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#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D.

The Peter Attia Drive

Release Date: 05/22/2023

#329 ‒ Special AMA: Peter on exercise, important labs, building good habits, promising longevity research, and more show art #329 ‒ Special AMA: Peter on exercise, important labs, building good habits, promising longevity research, and more

The Peter Attia Drive

In this special episode of The Drive, Peter tackles a wide range of listener questions submitted over the past year. The discussion spans essential topics such as exercise—covering grip strength, traveling workouts, and why Peter doesn’t consider exercise an ideal weight-loss strategy—and the top biomarkers everyone should track. He also explores promising new longevity research, his evolving views on longevity, and frameworks like “objective, strategy, tactics” for personalized decision-making. The episode wraps up with insights on building good habits and a glimpse into...

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#328 - AMA #66: Optimizing nutrition for health and longevity: myth of a “best” diet, complexities of nutrition science, and practical steps for building a sustainable diet show art #328 - AMA #66: Optimizing nutrition for health and longevity: myth of a “best” diet, complexities of nutrition science, and practical steps for building a sustainable diet

The Peter Attia Drive

In this "Ask Me Anything" (AMA) episode, Peter dives deep into one of the most frequently discussed and often misunderstood topics: nutrition. From weight loss and maintenance to the intricate relationship between nutrition and exercise and body composition, Peter addresses the complexities of nutrition research and explores the perennial question of whether there is a "best diet." He provides practical insights on how to choose the right diet for your unique needs, discusses the role of protein and processed foods, and outlines the key questions to help you optimize your approach to...

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The Peter Attia Drive

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Optimizing life for maximum fulfillment | Bill Perkins (#237 rebroadcast) show art Optimizing life for maximum fulfillment | Bill Perkins (#237 rebroadcast)

The Peter Attia Drive

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The Peter Attia Drive

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The Peter Attia Drive

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The Peter Attia Drive

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The Peter Attia Drive

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The Peter Attia Drive

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#321 – Dopamine and addiction: navigating pleasure, pain, and the path to recovery | Anna Lembke, M.D. show art #321 – Dopamine and addiction: navigating pleasure, pain, and the path to recovery | Anna Lembke, M.D.

The Peter Attia Drive

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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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