Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction

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-def...

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Vydáno v:	Scientific reports Ročník 14; číslo 1; s. 20694 - 11
Hlavní autoři:	Culler, Kasen L., Sinha, Arjun, Filipp, Mallory, Giro, Pedro, Allen, Norrina B., Taylor, Kent D., Guo, Xiuqing, Thorp, Ed, Freed, Benjamin H., Greenland, Philip, Post, Wendy S., Bertoni, Alain, Herrington, David, Gao, Chen, Wang, Yibin, Shah, Sanjiv J., Patel, Ravi B.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 05.09.2024 Nature Publishing Group Nature Portfolio
Témata:	692/4019 692/4019/592/2727 692/4019/592/75/230 Aged Aged, 80 and over Amino acids Arteriosclerosis Biomarkers - blood Brain natriuretic peptide Cardiac structure Carnitine Comorbidity Congestive heart failure Diabetes mellitus Echocardiography Female Genetic analysis Genetic diversity Genetic variance Genetics Glucose metabolism Heart diseases Heart failure Heart Failure - genetics Heart Failure - metabolism Humanities and Social Sciences Humans Inositol Inositol - metabolism Male Mannose Metabolic pathways Metabolism Metabolites Metabolome Metabolomics Metabolomics - methods Middle Aged multidisciplinary Natriuretic peptide Natriuretic Peptide, Brain - blood Natriuretic Peptide, Brain - metabolism Peptide Fragments - blood Peptides Science Science (multidisciplinary) Stroke Volume Structure-function relationships Heart failure Metabolomics Cardiac structure Echocardiography Myo-inositol Natriuretic peptide Genetics
ISSN:	2045-2322, 2045-2322
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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 1 H-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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-71329-y