Metabolomic Profiles and Changes During the 20 Years Preceding Heart Failure

Area of Science:

• Cardiovascular Research
• Metabolomics
• Biomarker Discovery

Background:

• Longitudinal metabolomic studies are crucial for understanding heart failure (HF) progression.
• Identifying HF risk biomarkers enables precision prevention strategies.
• Metabolite profiles may differ across individuals with various metabolic disorders.

Purpose of the Study:

• To identify serum metabolites associated with HF risk using longitudinal metabolomic analysis.
• To delineate the dynamic trajectories of these metabolites over time.
• To explore metabolite profiles in relation to different metabolic disorders.

Main Methods:

• Analysis of longitudinal serum metabolomic data from 1728 HF-free participants over 20 years.
• Utilized intensity models and Cox proportional-hazards models to identify HF risk-associated metabolites.
• Employed latent variable mixed-effects models to evaluate metabolite trajectories.

Main Results:

• 23 serum metabolites were associated with HF risk (FDR-adjusted P<0.05), including 9 novel associations.
• Metabolites showed distinct trajectory clusters, with most HF risk-associated metabolites remaining stable or declining.
• Metabolite levels diverged >5 years before clinical HF diagnosis, with changes initiating 15-20 years prior.
• Distinct HF-associated metabolite profiles were observed in populations with hypertension, obesity, and dysglycemia, linked to specific biological pathways.

Conclusions:

• This study identifies key HF-associated metabolite profiles and their longitudinal changes.
• Metabolite alterations precede clinical HF diagnosis by up to 20 years.
• Findings highlight metabolic heterogeneity in HF risk across different comorbidities, informing future research.