Do triglyceride-rich lipoproteins cause heart attack?

We have utilized gene variants to show that beyond LDL cholesterol, plasma triglyceride-rich lipoproteins likely represent causal factors for MI. ┬áTriglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We mapped 185 common variants for plasma lipids and across these variants, we observed that the strength of a variant’s effect on plasma triglycerides is highly correlated with the magnitude of its effect on CAD, even after accounting for potential effects of each variant on LDL cholesterol and/or HDL cholesterol. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.