Oxidative balance-related metabolite signature and incident cardiovascular disease and type 2 diabetes within the PREDIMED trial.
Leticia Goni, Gonzalo Fernández-Duval, Cristina Razquin et al.
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In 30 seconds
This analysis of high-cardiovascular-risk participants in the PREDIMED study used baseline plasma metabolomics and oxidative balance scores to derive a 21-metabolite signature, then assessed its association with incident cardiovascular disease (CVD) and type 2 diabetes (T2D) using multivariable Cox models. The baseline signature was inversely associated with both outcomes: per standard deviation, the hazard ratio was 0.70 (95% CI 0.61-0.81) for CVD and 0.70 (95% CI 0.60-0.80) for T2D. At 1 year, the association persisted for T2D but not CVD.
Key findings
- A consistent signature of 21 metabolites was selected from 388 candidates to reflect oxidative balance-related exposures.
- The baseline signature was inversely associated with incident CVD (HR per SD 0.70; 95% CI 0.61-0.81), but the 1-year association was not evident (HR 0.94; 95% CI 0.81-1.09).
- The signature was inversely associated with T2D at baseline (HR 0.70; 95% CI 0.60-0.80) and at 1 year (HR 0.84; 95% CI 0.72-0.97).
Why it matters
The findings suggest that a plasma metabolite profile may capture aspects of oxidative balance associated with future cardiometabolic disease. The differing results for CVD and T2D across measurement times underscore that associations may depend on outcome and timing, and that the signature should be interpreted as a risk-related marker rather than evidence that changing the metabolites prevents disease.
What to keep in mind
The analysis is observational within a trial population, so the reported associations do not establish causation. Participants were at high cardiovascular risk, which may limit generalisability.