Aspartic acid and palmitoleic acid were associated with lower coronary heart disease risk (HR 0.75 to 0.81), while isothreonic acid was associated with higher risk (HR 1.15).
Do fasting plasma metabolites predict subclinical alterations in left ventricular structure, diastolic function, and the long-term risk of incident coronary heart disease in American Indian individuals?
The identification of novel metabolites associated with left ventricular structure and diastolic function provides insights into metabolic pathways underlying subclinical cardiac changes and highlights potential early biomarkers for coronary heart disease risk stratification.
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Background Subclinical alterations in left ventricular (LV) structure, diastolic function, and metabolic disturbances are associated with coronary heart disease (CHD) risk, but their relationships remained unclear. Large‐scale longitudinal metabolomic profiling of LV measures is lacking. Methods Using untargeted metabolomics, we quantified 563 fasting plasma metabolites from 1799 American Indian individuals attending 2 exams (~5.5 years apart). We examined associations between metabolites and measures of LV structure (LV mass index, relative wall thickness), and diastolic function (peak early filling velocity to peak late filling velocity, isovolumic relaxation time, and deceleration time) using generalized estimating equation model. Findings were then replicated in an independent biracial cohort. Frailty Cox proportional hazards models were used to examine whether LV‐related metabolites are associated with the risk of CHD over a 20‐year follow‐up. Pathway enrichment analysis was performed to identify relevant metabolic pathways. Results We identified 173 metabolites (47 named; q <0.05) associated with LV structure or diastolic function in the SHFS (Strong Heart Family Study), and some metabolites were confirmed in the biracial cohort. Three metabolites were additionally associated with incident CHD. Aspartic acid and palmitoleic acid were associated with lower LV mass index and peak early filling velocity to peak late filling velocity ratio and lower CHD risk (hazard ratios HRs, 0.75 95% CI, 0.56–0.99 to 0.81 95% CI, 0.67–0.99), whereas isothreonic acid was associated with higher relative wall thickness and higher CHD risk (HR, 1.15 95% CI, 1.01–1.32). LV‐related metabolites were enriched in arginine biosynthesis, alanine–aspartate–glutamate metabolism, and starch and sucrose metabolism. Conclusions We identified metabolomic markers of LV structure and diastolic function, several of which that were independently associated with CHD risk, providing insight into metabolic pathways underlying LV subclinical changes and CHD.
Chen et al. (Thu,) reported a other. Aspartic acid and palmitoleic acid were associated with lower coronary heart disease risk (HR 0.75 to 0.81), while isothreonic acid was associated with higher risk (HR 1.15).
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