AMA #43: Understanding apoB, LDL-C, Lp(a), and insulin as risk factors for cardiovascular disease

We have this observation, which is people with type 2 diabetes are about twice as likely, maybe 50% to 2x likely, of developing ASCVD—and in fact, all-cause mortality.

So, what are the big three things that are driving ASCVD? Smoking, hypertension, ApoB. And then, of course, you have other things, like LP(a), hyperinsulinemia.

The observation that is unequivocal is hyperinsulinemia is associated with worse outcomes in ASCVD. The most obvious example of that is type 2 diabetes, which is just a very extreme manifestation of hyperinsulinemia.

I think the other thing where insulin, especially hyperinsulinemia, is playing a role is with endothelial dysfunction ... What is the cascade of events that leads to ASCVD? Endothelial dysfunction is an important risk factor. Why? Because if the endothelium is not working, the ApoB particles have an easier time getting through the gaps and into the sub-endothelial space.

Your LDL cholesterol concentration is a predictor of risk. The higher it is, the more likely your risk. But the ApoB is a better predictor of risk.

If we're really talking about reducing ApoB to the levels that we call physiologic, that's really going to be the application of pharmacotherapy.