Nick Stenson joins the conversation to unveil the intricacies of cardiovascular disease risk factors. They discuss the roles of apoB, LDL-C, and Lp(a) in atherosclerotic cardiovascular disease, using a racecar analogy to illustrate how lifestyle choices and metabolic markers impact health. The duo dives into the interconnection of insulin and lipid levels, emphasizing how hyperinsulinemia can worsen risks. They also highlight the importance of the Oral Glucose Tolerance Test for early diabetes detection and better insulin management.
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insights INSIGHT
ApoB vs. LDL-C
LDL-C measures cholesterol within LDL particles, while apoB measures all apoB-containing particles (LDL, VLDL, Lp(a)).
ApoB is a better predictor of ASCVD risk than LDL-C.
insights INSIGHT
Hyperinsulinemia and ASCVD Risk
Hyperinsulinemia is linked to worse ASCVD outcomes, exemplified by type 2 diabetes.
Elevated postprandial insulin is an early warning sign of insulin resistance and increased risk.
insights INSIGHT
Mechanisms of Hyperinsulinemia's Impact
Hyperinsulinemia increases ASCVD risk through two main mechanisms: APOC3 expression and endothelial dysfunction.
Increased APOC3 blocks LPL, raising triglycerides and apoB, while endothelial dysfunction eases apoB particle entry into the subendothelial space.
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In this “Ask Me Anything” (AMA) episode, Peter answers questions related to the leading cause of death in both men and women—atherosclerotic cardiovascular disease (ASCVD). He highlights the most important risk factors for ASCVD, such as apoB, LDL, hyperinsulinemia, and Lp(a), and explains the mechanism by which they confer risk and how these factors are interrelated. Peter also dives deep into the data around apoB to try to answer the question of how much residual risk is conferred for ASCVD through metabolic dysfunction once you correct for apoB. He also looks at the data around lifetime risk reduction of ASCVD in the context of low apoB.
If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #42 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
A racecar analogy for understanding atherosclerotic cardiovascular disease [2:00];
Defining and differentiating apoB and LDL-C [10:00];
The interrelated nature of insulin levels, apoB, triglycerides, and ASCVD parameters [13:00];
Another way that hyperinsulinemia plays a role in endothelial dysfunction [18:00];
Why Peter uses the oral glucose tolerance test (OGTT) with all patients [20:15];
Is there any evidence that hyperinsulinemia is an independent contributor to ASCVD? [23:00];
Thinking through risk in the context of high-fat diets resulting in improved metabolic metrics but with an elevation of apoB/LDL-C [27:30];
Thinking through risk in the context of low apoB but higher than normal triglyceride levels [32:15];
The importance of lowering apoB for reducing ASCVD risk [38:15];
Data on men and women with familial hypercholesterolemia that demonstrates the direct impact of high apoB and LDL-C on ASCVD risk [47:45];
Importance of starting prevention early, calcium scores, and explaining causality [52:30];
Defining Lp(a), its impact on ASCVD risk, and what you should know if you have high Lp(a) [56:30];
Lp(a) and ethnic differences in risk [1:00:30];
Why someone with elevated Lp(a) should consider being more aggressive with apoB lowering strategies [1:05:00];
Addressing the common feeling of hesitancy to taking a pharmacologic approach to lower ASCVD risk [1:07:15];
Peter’s take on the 2022 Formula 1 season and thoughts on 2023 [1:15:15]; and
The Peter Attia Drive 