I’ve been hearing a lot about apolipoprotein B (apoB) lately. It keeps popping up, but I’ve not been sure where it fits in or what I should do about it. The new Expert Clinical Consensus from the National Lipid Association now finally gives us clear guidance. 

ApoB is the main protein that is found on all atherogenic lipoproteins. It is found on low-density lipoprotein (LDL) but also on other atherogenic lipoprotein particles. Because it is a part of all atherogenic particles, it predicts cardiovascular (CV) risk more accurately than does LDL cholesterol (LDL-C). 

ApoB and LDL-C tend to run together, but not always. While they are correlated fairly well on a population level, for a given individual they can diverge; and when they do, apoB is the better predictor of future CV outcomes. This divergence occurs frequently, and it can occur even more frequently after treatment with statins. When LDL decreases to reach the LDL threshold for treatment, but apoB remains elevated, there is the potential for misclassification of CV risk and essentially the risk for undertreatment of someone whose CV risk is actually higher than it appears to be if we only look at their LDL-C. The consensus statement says, “Where there is discordance between apoB and LDL-C, risk follows apoB.”

This understanding leads to the places where measurement of apoB may be helpful:

• In patients with borderline atherosclerotic cardiovascular disease risk in whom a shared decision about statin therapy is being determined and the patient prefers not to start a statin, apoB can be useful for further risk stratification. If apoB suggests low risk, then statin therapy could be withheld, and if apoB is high, that would favor starting statin therapy. Certain common conditions, such as obesity and insulin resistance, can lead to smaller cholesterol-depleted LDL particles that result in lower LDL-C, but elevated apoB levels in this circumstance may drive the decision to treat with a statin. 
• In patients already treated with statins, but a decision must be made about whether treatment intensification is warranted. If the LDL-C is to goal and apoB is above threshold, treatment intensification may be considered. In patients who are not yet to goal, based on an elevated apoB, the first step is intensification of statin therapy. After that, intensification would be the same as has already been addressed in my review of the 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering. 

After clarifying the importance of apoB in providing additional discrimination of CV risk, the consensus statement clarifies the treatment thresholds, or goals for treatment, for apoB that correlate with established LDL-C thresholds, as shown in this table.

 Let me be really clear: The consensus statement does not say that we need to measure apoB in all patients or that such measurement is the standard of care. It is not. It says, and I’ll quote, “At present, the use of apoB to assess the effectiveness of lipid-lowering therapies remains a matter of clinical judgement.” This guideline is helpful in pointing out the patients most likely to benefit from this additional measurement, including those with hypertriglyceridemia, diabetes, visceral adiposity, insulin resistance/metabolic syndrome, low HDL-C, or very low LDL-C levels. 

In summary, measurement of apoB can be helpful for further risk stratification in patients with borderline or intermediate LDL-C levels, and for deciding whether further intensification of lipid-lowering therapy may be warranted when the LDL threshold has been reached. 

Lipid management is something that we do every day in the office. This is new information, or at least clarifying information, for most of us. Hopefully it is helpful. I’m interested in your thoughts on this topic, including whether and how you plan to use apoB measurements. For Medscape, I’m Dr Neil Skolnik.