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
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.
Association for ApoB
- In the primary prevention cohort, each 1 SD higher apoB was associated with 38% increase in risk of MI (aHR 1.38, 95%CI: 1.34-1.42, P<0.001).
- After full adjustment for lipid parameters (including TG, non-HDL-c and HDL-c), the association between apoB and risk of MI was maintained (HR 1.27, 95%CI: 1.15-1.40, P<0.001).
- Same patterns for apoB with risk of MI was seen in the secondary prevention cohort.
Association for non-HDL-c and TG
- Non-HDL-c was similarly associated with MI, also after adjustment for TG, but no longer when adjusted for apoB.
- Same patterns for non-HDL-c with risk of MI was seen in the secondary prevention cohort.
- In the primary prevention cohort, with each 1-SD increase, TG was associated with 16% higher risk of MI (aHR 1.16, 95%CI:1.13-1.19, P<0.001).
- There was no longer an association between TG and risk of MI after adjustment for all clinical and lipid parameters.
- In the secondary prevention cohort, TG was not associated with risk of MI.
Association for type of lipoprotein
- In the primary prevention cohort, there was no association between the ratio of lipoprotein types (TG/LDL-c ratio) and MI, indicating that for a given number of apoB-containing lipoproteins, one type is not associated with a greater risk than the other.
- The flat association between TG/LDL-c ratios and MI risk was also see in the secondary prevention group (up to TG/LDL-c ratio of 2).
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”.