.org/10.1002/ejhf.3118

Patel, SM, Morrow, DA, Bellavia, A, Berg, DD, Bhatt, DL, Jarolim, P, Leiter, LA, McGuire, DK, Raz, I, Steg, PG, Wilding, JPH, Sabatine, MS, Wiviott, SD, Braunwald, E, Scirica, BM & Bohula, EA 2024, 'Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61', European Journal of Heart Failure, vol. 26, no. 2, pp. 260-269. https://doi.org/10.1002/ejhf.3118

@article{5706925db3cd4387b6e60958c72b341e,

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

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 [HRadj] 7.47, 95% confidence interval [CI] 3.16–17.66, HRadj 3.22 [95% CI 2.13–4.86], and HRadj 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",

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

note = "Publisher Copyright: {\textcopyright} 2023 European Society of Cardiology.",

year = "2024",

month = feb,

doi = "10.1002/ejhf.3118",

language = "English (US)",

volume = "26",

pages = "260--269",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Natriuretic peptides, body mass index and heart failure risk

T2 - Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61

AU - Patel, Siddharth M.

AU - Morrow, David A.

AU - Bellavia, Andrea

AU - Berg, David D.

AU - Bhatt, Deepak L.

AU - Jarolim, Petr

AU - Leiter, Lawrence A.

AU - McGuire, Darren K.

AU - Raz, Itamar

AU - Steg, P. Gabriel

AU - Wilding, John P.H.

AU - Sabatine, Marc S.

AU - Wiviott, Stephen D.

AU - Braunwald, Eugene

AU - Scirica, Benjamin M.

AU - Bohula, Erin A.

PY - 2024/2

Y1 - 2024/2

N2 - 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 [HRadj] 7.47, 95% confidence interval [CI] 3.16–17.66, HRadj 3.22 [95% CI 2.13–4.86], and HRadj 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.

AB - 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 [HRadj] 7.47, 95% confidence interval [CI] 3.16–17.66, HRadj 3.22 [95% CI 2.13–4.86], and HRadj 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.

KW - Biomarkers

KW - Clinical trials

KW - Heart failure

KW - Natriuretic peptides

KW - Obesity

KW - Risk stratification

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DO - 10.1002/ejhf.3118

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SN - 1388-9842

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

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