Serum Metabolites and Heart Failure Risk: MESA and RS.

Area of Science:

• Cardiovascular Disease Research
• Metabolomics
• Biomarker Discovery

Background:

• The role of circulating metabolites in heart failure (HF) pathogenesis and clinical prediction is not well understood.
• Existing research lacks clarity on the utility of serum metabolites for HF risk assessment.

Purpose of the Study:

• To investigate associations between serum metabolites and incident heart failure (HF).
• To evaluate the performance of these metabolites in enhancing HF risk prediction models.

Main Methods:

• Utilized untargeted proton nuclear magnetic resonance spectroscopy to measure 23,571 serum metabolomic variables.
• Employed proportional hazards models in the MESA (discovery) and RS (replication) cohorts to assess metabolite-HF associations.
• Adjusted for cardiovascular risk factors and evaluated predictive performance using Harrell's C-statistic.

Main Results:

• Fifteen metabolites associated with incident HF in the MESA cohort, with 5 replicating in the RS cohort.
• Associations lost statistical significance after adjusting for diabetes or hypertension.
• Incorporating identified metabolites did not significantly improve the predictive accuracy of the PREVENT-HF model.

Conclusions:

• While 15 metabolites showed an association with incident HF, these links were not independent of common comorbidities like diabetes and hypertension.
• The investigated serum metabolites demonstrated minimal added value for HF risk prediction beyond established clinical risk equations.