ApoB more accurate than LDL or non-HDL cholesterol in predicting future MI risk, JAMA study.

There has been considerable debate whether apoB, LDL-C, or non-high-density lipoprotein cholesterol (non-HDL-C) should be the primary measure of apoB lipoprotein-related risk. Well, the debate is finally over with the results of a recent study by Marston et al that was published this week in JAMA Cardiology. The study supplies decisive evidence from a large, prospective observational study, UK Biobank, and 2 clinical trials, FOURIER and IMPROVE-IT, that apoB should be the primary marker to assess the cardiovascular risk due to the apoB lipoproteins.

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).

The idea behind this observation stems from the fact that the cholesterol content of LDL particles varies while each apoB lipoprotein particle always has fixed one apoB molecule; therefore, apoB equals atherogenic particle number. Because the mass of cholesterol per particle is variable, LDL-C and non-HDL-C can differ significantly from apoB. Thus, when cholesterol-depleted particles are present, the risk predicted by apoB will be higher than the risk predicted by LDL-C or non-HDL-C.

Mendelian randomization studies have shown that apoB is a better predictor of coronary artery disease risk than serum LDL-C or TG concentration, suggesting that the number of atherogenic particles may be the driver of cardiovascular risk, rather than cholesterol or TG content per se.

This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 years in UK Biobank and 2.5 years in the clinical trials. Two populations were studied in this analysis: the primary prevention group who were not taking lipid-lowering therapy and patients with established atherosclerosis who were receiving statin treatment. The primary study outcome was incident myocardial infarction (MI).

In the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated. Similarly, only apoB was associated with MI in the secondary prevention cohort.

Adjusting for apoB, there was 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.

Another advantage of apoB cited by Sniderman et al in an accompanying editorial is "apoB is far less prone to measurement error than LDL-C or non-HDL-C. The European Atherosclerosis Society/European Federation of Laboratory Medicine consensus report states that apoB can be measured inexpensively, and more accurately, than LDL-C or non-HDL-C, using standardized, automated, widely available methods that produce results as rapidly as a conventional lipid panel."

Does measuring apoB mean abandoning the conventional lipid panel? No. Together, apoB and a conventional lipid panel allow accurate diagnosis of all the clinically significant dyslipoproteinemias, including type III hyperlipoproteinemia.

"ApoB would certainly be easier for patients to understand than non-HDL-C: rather than discussing "bad cholesterol," we shift to discussing the "number of bad cholesterol particles", further write Sniderman et al.

ApoB can be measured directly and accurately, and better predicts risk than LDL-C or non-HDL-C. 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.

Source: JAMA Cardiology

1. doi:10.1001/jamacardio.2021.5083

2. doi:10.1001/jamacardio.2021.5080