Apo B, a potential Lipid Predictor of MI Risk: JAMA

There has been recent debate about how much lipid-associated cardiovascular risk is from LDL cholesterol versus triglycerides. However, genetic studies suggest that apolipoprotein B is actually the primary driver of atherosclerotic risk. To further examine this, Dr Nicholas A. Marston 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.

In this prospective cohort analysis, the researchers included individuals from the population-based UK Biobank and 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. The researchers assessed two populations in this analysis:

◊ 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 the levels of ApoB, non–high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG. The major outcome assessed was incident myocardial infarction (MI).

Key findings of the study:

• Upon analysis, the researchers found that in the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI.
• However, when assessed together, they found that only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27). Also, 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, Allan Sniderman, MD, Ann Marie Navar, MD, PhD, and George Thanassoulis, MD wrote, " The debate is over.. apoB should be the primary marker to assess cardiovascular risk due to apoB lipoproteins".

They point out that LDL and non-HDL cholesterol both become insignificant markers of risk when apoB is taken into account, "demonstrating that the risk of LDL cholesterol and non-HDL cholesterol is fully captured by the number—not the cholesterol content—of the apoB-containing particles."

ApoB can also be used as an alternative to LDL cholesterol as the primary means to screen, diagnose, and manage patients, according to the guidelines of the 2019 European Society of Cardiology/European Atherosclerosis Society. However, ApoB is not currently endorsed by the US guidelines but, can be considered a "risk enhancer" if it exceeds 130 mg/dL.

For further information:

DOI: 10.1001/jamacardio.2021.5083