NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure

Isaac R. Whitman; Eric Vittinghoff; Christopher R. DeFilippi; John S. Gottdiener; Alvaro Alonso; Bruce M. Psaty; Susan R. Heckbert; Ron C. Hoogeveen; Dan E. Arking; Elizabeth Selvin; Lin Y. Chen; Thomas A. Dewland; Gregory M. Marcus

doi:10.1161/JAHA.118.010868

NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure

Isaac R. Whitman, Eric Vittinghoff, Christopher R. DeFilippi, John S. Gottdiener, Alvaro Alonso, Bruce M. Psaty, Susan R. Heckbert, Ron C. Hoogeveen, Dan E. Arking, Elizabeth Selvin, Lin Y. Chen, Thomas A. Dewland, Gregory M. Marcus

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

12 Scopus citations

Abstract

Background-Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results-We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NTproBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT-proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT-proBNP (CHS: 40% higher than blacks; 95% CI, 29-53; ARIC: 39% higher; 95% CI, 33-46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31-1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57-2.27). NT-proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2- 69.2%; ARIC: 24.6%; 95% CI, 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94-1.23), CHF-related mediation analyses were not performed. Conclusions-A substantial portion of the relationship between race and AF was statistically explained by baseline NT-proBNP levels. No consistent relationship between race and CHF was observed.

Original language	English (US)
Article number	e010868
Journal	Journal of the American Heart Association
Volume	8
Issue number	7
DOIs	https://doi.org/10.1161/JAHA.118.010868
State	Published - 2019
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). Additional support was provided by grant N01HC35129 (Gottdiener). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract Nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN26820 1700005I. Dr Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Reagents for the NT-proBNP assays were donated by the Roche Diagnostics Corporation. Additional support was provided by the American Heart Association through grant 16EIA26410001 to Dr Alonso.

Publisher Copyright:
© 2019 The Authors.

Keywords

Atrial fibrillation arrhythmia
Congestive heart failure
Mechanisms
Mediation
NT-proBNP
Natriuretic peptide

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Whitman, I. R., Vittinghoff, E., DeFilippi, C. R., Gottdiener, J. S., Alonso, A., Psaty, B. M., Heckbert, S. R., Hoogeveen, R. C., Arking, D. E., Selvin, E., Chen, L. Y., Dewland, T. A., & Marcus, G. M. (2019). NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure. Journal of the American Heart Association, 8(7), Article e010868. https://doi.org/10.1161/JAHA.118.010868

Whitman, IR, Vittinghoff, E, DeFilippi, CR, Gottdiener, JS, Alonso, A, Psaty, BM, Heckbert, SR, Hoogeveen, RC, Arking, DE, Selvin, E, Chen, LY, Dewland, TA & Marcus, GM 2019, 'NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure', Journal of the American Heart Association, vol. 8, no. 7, e010868. https://doi.org/10.1161/JAHA.118.010868

@article{5b0197dc25814c20a47d0a358c538155,

title = "NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure",

abstract = "Background-Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results-We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NTproBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT-proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT-proBNP (CHS: 40% higher than blacks; 95% CI, 29-53; ARIC: 39% higher; 95% CI, 33-46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31-1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57-2.27). NT-proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2- 69.2%; ARIC: 24.6%; 95% CI, 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94-1.23), CHF-related mediation analyses were not performed. Conclusions-A substantial portion of the relationship between race and AF was statistically explained by baseline NT-proBNP levels. No consistent relationship between race and CHF was observed.",

keywords = "Atrial fibrillation arrhythmia, Congestive heart failure, Mechanisms, Mediation, NT-proBNP, Natriuretic peptide",

author = "Whitman, {Isaac R.} and Eric Vittinghoff and DeFilippi, {Christopher R.} and Gottdiener, {John S.} and Alvaro Alonso and Psaty, {Bruce M.} and Heckbert, {Susan R.} and Hoogeveen, {Ron C.} and Arking, {Dan E.} and Elizabeth Selvin and Chen, {Lin Y.} and Dewland, {Thomas A.} and Marcus, {Gregory M.}",

note = "Funding Information: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). Additional support was provided by grant N01HC35129 (Gottdiener). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract Nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN26820 1700005I. Dr Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Reagents for the NT-proBNP assays were donated by the Roche Diagnostics Corporation. Additional support was provided by the American Heart Association through grant 16EIA26410001 to Dr Alonso. Publisher Copyright: {\textcopyright} 2019 The Authors.",

year = "2019",

doi = "10.1161/JAHA.118.010868",

language = "English (US)",

volume = "8",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "7",

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TY - JOUR

T1 - NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure

AU - Whitman, Isaac R.

AU - Vittinghoff, Eric

AU - DeFilippi, Christopher R.

AU - Gottdiener, John S.

AU - Alonso, Alvaro

AU - Psaty, Bruce M.

AU - Heckbert, Susan R.

AU - Hoogeveen, Ron C.

AU - Arking, Dan E.

AU - Selvin, Elizabeth

AU - Chen, Lin Y.

AU - Dewland, Thomas A.

AU - Marcus, Gregory M.

N1 - Funding Information: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). Additional support was provided by grant N01HC35129 (Gottdiener). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract Nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN26820 1700005I. Dr Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Reagents for the NT-proBNP assays were donated by the Roche Diagnostics Corporation. Additional support was provided by the American Heart Association through grant 16EIA26410001 to Dr Alonso. Publisher Copyright: © 2019 The Authors.

PY - 2019

Y1 - 2019

N2 - Background-Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results-We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NTproBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT-proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT-proBNP (CHS: 40% higher than blacks; 95% CI, 29-53; ARIC: 39% higher; 95% CI, 33-46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31-1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57-2.27). NT-proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2- 69.2%; ARIC: 24.6%; 95% CI, 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94-1.23), CHF-related mediation analyses were not performed. Conclusions-A substantial portion of the relationship between race and AF was statistically explained by baseline NT-proBNP levels. No consistent relationship between race and CHF was observed.

AB - Background-Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results-We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NTproBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT-proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT-proBNP (CHS: 40% higher than blacks; 95% CI, 29-53; ARIC: 39% higher; 95% CI, 33-46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31-1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57-2.27). NT-proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2- 69.2%; ARIC: 24.6%; 95% CI, 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94-1.23), CHF-related mediation analyses were not performed. Conclusions-A substantial portion of the relationship between race and AF was statistically explained by baseline NT-proBNP levels. No consistent relationship between race and CHF was observed.

KW - Atrial fibrillation arrhythmia

KW - Congestive heart failure

KW - Mechanisms

KW - Mediation

KW - NT-proBNP

KW - Natriuretic peptide

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NT-proBNP as a mediator of the racial difference in incident atrial fibrillation and heart failure

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