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Peter Attia MDPeter Attia MD

ApoB, LDL-C, Lp(a), and insulin as risk factors for cardiovascular disease [AMA 43 sneak peek]

Watch the full episode and view show notes here: http://bit.ly/3QBvV8R Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ 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. In this sneak peek, we discuss: 00:00 - Intro 00:08 - A racecar analogy for understanding atherosclerotic cardiovascular disease 09:15 - Defining and differentiating apoB and LDL-C 12:36 - The interrelated nature of insulin levels, apoB, triglycerides, and ASCVD parameters 18:17 - Another way that hyperinsulinemia plays a role in endothelial dysfunction In the full episode, we also discuss: -Why Peter uses the oral glucose tolerance test (OGTT) with all patients; -Is there any evidence that hyperinsulinemia is an independent contributor to ASCVD?; -Thinking through risk in the context of high-fat diets resulting in improved metabolic metrics but with an elevation of apoB/LDL-C; -Thinking through risk in the context of low apoB but higher than normal triglyceride levels; -The importance of lowering apoB for reducing ASCVD risk; -Data on men and women with familial hypercholesterolemia that demonstrates the direct impact of high apoB and LDL-C on ASCVD risk; -Importance of starting prevention early, calcium scores, and explaining causality; -Defining Lp(a), its impact on ASCVD risk, and what you should know if you have high Lp(a); -Lp(a) and ethnic differences in risk; -Why someone with elevated Lp(a) should consider being more aggressive with apoB lowering strategies; -Addressing the common feeling of hesitancy to taking a pharmacologic approach to lower ASCVD risk; -Peter’s take on the 2022 Formula 1 season and thoughts on 2023; and -More. -------- About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 45 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies.

Peter Attiahost
Jan 16, 202324mWatch on YouTube ↗

At a glance

WHAT IT’S REALLY ABOUT

Peter Attia Explains How ApoB, Lp(a), and Insulin Drive Heart Disease

  1. Attia frames ASCVD as a car heading toward a cliff, where risk factors like smoking, hypertension, apoB, Lp(a), and hyperinsulinemia press the throttle and therapies like lowering apoB press the brake.
  2. He distinguishes LDL-C (cholesterol within LDL particles) from apoB (the count of all apoB-bearing particles including LDL, VLDL, and Lp(a)) and explains why apoB is the better risk predictor and his preferred goalpost.
  3. He describes how hyperinsulinemia raises apoB by upregulating apoC-3, blocking lipoprotein lipase, raising triglycerides, and creating triglyceride-rich LDL that prompts the body to make more particles.
  4. He adds that insulin appears to drive endothelial dysfunction, making it easier for apoB particles to enter the artery wall, though this is harder to demonstrate than the apoC-3 mechanism.
  5. The host stresses that earlier action matters because a long-horizon view of risk gives more time to intervene, and that people of any age should know their apoB and Lp(a).

IDEAS WORTH REMEMBERING

5 ideas

Risk factors can be thought of as throttle and brake

Attia says the car can't be stopped, but combining less throttle (smoking, hypertension, apoB, Lp(a), hyperinsulinemia) with more brake (lowering apoB, treating blood pressure) can slow the trajectory dramatically.

Lp(a) is a fixed baseline throttle

Attia describes Lp(a) as not under your control, with people born with low levels having low maintenance throttle and those with high levels having more.

LDL-C is not the same as LDL

Attia notes LDL itself isn't a lab measurement; LDL-C measures cholesterol within particles, while LDL-P counts particles and apoB counts all atherogenic particles.

ApoB is the better predictor and treatment target

Because particle number drives risk more than cholesterol content and apoB includes VLDL and Lp(a), Attia uses apoB concentration as his goalpost, even aiming to drastically lower it to reduce residual risk.

Hyperinsulinemia raises apoB through apoC-3

Elevated insulin upregulates apoC-3, which blocks lipoprotein lipase, raises triglycerides, and produces triglyceride-rich LDL, pushing the body to make more apoB-containing particles.

WORDS WORTH SAVING

5 quotes

If you imagine your lifespan is the length of time it takes you to drive a race car from point A to point B, where point B is driving it off a cliff, and you have two feet and two pedals, right? So you have the accelerator and you have the brake, and your feet are always on both pedals.

— Peter Attia

We have a car that we can't actually stop, but we can really slow it down to a dull roar.

— Peter Attia

If you're 100 feet from the end of the cliff and you're traveling fast, you better get ready to lock up the brakes. And if you have a mile between you and the cliff, then you can be a lot more judicious in your use of the brake pedal.

— Peter Attia

We know that it's the number of particles more than the cholesterol concentration of the particles that drives risk.

— Peter Attia

Years before a person shows up at their doctor and the doctor says, "Hey, you've got type 2 diabetes," if you knew where to look, you would see hyperinsulinemia.

— Peter Attia

Race car analogy for ASCVDapoB versus LDL-CLp(a) as baseline riskHyperinsulinemia and type 2 diabetesApoC-3 and lipoprotein lipaseEndothelial dysfunctionShort-term versus long-term risk

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