#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D.
Release Date: 05/22/2023
#403 ‒ Peptides: separating scientific promise from marketing hype
The Peter Attia Drive
In this episode, Peter returns to the topic of peptides, offering a clear and accessible guide to a field surrounded by both genuine scientific promise and widespread misinformation. Peptides are increasingly marketed for everything from injury recovery and muscle growth to longevity and improved appearance, often with claims that extend far beyond the available evidence. Rather than promoting or dismissing peptides as a category, Peter presents a practical framework for evaluating any peptide: what it is, how it is supposed to work, and where the science is strong, weak, or simply absent....
info_outline
#402 ‒ NMR blood analysis: how heart disease risk, insulin resistance, inflammation, and mortality risk can be assessed from a single blood sample | Jim Otvos, Ph.D.
The Peter Attia Drive
Jim Otvos is a biophysical chemist who pioneered the use of nuclear magnetic resonance (NMR) spectroscopy to measure lipoprotein particles and developed the first FDA-cleared method for directly quantifying LDL particle number (LDL-P), a technology that has since expanded to provide broader insights into metabolic health, inflammation, insulin resistance, and mortality risk. In this episode, Jim recounts the unlikely story of transforming a flawed cancer test into a new way of measuring lipoproteins, explains what standard cholesterol tests can miss and why LDL-P and apoB can inform...
info_outline
#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcare
The Peter Attia Drive
In this episode of The Drive, Peter explores how seemingly obscure basic science discoveries have laid the foundation for some of the most important medical breakthroughs of the past half century. Rather than focusing on the clinical applications of modern therapies, he traces the fascinating stories behind the scientists, experiments, and unexpected discoveries that ultimately led to transformative drug classes, revealing how groundbreaking advances often emerge from research with no obvious clinical goal. Through these historical case studies, Peter provides a new perspective on the...
info_outline
#400 ‒ AMA #87: Environmental pollution and longevity: air pollution, noise, light, EMFs, and practical strategies to mitigate health risks
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter explores the evidence behind environmental pollution and its impact on long-term health, separating well-supported risks from less substantiated claims while providing a practical framework for deciding which exposures deserve attention. He explains what environmental pollution encompasses, where it fits within the broader hierarchy of longevity interventions, and why studying its health effects is uniquely challenging. Peter examines the evidence linking air pollution to disease and shares actionable strategies for improving indoor and...
info_outline
#399 ‒ The evolution of Alzheimer's disease and dementia care: how early detection, personalized treatment, new therapies, and a multimodal approach are changing the landscape | Gayatri Devi, M.D.
The Peter Attia Drive
Gayatri Devi is a nationally recognized neurologist specializing in memory disorders, including Alzheimer’s disease and related dementias. In this episode, Gayatri explains how to think about dementia as a spectrum—including Alzheimer’s disease, vascular dementia, Lewy body dementia, and mixed presentations—while exploring the evolving biology of amyloid, tau, and neuroinflammation and why brain pathology does not always correlate with symptoms. She discusses her approach to detecting subtle cognitive decline in high-functioning individuals, the role of biomarkers and APOE4 testing...
info_outline
Building strength and muscle mass: how to optimize training, nutrition, and more for longevity (AMA #71 rebroadcast)
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of muscle mass and strength, examining their essential roles in both lifespan and healthspan. Drawing from over 30 hours of prior discussions with experts including Layne Norton, Andy Galpin, and Mike Israetel, this episode distills the most important insights into one comprehensive and up-to-date conversation. Peter explores why muscle matters for longevity, metabolic health, and injury prevention, and clarifies the differences between muscle mass and strength, including which is more vital for aging well. He...
info_outline
#398 ‒ AMA #86: GLP-1 RAs and muscle loss: new data, better questions, and how to preserve muscle during weight loss
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter explores the effects of GLP-1 receptor agonists—including drugs such as Ozempic, Wegovy, and Zepbound—with a particular focus on their impact on muscle. He examines how much lean mass people actually lose during treatment and how those changes compare to weight loss achieved through other methods, while explaining why measurements of lean mass on DEXA scans can sometimes be misleading. Peter discusses the effects of these medications on bone mass, fracture risk, strength, and physical function, highlighting why functional outcomes may...
info_outline
#397 ‒ Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, and emerging treatments | Renato Tomioka, M.D., Ph.D.
