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Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Publication ,  Journal Article
Culler, KL; Sinha, A; Filipp, M; Giro, P; Allen, NB; Taylor, KD; Guo, X; Thorp, E; Freed, BH; Greenland, P; Post, WS; Bertoni, A; Gao, C ...
Published in: Sci Rep
September 5, 2024

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 5, 2024

Volume

14

Issue

1

Start / End Page

20694

Location

England

Related Subject Headings

  • Stroke Volume
  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Male
  • Inositol
  • Humans
  • Heart Failure
 

Citation

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Culler, K. L., Sinha, A., Filipp, M., Giro, P., Allen, N. B., Taylor, K. D., … Patel, R. B. (2024). Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction. Sci Rep, 14(1), 20694. https://doi.org/10.1038/s41598-024-71329-y
Culler, Kasen L., Arjun Sinha, Mallory Filipp, Pedro Giro, Norrina B. Allen, Kent D. Taylor, Xiuqing Guo, et al. “Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.Sci Rep 14, no. 1 (September 5, 2024): 20694. https://doi.org/10.1038/s41598-024-71329-y.
Culler KL, Sinha A, Filipp M, Giro P, Allen NB, Taylor KD, et al. Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction. Sci Rep. 2024 Sep 5;14(1):20694.
Culler, Kasen L., et al. “Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.Sci Rep, vol. 14, no. 1, Sept. 2024, p. 20694. Pubmed, doi:10.1038/s41598-024-71329-y.
Culler KL, Sinha A, Filipp M, Giro P, Allen NB, Taylor KD, Guo X, Thorp E, Freed BH, Greenland P, Post WS, Bertoni A, Herrington D, Gao C, Wang Y, Shah SJ, Patel RB. Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction. Sci Rep. 2024 Sep 5;14(1):20694.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 5, 2024

Volume

14

Issue

1

Start / End Page

20694

Location

England

Related Subject Headings

  • Stroke Volume
  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Male
  • Inositol
  • Humans
  • Heart Failure