Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Area of Science:

• Cardiovascular Medicine
• Metabolomics
• Biochemistry

Background:

• Metabolic comorbidities (obesity, diabetes) precede heart failure (HF) onset, causing subclinical cardiac changes.
• The specific metabolic pathways driving cardiac dysfunction before HF are not well understood.

Purpose of the Study:

• To identify circulating metabolites associated with cardiac structure and function in individuals at risk for HF.
• To investigate the relationship between these metabolites and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.
• To explore the role of specific metabolites in heart failure with preserved ejection fraction (HFpEF).

Main Methods:

• Utilized 1H-NMR metabolomic profiling in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n=3440).
• Assessed associations between 47 metabolites and echocardiographic measures of cardiac structure/function.
• Correlated significant metabolites with NT-proBNP levels and compared metabolite levels in HFpEF patients versus controls.
• Investigated genetic variants (mQTLs) associated with top metabolites.

Main Results:

• Ten metabolites, mainly related to glucose and amino acid metabolism, were associated with cardiac structure or function.
• Myo-inositol, glucose, dimethylsulfone, and carnitine correlated with higher NT-proBNP; d-mannose and acetone correlated with lower NT-proBNP.
• Elevated myo-inositol levels were observed in HFpEF patients compared to controls; a genetic variant linked to myo-inositol increased NT-proBNP risk.

Conclusions:

• Metabolomic profiling reveals novel metabolites linked to cardiac dysfunction in individuals at high risk for HF.
• These findings highlight potential metabolic pathways, particularly involving myo-inositol, relevant to future HF risk and HFpEF pathogenesis.