Where Should We Focus for arresting Atherosclerosis on lowering Apo-B or LDLC ? 

Historically, epidemiological studies have demonstrated an association between circulating levels of serum total cholesterol and cardiovascular risk. However, measures of cholesterol and TG provide information on the lipids in the blood and thus only indirectly on the types of lipoproteins and their composition, and not on the number of lipoproteins. There is exactly 1 apoB-100 on each of the atherogenic apoB-containing particles (LDL, IDL, and VLDL). Its measurement can be used as a surrogate for the concentration or number of atherogenic lipoprotein particles. Therefore, Nicholas A. Marston, MD, MPH and his team conducted a study to determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)–containing lipoproteins.

It was a prospective cohort analysis in which researchers included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The study participants were divided into two groups: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment. They evaluated ApoB, non–high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG levels. The major outcome assessed was incident myocardial infarction (MI).

Key Findings of the Study Were:

• Upon analysis, the researchers found that the apoB, non–HDL-C, and TG each individually were associated with incident MI in the primary prevention group. However, when assessed together, they observed that only apoB was associated (adjusted hazard ratio [aHR] 1.27) with incident MI.
• Similarly, they noted that only apoB was associated with MI in the secondary prevention cohort.
• After adjusting for apoB, they found no association between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and risk of MI, implying that for a given concentration of apoB-containing lipoproteins, the relative proportions of particle subpopulations may no longer be a predictor of risk.

The authors concluded, "In this cohort study, risk of MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). This suggests that apoB may be the primary driver of atherosclerosis and that lowering the concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies."

In the accompanying editorial comment, "...Accordingly, apoB should be the primary measure of the atherogenic risk of the apoB lipoproteins and the primary measure of the adequacy of therapy to lower the apoB lipoproteins. Using apoB is not the last step to improve clinical care, but it is an important next step. Given the totality of the evidence, to further delay introducing apoB into routine clinical care would break faith with our commitment to practice evidence-based medicine."

For further information:

DOI:10.1001/jamacardio.2021.5083