Plasma Metabolite Associations with Incident Heart Failure with Reduced and Preserved Ejection Fraction
Abstract
Background: Prior studies on metabolite associations with incident heart failure (HF) used billing code-based definitions and lacked the data on left ventricular ejection fraction needed to determine associations with HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction.
Objectives: Identify potentially causal plasma metabolite associations with HFrEF and HFpEF, ascertained using a validated machine learning- and natural language processing-based algorithm, in up to 38,000 individuals.
Methods: We included MGB Biobank participants who had available metabolomics data and no history of HF at baseline. The primary exposures were plasma levels of 42 metabolites measured using a H 1 nuclear magnetic resonance platform. The primary outcome was incident HF, ascertained by a validated machine learning- and natural language processing-based algorithm. Multivariable Cox proportional hazards regression to quantify the associations between a 1-SD difference in metabolite level and the time to incident HF. Mendelian randomization analysis was used test the potential causality of each metabolite-HF association.
Results: The final analytical cohort included 38,628 individuals with a mean age of 63 years (56% women). Higher plasma levels of glutamine associated with a higher risk of incident HF (HR [95% CI]: 1.21 [1.07-1.35]) while higher levels of docosahexaenoic acid (an omega-3 fatty acid) (0.85 [0.75-0.95]), phosphatidylcholines (0.85 [0.75-0.97]), phosphoglycerides (0.86…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 38,628 participants or records.
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