Physicians' Academy for Cardiovascular Education

ApoB is the only independent driver of lipid-associated MI risk

Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis – Distinguishing Between Particle Concentration, Type, and Content

Literature - Marston NA, Giugliano RP, Melloni GEM et al., - JAMA Cardiol 2022, doi:10.1001/jamacardio.2021.5083

Introduction and methods


The number of atherogenic apoB-containing particles (LDL, IDL and VLDL) may be the driver of CV risk, rather than cholesterol or triglycerides (TG) content per se, as Mendelian randomization studies have shown that apoB is a better predictor of coronary artery disease than LDL-c or TG concentrations [1.2]. There is 1 ApoB-100 molecule per atherogenic apoB-containing particle, and therefore measurement of ApoB-100 can be used as surrogate for the concentration or number of atherogenic lipoprotein particles.

This study investigated the predictive value for CV risk of common measures of cholesterol concentration, TG concentration, their ratio and the number of apoB-containing lipoproteins using data from a large primary cohort and 2 secondary prevention cohorts.


A prospective cohort analysis was performed in a primary prevention group including 389.529 individuals without lipid-lowering therapy in the UK Biobank [3,4] and in a second group of 40.430 patients with established atherosclerosis disease who received lipid-lowering therapy enrolled in FOURIER [5,6] or IMPROVE-IT [7,8]. Median follow-up was 11.1 (IQR: 10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the combined clinical trial cohort.


The end point of interest was fatal of nonfatal MI.

Main results

Association for ApoB

Association for non-HDL-c and TG

Association for type of lipoprotein


This analysis showed that apoB was the only independent driver of lipid-associated MI risk, demonstrating the importance of number (concentration) of apoB-containing lipoproteins. Furthermore, the concent of lipid (cholesterol or TG) and the type (LDL or TG-rich) of apoB-containing lipoprotein particle had no additional risk beyond apoB concentration. These findings were consistent in a primary prevention and secondary prevention cohort.

The authors conclude that “lowering the overall concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies”.


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Find this article online at JAMA Cardiol

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