#238 – AMA #43: Understanding apoB, LDL-C, Lp(a), and insulin as risk factors for cardiovascular disease | The Peter Attia Drive

Intro

In this episode of “The Peter Attia Drive,” Dr. Peter Attia dives into a deep discussion about the risk factors for cardiovascular disease, focusing on APOB, LDL-C, Lp(a), and insulin. He explores how these factors collectively influence the development and progression of atherosclerotic cardiovascular disease (ASCVD). Through a comprehensive analysis of the latest research and insights, Dr. Attia seeks to provide a better understanding of these risk factors and their implications for overall health.

Main Takeaways

Understanding Risk Factors for ASCVD

• The number one leading killer in the US and worldwide for men and women is atherosclerotic cardiovascular disease (ASCVD).
• Hyperinsulinemia increases the risk of ASCVD, but the question is whether that risk still exists once APOB is corrected.
• Mendelian randomization tells us about lifetime risk reduction of AACVD in the context of low APO-B.
• APOB, Lp(a), and insulin can collectively influence the risk of ASCVD.
• Questions around how to think about risk when APOB is low but Lp(a) is high, or when insulin is good but LDL or APOB is raised, are addressed in this episode.

Analogies for Understanding Risk Factors

• APOB and LP little a levels impact the maintenance throttle of the pedal in the race car analogy for cardiovascular disease.
• Lowering APOB levels is like pressing harder on the brake pedal to slow down the car’s progress towards death.
• Hyperinsulinemia presses harder on the throttle and accelerates the drive towards the cliff.

Significant Factors in Cardiovascular Disease

• Smoking, hypertension, and high APOB levels are the big three drivers of cardiovascular disease.
• Lowering high blood pressure is a significant way to slow down the progress towards death.
• The risk and how you think about risk is dependent on your age and the time you have to make interventions.
• No matter what age you are, you need to care about your health and lipid parameters.

Understanding APOB and LDL-C

• LDL-C is a laboratory measurement that measures the concentration of cholesterol contained within the LDL particles.
• APOB is a better predictor of risk because it captures not only the concentration of LDL but also the other atherogenic particles.
• Apob-bearing particles, like VLDL, are the most common chaperones for moving cholesterol, but they are very atherogenic and can become pathogenic if they stick around for too long.
• Increasing expression of ApoC3 and blocking lipoprotein lipase leads to an increase in triglycerides and triglyceride-rich LDLs, which can increase the concentration of apob, a risk factor for ASCVD.

The Role of Insulin in ASCVD

• Insulin, especially hyperinsulinemia, plays a role in endothelial dysfunction, which is an important risk factor for ASCVD because it allows apob particles to easily get through gaps in the endothelium and into the subendothelial space.
• Endothelial dysfunction leads to a cascade of events that increases the risk of ASCVD, and insulin seems to drive this dysfunction.
• OGTT test is a good way to check for insulin levels and potential risk factors for ASCVD.

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Disclaimer

• Disclaimer: podcast is for general informational purposes only and does not constitute medical advice.

Summary

Understanding Risk Factors for ASCVD

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Hyperinsulinemia, APOB, Lp(a), and insulin collectively influence the risk of ASCVD. Mendelian randomization provides insights into the lifetime risk reduction of ASCVD in the context of low APO-B. This episode addresses the complexities of risk assessment when APOB is low but Lp(a) is high, or when insulin levels are good but LDL or APOB is raised.

Analogies for Understanding Risk Factors

Analogies of a race car’s throttle and brake pedal are used to explain the impact of APOB and LP little a levels on the maintenance throttle and the effect of lowering APOB levels as pressing harder on the brake pedal to slow down disease progression. Conversely, hyperinsulinemia is likened to pressing harder on the throttle, accelerating the drive towards cardiovascular disease.

Significant Factors in Cardiovascular Disease

Smoking, hypertension, and high APOB levels are identified as the major drivers of cardiovascular disease. Lowering high blood pressure is a significant intervention to slow down disease progression. The understanding of risk is influenced by age, emphasizing the importance of caring about health and lipid parameters at any age.

Understanding APOB and LDL-C

LDL-C measures cholesterol concentration within LDL particles, while APOB captures not only LDL but also other atherogenic particles. Apob-bearing particles, like VLDL, can become pathogenic if they persist. Increasing expression of ApoC3 and blocking lipoprotein lipase can raise APOB levels, increasing the risk of ASCVD.

The Role of Insulin in ASCVD

Insulin, especially hyperinsulinemia, contributes to endothelial dysfunction, allowing atherogenic particles to penetrate the endothelium and increase the risk of ASCVD. The OGTT test is a useful tool to assess insulin levels and potential risk factors for ASCVD.

Membership Benefits

The membership program offers exclusive content, comprehensive show notes, a private podcast feed, and discount codes. Members gain access to the full version of the AMA on the member-only podcast feed.

Conclusion

This episode of “The Peter Attia Drive” provides valuable insights into the risk factors for cardiovascular disease, including APOB, LDL-C, Lp(a), and insulin. By understanding these factors and their interplay, individuals can make informed decisions to mitigate their risk and prioritize their cardiovascular health.