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. 2022 Jun 1;7(6):623-631.
doi: 10.1001/jamacardio.2022.0680.

Sex and Race Differences in N-Terminal Pro-B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community

Peder L Myhre  1   2 , Brian Claggett  1 , Bing Yu  3 , Hicham Skali  1 , Scott D Solomon  1 , Helge Røsjø  2 , Torbjørn Omland  2 , Kerri L Wiggins  4 , Bruce M Psaty  4   5   6 , James S Floyd  4 , Elizabeth Selvin  7 , Christie M Ballantyne  8 , Amil M Shah  1
Affiliations

Sex and Race Differences in N-Terminal Pro-B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community

Peder L Myhre et al. JAMA Cardiol. .

Abstract

Importance: Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute-as opposed to relative-risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear.

Objective: To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups.

Design, setting, and participants: In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12 750 participants) and late life (visit 5; a total of 5191 participants).

Exposures: NT-proBNP concentration.

Main outcomes and measures: Incident HF or death.

Results: Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study.

Conclusions and relevance: In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Myhre has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute, and South-Eastern Norway Health Authorities; personal fees from Novartis, Amgen, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, and Bayer; and served on advisory boards for Novartis and Novo Nordisk. Dr Claggett reported personal fees from Amgen, Boehringer Ingelheim, Corvia, Cardurion, MyoKardia, and Novartis outside the submitted work. Dr Skali received consultant fees from Astellas. Dr Solomon received grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos; and consulting fees from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche Diagnostics, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. Dr Røsjø has received speaker honoraria from Novartis and consultancy honoraria from SpinChip Diagnostics and Cardinor AS. Dr Omland has received grants and personal fees from consultancy and/or speaker honoraria from Abbott Diagnostics, Roche Diagnostics, and Novartis, and has received research support from AstraZeneca, Abbott Diagnostics, Novartis, Roche Diagnostics, Thermo Fisher, Singulex, and Biomedica via Akershus University Hospital. Dr Wiggins received grants from the National Institutes of Health. Dr Psaty received grants from the National Institutes of Health and serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr Selvin received grants from the National Institute of Health. Dr Ballantyne is a holder of a provisional patent (61721475) filed by Baylor College of Medicine and Roche, has received grants from the National Institutes of Health, and nonfinancial support from Roche Diagnostics. Dr Shah received research support from Novartis and consulting fees from Philips Ultrasound, grants from the National Institutes of Health, and serves on advisory board and received personal fees from Philips Ultrasound and Johnson & Johnson. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between N-Terminal Pro–B-type Natriuretic Peptide (NT-proBNP) and Race and Sex
Abbreviations: ADI, area deprivation index; BMI, body mass index; eGFR, estimated glomerular filtration rate; GLS, global longitudinal strain; LAVi, left atrial volume index; LV, left ventricle; LVEDVi, left ventricle end-diastolic volume index; LVEf, left ventricle ejection fraction; LVMi, left ventricle mass index; LVWT, left ventricle wall thickness.
Figure 2.
Figure 2.. Median (IQR) Concentrations of N-Terminal Pro–B-type Natriuretic Peptide (NT-proBNP) in Sex- and Race-Based Categories in Midlife and Late Life
Figure 3.
Figure 3.. Predicted Risk of Heart Failure (HF) or Death in Midlife and Late Life by N-Terminal Pro–B-type Natriuretic Peptide (NT-proBNP) Concentrations Among Sex- and Race-Based Categories
A, The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 5% was 24 (15-35) and NT-proBNP was 14 pg/mL among Black men; 72 (43-101) and 69 pg/mL among Black women; 51 (41-58) and 49 pg/mL among White men; and 205 (170-255) and 200 pg/mL among White women, respectively. The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 10% was 76 (53-107) and NT-proBNP was 70 pg/mL among Black men; 188 (142-250) and was 177 pg/mL among Black women; 116 (95-125) and 109 pg/mL among White men; and 402 (312-597) and 388 pg/mL among White women, respectively. The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 20% was 252 (177-386) and NT-proBNP was 213 pg/mL among Black men; 488 (353-758) and 419 pg/mL among Black women; 273 (209-281) and 241 pg/mL among White men; and 813 (557-1744) and 724 pg/mL among White women, respectively. B, The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 10% was 31 (14-56) and NT-proBNP was 31 pg/mL among Black men; 86 (55-121) and NT-proBNP was 80 pg/mL among Black women; 87 (67-108) and NT-proBNP was 81 pg/mL among White men; and 141 (112-171) and NT-proBNP was 131 pg/mL among White women, respectively. The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 20% was 103 (62-158) and NT-proBNP was 89 pg/mL among Black men; 245 (176-365) and NT-proBNP was 208 pg/mL among Black women; 238 (198-284) and NT-proBNP was 205 pg/mL among White men; and 410 (339-516) and NT-proBNP was 350 pg/mL among White women. The NT-proBNP concentration (95% CI) associated with 5-year risk of heart failure or death at 30% was 209 (137-365) and NT-proBNP was 165 pg/mL among Black men, 451 (317-863) and NT-proBNP was 369 pg/mL among Black women, 445 (367-558) and NT-proBNP was 353 pg/mL among White men, and 798 (609-1167) and NT-proBNP was 625 pg/mL among White women.
Figure 4.
Figure 4.. Predicted 5-Year Risk of Heart Failure or Death Across Different Ages and in N-Terminal Pro–B-type Natriuretic Peptide (NT-proBNP) Concentrations for Each Demographic Subgroup
See this image and copyright information in PMC

Comment in

  • Who Is at Risk for Heart Failure?
    Yancy CW, Khan SS. Yancy CW, et al. JAMA Cardiol. 2022 Jun 1;7(6):632. doi: 10.1001/jamacardio.2022.0689. JAMA Cardiol. 2022. PMID: 35475897 No abstract available.

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