The Peter Attia Drive
Renato Tomioka is a leading expert in reproductive medicine and gynecologic surgery whose unique skills allow him to diagnose and treat some of the most impactful yet frequently overlooked conditions affecting women’s health. In this episode, Renato explores endometriosis and adenomyosis, explaining what these conditions are, why they often go undiagnosed for years despite affecting millions of women worldwide, and how advances in MRI and specialized ultrasound are transforming diagnosis beyond traditional surgical laparoscopy. He discusses the decision-making process behind hormonal...
info_outline
#396 ‒ Breast cancer screening: understanding risk, deciding when to start and how often to screen, and choosing the right imaging strategy
The Peter Attia Drive
In this episode, Peter explores the critical topic of breast cancer screening, examining why thousands of women continue to die from breast cancer each year despite the availability of effective screening tools. He explains the strengths and limitations of current screening strategies, reviews the recommendations from major medical organizations, and discusses why screening guidance can often seem confusing or contradictory. Peter outlines a practical framework for understanding breast cancer risk and personalizing screening decisions, including when to begin screening, how frequently to...
info_outline
#395 - Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer's disease risk, and the effects of lipid-lowering therapies on brain health | Tom Dayspring, M.D.
The Peter Attia Drive
Tom Dayspring is a world-renowned lipidologist and one of the most thoughtful teachers in the field of lipid metabolism. In this episode, Tom returns to The Drive for a deep dive into the relationship between lipids and brain health, beginning with the fundamentals of cholesterol transport before exploring why the brain’s cholesterol system operates almost entirely independently from the rest of the body. Tom examines the roles of apoB, apoA-I, and especially apoE in cholesterol homeostasis, discusses how APOE genotype influences Alzheimer’s disease risk, and unpacks the complex links...
info_outlineView the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter’s Weekly Newsletter
John Kastelein is a renowned expert in lipoprotein metabolism and atherosclerotic cardiovascular disease (ASCVD) research. In this discussion, John delves deep into familial hypercholesterolemia (FH), a genetic disorder characterized by high levels of LDL cholesterol in the blood that increases the risk of developing heart disease. He covers its definition, genetic underpinnings, and clinical identification. He then explores the therapeutic options available for the prevention and treatment of cardiovascular disease, including the captivating history of CETP inhibitors. He explains the past shortcomings of previous CETP inhibitors before underscoring the compelling potential of the latest iterations, not only for cardiovascular disease but also for conditions like Alzheimer's disease and type 2 diabetes. Moreover, he unveils the intricate role of APOE, shedding light on why the APOE4 isoform codes for a protein that significantly increases the risk of Alzheimer's disease and cardiovascular disease. Concluding the discussion, John shares a profound sense of optimism, envisioning the possibility of targeted therapeutic interventions for high-risk patients in the near future.
We discuss:
- Familial hypercholesterolemia (FH): a genetic condition [4:30];
- Differentiating between phenotype and genotype when it comes to FH [9:45];
- The pathophysiology related to mutations of FH [15:30];
- Clinical presentations, physical manifestations, and diagnosis of FH [22:00];
- Why a small fraction of people with FH do not develop premature ASCVD [34:15];
- Treatment and prevention for those with FH [39:45];
- Addressing the assertion by some that elevated LDL is not casual in cardiovascular disease [52:45];
- The history of CETP inhibitors, and the role of the CETP protein [55:45];
- The thrifty gene hypothesis and why genes underlying FH may have been preserved [1:09:00];
- The compelling potential of the latest CETP inhibitor (obicetrapib) [1:13:00];
- Promising results from phase 3 trials exploring obicetrapib [1:27:45];
- Why the APOE4 allele increases the risk of Alzheimer’s disease, and the connection to blood lipids [1:41:30];
- The role of APOE in cardiovascular disease [1:51:45];
- Takeaways and looking ahead [1:57:00]; and
- More.
Connect With Peter on Twitter, Instagram, Facebook and YouTube