A recent study explored the role of plasma metabolites in mid-life and their potential association with atherosclerotic cardiovascular disease risk.
In a study, published in EBioMedicine, investigators recruited a diverse cohort of 1,852 participants from the Heart SCORE study. They identified alpha-ketobutyrate (AKB) and 1-palmitoyl-2-linoleoyl-GPI as significantly protective against late-life atherosclerotic cardiovascular disease (ASCVD) events, including nonfatal myocardial infarction, revascularization, and cardiac mortality.
AKB was associated with an odds ratio (OR) of 0.62 (95% confidence interval [CI] = 0.49–0.80, P < .001), and 1-palmitoyl-2-linoleoyl-GPI had a similar association (OR = 0.62, 95% CI = 0.47–0.83, P < .001). The investigators emphasized the potential clinical relevance of these metabolites.
The findings were validated using data from the Atherosclerosis Risk in Communities (ARIC) study, which included 4,790 participants aged 75.5 ± 5.1 years.
Lead study author Anum Saeed, of the Heart and Vascular Institute at the University of Pittsburgh School of Medicine, and her colleagues explained that the data indicated that higher mid-life levels of three plasmalogens, two amino acid metabolites, and a bilirubin degradation product—all of which have anti-inflammatory properties—were associated with a lower risk of late-life ASCVD events and modestly improved long-term risk prediction parameters.
While both AKB and 1-palmitoyl-2-linoleoyl-GPI were found to be protective across the study cohorts, three plasmalogens and a bilirubin derivative demonstrated a protective association only in the Heart SCORE study.
These metabolites were influenced by genetic variants near the FADS1 and UGT1A1 genes, highlighting the role of genetic regulation in metabolite levels.
Participants in the Heart SCORE cohort had a mean age of 58.1 ± 7.5 years, 69.6% of whom were female and 43.6% of whom identified as Black. Metabolomic profiling was conducted using 1,228 metabolites, and logistic regression models were used to assess associations with ASCVD risk.
The validation cohort from the ARIC study, which had a mean age of 75.5 ± 5.1 years, provided an independent assessment of these associations.
"The biological plausibility of the protective role discovery of [AKB] and 1-palmitoyl-2-linoleoyl-GPI are strengthened by the validation in a separate longitudinal cohort of biracial participants and may be regulated by dietary intake," the study authors emphasized.
The study offered new insights into the relationship between mid-life metabolic profiles and long-term cardiovascular health. Further research is needed to establish causality and evaluate the therapeutic potential of these metabolites in ASCVD prevention and management.
The protective role of AKB and 1-palmitoyl-2-linoleoyl-GPI could inform future strategies for ASCVD risk stratification and intervention.
The research in this study was funded by the Pennsylvania Department of Health and the National Institutes of Health (NIH), including grants R01HL089292 and UL1 TR001857. The authors disclosed no individual conflicts of interest. The Pennsylvania Department of Health explicitly disclaimed responsibility for the analyses, interpretations, or conclusions drawn in the study.
