Out of tens of thousands of blood-based molecules and biomarkers, triglyceride-rich LDL molecules (LDL-TG) emerged as a direct cause of atherosclerotic coronary artery disease (ASCAD).
LDL-C and Apo-B are widely known CVD risk factors, but it’s still unclear which specific risk factors underlie atherosclerosis, and to what extent. To investigate this, the authors applied a hypothesis-free Bayesian network analysis and genetic studies to 665 patients with suspected CAD.
The authors assessed simultaneous associations between genotypes, gene expression levels, circulating biomarkers, and CT-based atherosclerosis levels, finding that…
- LDL-TG was directly upstream from atherosclerosis in the Bayesian analysis.
- LDL-TG was associated with atherosclerosis independent of well-known factors like age, sex, LDL-C and ApoB levels.
- Genetic variations that “turned off” the hepatic lipase gene correlated with LDL-TG levels and atherosclerosis.
- LDL-TG was positively linked to triglycerides, sd-LDL, and inflammatory markers.
What’s new? These findings are consistent with previous literature, but also reveal that LDL-TG has a central causal role in ASCAD, potentially as a result of abnormal hepatic lipase activity.
The study suggests that triglyceride-rich LDL particles directly cause atherosclerotic CAD. With the recent introduction of a simple and fully automated method to measure LDL-TG levels, this biomarker may become an important tool in the clinical assessment of atherosclerosis.
The analysis also showcases a promising new approach to evaluate genetic predisposition to ASCAD, and demonstrates how big “omics” data combined with AI has the potential to reveal novel treatment avenues.