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Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it’s inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides.
We discuss:
0:00:00 - Intro
0:00:08 - How Benoît came to study Lp(a)—a new marker for cardiovascular risk
0:04:43 - The relationship between Lp(a) and CVD risk
0:15:08 - What genome-wide association studies (GWAS) revealed about Lp(a)
0:21:54 - Clinical tests to measure Lp(a)
0:26:11 - The biology of Lp(a)
0:29:52 - How statins lower LDL-cholesterol and why this doesn't work for an Lp(a)
0:35:20 - The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle
0:46:00 - The role of Lp(a) in aortic valve disease
0:52:24 - How greater numbers of Lp(a) particles are associated with increased risk of disease
0:56:56 - The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels
1:07:30 - Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk
1:22:46 - Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD
1:28:36 - The variability of disease in patients with high Lp(a)
1:37:45 - Diseases most associated with high Lp(a)
1:48:05 - The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9
2:04:58 - The variability in PCSK9 inhibitors’ ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a)
2:10:38 - Peter’s approach to managing patients with high Lp(a), and Benoît’s personal approach to managing his risk
2:13:33 - Antisense oligonucleotides—a potential new therapeutic for Lp(a)
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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 40 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).
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