Per particle triglyceride-rich lipoproteins imply higher myocardial infarction risk than low-density lipoproteins: Copenhagen General Population Study

Objective: Apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins and low-density lipoproteins (LDL) are each causal for myocardial infarction and atherosclerotic cardiovascular disease; however, the relative importance is unknown. We tested the hypothesis that for the same number of apoB-containing particles from smaller LDL through to larger triglyceride-rich lipoproteins, the risk of myocardial infarction is similar.

Approach and Results: We included 29,039 individuals with no history of myocardial infarction nested within 109,751 individuals from the Copenhagen General Population Study. Particle number of apoB-containing lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy. During a mean follow-up of 10 years, 2,309 individuals developed myocardial infarction. Multivariable adjusted hazard ratios for myocardial infarction per 1∙1015 more particles were higher with larger size and more triglyceride content of apoB-containing lipoproteins using ten different subfractions, ranging from 11 (95% confidence interval, 5.6-22) for extra extra large very low-density lipoproteins (VLDL), to 1.06 (1.05-1.07) for extra small VLDL, to 1.02 (1.01-1.02) for intermediate-density lipoproteins (IDL), through to 1.01 (1.01-1.01) for small LDL. When combining the particle number of six VLDL subfractions and combining IDL and three LDL subfractions, hazard ratios for myocardial infarction per 1∙1017 more particles were 3.5 (2.7-4.5) for VLDL and 1.3 (1.2-1.4) for IDL and LDL combined.

Conclusions: For the same number of apoB-containing particles (1∙1017 particles/L), the hazard ratio for myocardial infarction was 3.5-fold for VLDL and 1.3-fold for IDL and LDL combined. These findings challenge plasma apoB and non-high-density lipoprotein cholesterol as summary indices of all apoB-containing lipoproteins.