#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
#347 – Peter’s takeaways on mastering sleep, dealing with chronic pain, developing breakthrough cancer drugs, transforming healthcare with AI, advancing radiation therapy, and healing trauma | Quarterly Podcast Summary #5
The Peter Attia Drive
In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions with Jeff English on the journey to healing from trauma; Ashley Mason on improving sleep and CBT-I; Sanjay Mehta on misconceptions around radiation and its use in cancer therapy and treating inflammatory conditions (such as arthritis and tendonitis); Sean Mackey on understanding and treating acute and chronic pain; and Susan Desmond-Hellmann on insights from her extraordinary career that pertain...
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#346 - Scaling biotech and improving global health: lessons from an extraordinary career in medicine | Susan Desmond-Hellmann, M.D., M.P.H.
The Peter Attia Drive
Susan Desmond-Hellmann is a physician and scientist whose remarkable career has spanned clinical medicine, oncology, biotech innovation, and global health leadership. In this episode, Susan shares insights from her journey training in internal medicine during the early AIDS crisis, treating HIV-related cancers in Uganda, and developing groundbreaking cancer therapies like Herceptin and Avastin. She reflects on her leadership roles at UCSF and the Bill and Melinda Gates Foundation, offering lessons on guiding large-scale health initiatives, navigating uncertainty, and fostering scientific...
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#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.
The Peter Attia Drive
Sean Mackey is a professor of pain medicine at Stanford University and the director of the Stanford Systems Neuroscience and Pain Lab, where his research explores the neural mechanisms of pain and the development of novel treatments for chronic pain. In this episode, Sean joins Peter for a wide-ranging discussion on the multifaceted nature of pain—as both a sensory and emotional experience—and its evolutionary purpose as a critical survival mechanism. He dives into how pain is transmitted through the nervous system, the different types of pain, and why different individuals perceive...
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#344 - AMA #70: Nicotine: impact on cognitive function, performance, and mood, health risks, delivery modalities, and smoking cessation strategies
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter dives deep into nicotine—a topic increasingly debated both scientifically and publicly. He clarifies the critical differences between nicotine and tobacco, highlighting why nicotine alone isn't primarily responsible for smoking's severe health consequences. Peter examines the specific risks associated with nicotine use, including addiction, sleep disruption, cardiovascular concerns, and effects on mood and anxiety. He evaluates various nicotine delivery methods, from traditional cigarettes to gums, pouches, and synthetic alternatives,...
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#343 – The evolving role of radiation: advancements in cancer treatment, emerging low-dose treatments for arthritis, tendonitis, and injuries, and addressing misconceptions | Sanjay Mehta, M.D.
The Peter Attia Drive
Sanjay Mehta is a radiation oncologist with over 25 years of experience, and is currently the president of Century Cancer Centers in Houston, Texas (). In this episode, Sanjay explores the rapidly evolving field of radiation oncology, addressing common misconceptions about radiation exposure. He delves into radiation’s critical role in modern oncology, examining recent advancements that precisely target tumors while minimizing damage to surrounding healthy tissues and reducing side effects, with specific insights into breast, prostate, and brain cancers. Sanjay discusses fascinating...
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#342 ‒ Aging well: Peter shares strategies for improving longevity with residents at a senior living center
The Peter Attia Drive
In this special episode of The Drive, Peter joins a unique conversation inspired by his daughter’s volunteer experience at a senior care center, where she formed meaningful relationships with residents curious about healthspan, lifespan, and strategies for living well as they age. Peter engages directly with the residents, covering critical topics like the profound impact of exercise—particularly strength training— for maintaining mobility, preventing falls, and preserving independence later in life. He also discusses the importance of nutrition, emphasizing adequate protein intake,...
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#341 - Overcoming insomnia: improving sleep hygiene and treating disordered sleep with cognitive behavioral therapy for insomnia | Ashley Mason, Ph.D.
The Peter Attia Drive
Ashley Mason is a clinical psychologist and an associate professor at UCSF, where she leads the Sleep, Eating, and Affect (SEA) Laboratory. In this episode, Ashley provides a masterclass on cognitive behavioral therapy for insomnia (CBT-I), detailing techniques like time in bed restriction, stimulus control, and cognitive restructuring to improve sleep. She explains how to manage racing thoughts and anxiety, optimize sleep environments, and use practical tools like sleep diaries to track progress. She also offers detailed guidance on sleep hygiene; explores the impact of temperature...
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#340 - AMA #69: Scrutinizing supplements: creatine, fish oil, vitamin D, and more—a framework for understanding effectiveness, quality, and individual need
The Peter Attia Drive
In this "Ask Me Anything" (AMA) episode, Peter explores the complex world of supplements by introducing a practical framework for evaluating their effectiveness and relevance to individual health needs. Rather than providing a simple list of recommendations, Peter aims to equip listeners with the tools to critically assess supplements on their own. He then applies this framework to discuss research on several popular supplements, including creatine, fish oil, vitamin D, B vitamins, and ashwagandha. Additionally, he covers key factors in assessing supplement quality, helping listeners...
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#339 - Unpacking trauma: How early wounds shape behavior and the path toward healing | Jeff English
The Peter Attia Drive
Jeff English is a trauma-focused clinical counselor with extensive experience working with adults, teens, families, and groups across various settings, including career counseling, life coaching, addiction recovery, professional workshops, and private practice. In this episode, Jeff shares insights from his work as a trauma therapist, exploring how moments of perceived helplessness shape behaviors and how adaptive strategies can become maladaptive over time. He discusses the concept of the “trauma tree,” examining its roots (causes) and branches (consequences), and highlights a powerful...
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#338 ‒ Peter’s takeaways on aerobic exercise and VO2 max, insulin resistance, rising healthcare costs, treating children with autism and ADHD, and strength training | Quarterly Podcast Summary #4
The Peter Attia Drive
In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions on diverse topics such as aerobic efficiency and VO2 max with Olav Aleksander Bu; insulin resistance with Ralph DeFronzo; economics of the US healthcare system and cost-saving strategies with Saum Sutaria; diagnosis and treatment of autism, ADHD, and anxiety in children with Trenna Sutcliffe; and strength training with Mike Israetel. Additionally, Peter shares any personal behavioral adjustments...
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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.
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