Very low-density lipoprotein cholesterol may mediate a substantial component of the effect of obesity on myocardial infarction risk: the Copenhagen General Population Study

Background: Plasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by respectively cholesterol and triglycerides in very low-density lipoproteins (VLDL).
Objectives: We tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins.

Methods: Nested within 109,751 individuals from the Copenhagen General Population Study, we examined 25,480 free of lipid-lowering therapy and myocardial infarction at study entry. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL).

Results: During a median of 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1 mmol/L higher levels, multivariable adjusted hazard ratios for myocardial infarction were 2.07 (95%CI: 1.81-2.36) for VLDL cholesterol, 1.19 (1.14-1.25) for VLDL triglycerides, 5.38 (3.73-7.75) for IDL cholesterol, and 1.86 (1.62-2.14) for LDL cholesterol. Per 1 g/L higher plasma apoB, the corresponding value was 2.21 (1.90-2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL+LDL cholesterol, while VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL+LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, while VLDL triglycerides did not explain risk.

Conclusion: VLDL cholesterol explained half of the myocardial infarction risk from elevated apoB-containing lipoproteins, while VLDL triglycerides did not explain risk.