Per-Particle Triglyceride-Rich Lipoproteins Imply Higher Myocardial Infarction Risk Than Low-Density Lipoproteins: Copenhagen General Population Study

Abstract

Objective: ApoB (Apolipoprotein B)-containing triglyceride-rich lipoproteins and LDL (low-density lipoproteins) 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 nonfasting 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, 2309 individuals developed myocardial infarction. Multivariable-adjusted hazard ratios for myocardial infarction per 1×1015 particles were higher with larger size and more triglyceride content of apoB-containing lipoproteins using ten different subfractions, ranging from 11 (95% CI, 5.6-22) for extra extra large VLDL (very-low-density lipoproteins) to 1.06 (1.05-1.07) for extra small VLDL to 1.02 (1.01-1.02) for IDL (intermediate-density lipoproteins), through to 1.01 (1.01-1.01) for small LDL. When combining the particle number of 6 VLDL subfractions and combining IDL and 3 LDL subfractions, hazard ratios for myocardial infarction per 1×1017 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. Biological implications include that VLDL particles are more atherogenic than LDL particles and clinically that VLDL and LDL should be measured separately.