Common Variants Associated With Plasma Triglycerides and Risk for Coronary Artery Disease

Are triglycerides a true cause of heart disease, or merely a bystander that travels with the real culprits? This genetic study delivered one of the clearest answers.

Using genetic variants as natural randomizers across nearly 190,000 people, the investigators showed that variants raising triglycerides increased coronary disease risk — and crucially, this held even after accounting for those variants’ effects on LDL and HDL cholesterol. The size of a variant’s effect on triglycerides tracked with its effect on heart disease. By contrast, HDL-raising variants showed no independent protective effect once other lipids were considered.

The conclusion reshaped the lipid landscape: triglyceride-rich lipoproteins — which carry apoB — are causally atherogenic, not innocent markers. It is part of the genetic case that anything carrying apoB into the artery wall contributes to disease, while it simultaneously demolished the idea that HDL is causally protective.

We rate the evidence strong. A large, rigorous Mendelian randomization and GWAS study, it provided causal-grade evidence that has helped redirect therapeutic attention toward triglyceride-rich, apoB-containing particles.