Hyperinsulinemia is strongly associated with increased risk of cardiovascular disease and can be assessed through tests like OGTT.
APOB is a better predictor of cardiovascular risk compared to LDLC as it accounts for other atherogenic particles and may require pharmacotherapy to manage.
Deep dives
Relationship between Hyperinsulinemia and AS CBD
Hyperinsulinemia, particularly in cases of type 2 diabetes, is strongly associated with increased risk of atherosclerotic cardiovascular disease (AS CBD). Hyperinsulinemia influences AS CBD risk through various mechanisms, including the upregulation of APOC3 expression. This leads to increased triglyceride concentration and the production of triglyceride-rich LDL particles, both of which are atherogenic. Hyperinsulinemia also contributes to endothelial dysfunction, which further exacerbates AS CBD risk. Understanding insulin levels can be crucial in assessing AS CBD risk, and tests like OGTT can provide valuable insights.
The Importance of APOB and LDLC
APOB and LDLC are key lipid parameters that are closely related to AS CBD risk. APOB measures the concentration of all lipoprotein particles that carry the APOB lipoprotein, including LDL, VLDL, and LP-Lil-A. LDLC, on the other hand, measures the cholesterol concentration within the LDL particles. While LDLC is a predictor of risk, APOB is considered a better predictor since it accounts for both LDL concentration and other atherogenic particles. Controlling APOB concentration is crucial in managing AS CBD risk, and pharmacotherapy may be necessary to reduce it to physiologic levels.
The Cascading Effects of Insulin Resistance
Insulin resistance and hyperinsulinemia have cascading effects on AS CBD risk. One significant mechanism is the impact on APOC3 expression, which blocks the action of lipoprotein lipase, leading to increased triglyceride levels and the production of triglyceride-rich LDL particles. Another effect is endothelial dysfunction, which compromises the integrity of the endothelium and allows for increased infiltration of APOB particles. These mechanisms contribute to the progression of AS CBD. Understanding and managing insulin levels is crucial in mitigating these effects and reducing AS CBD risk.
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.
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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