N-Terminal pro-brain natriuretic peptide and associations with brain Magnetic Resonance Imaging (MRI) features in middle age: The CARDIA brain MRI study

Ian T. Ferguson, Martine Elbejjani, Behnam Sabayan, David R. Jacobs, Osorio Meirelles, Otto A. Sanchez, Russell Tracy, Nick Bryan, Lenore J. Launer

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6 Scopus citations


Objective: As part of research on the heart-brain axis, we investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with brain structure and function in a community-based cohort of middle-aged adults from the Brain Magnetic Resonance Imaging sub-study of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Approach and results: In a cohort of 634 community-dwelling adults with a mean (range) age of 50.4 (46-52) years, we examined the cross-sectional association of NT-proBNP to total, gray (GM) and white matter (WM) volumes, abnormal WM load and WM integrity, and to cognitive function tests [the Digit Symbol Substitution Test (DSST), the Stroop test, and the Rey Auditory-Verbal Learning Test]. These associations were examined using linear regression models adjusted for demographic and cardiovascular risk factors and cardiac output. Higher NT-proBNP concentration was significantly associated with smaller GM volume (β = -3.44; 95% CI = -5.32, -0.53; p = 0.003), even after additionally adjusting for cardiac output (β = -2.93; 95% CI = -5.32, -0.53; p = 0.017). Higher NT-proBNP levels were also associated with lower DSST scores. NT-proBNP was not related to WM volume, WM integrity, or abnormal WM load. Conclusion: In this middle-aged cohort, subclinical levels of NT-proBNP were related to brain function and specifically to GM and not WM measures, extending similar findings in older cohorts. Further research is warranted into biomarkers of cardiac dysfunction as a target for early markers of a brain at risk.

Original languageEnglish (US)
Article number307
JournalFrontiers in Neurology
Issue numberMAY
StatePublished - May 7 2018

Bibliographical note

Funding Information:
This work was supported by NHLBI [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268200900041C] and the NIA [AG0005]. he Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content.

Publisher Copyright:
© 2018 Ferguson, Elbejjani, Sabayan, Jacobs, Meirelles, Sanchez, Tracy, Bryan and Launer.


  • Brain volume
  • Cognitive function
  • Heart-brain axis
  • Magnetic resonance imaging
  • Middle age
  • N-terminal pro-brain natriuretic peptide


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