View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Ethan Weiss is a preventative cardiologist at UCSF, an entrepreneur-in-residence at Third Rock Ventures, where he is working on a project related to cardiometabolic disease, and a previous guest on The Drive. In this episode, Ethan compares and contrasts the diagnostic imaging tools, CAC (coronary artery calcium score) and CTA (CT angiography), used to image plaque—including the latest in CTA software—and how these tools inform our understanding of ASCVD risk and guide clinical decision-making. Ethan discusses the types of plaque that cause events and the data that make a case for optimal medical therapy over stenting outside of particular cases. He explains why high blood pressure is problematic and walks through the data from clinical trials testing aggressive treatment. He talks about the best way to actually measure blood pressure, why we shouldn’t simply accept that blood pressure rises with age, and how he uses different pharmaceutical agents to treat hypertension. Additionally, Ethan explains our current, but limited, understanding of the role of metabolic health in ASCVD. He discusses the impact of fat storage capacity and the location of fat storage and explains how and why there is still a residual risk, even in people who have seemingly normal lipids, don't smoke, and have normal blood pressure. We discuss: Ethan’s entrepreneurial work in the cardiometabolic disease space [4:30]; Calcium scans (CAC scores) and CT angiography (CTA), and how it informs us about ASCVD risk [6:00]; Peter’s historical CAC scores, CTA results, and how one can be misled [10:45]; How Peter’s CTA results prompted him to lower his apoB [14:45]; Calcium scans vs. CT angiogram (CTA) [21:15]; How Ethan makes clinical decisions based on CTA results and plaque burden, and the importance of starting treatment early to prevent ASCVD [28:15]; Improved methods of CTA to grade plaque lesions and how it’s shaped medical decisions such as stenting [33:45]; Why Ethan favors optimal medical therapy over stenting outside of particular situations [41:45]; The need for FFR CTA, and the potential for medical therapy to eliminate ASCVD [54:00]; The fat attenuation index (FAI) and other ways to measure inflammation in a plaque [57:30]; Statins and exercise may increase the risk of calcification, but what does this mean for risk? [59:45]; The root cause of statin hesitation despite evidence that statins are a profoundly important intervention [1:05:30]; Importance of keeping blood pressure in check, defining what’s normal, and whether we should just accept higher blood pressure with age [1:10:45]; Blood pressure variability, how to best measure it, and data suggesting the enormous impact of keeping blood pressure down [1:21:00]; Drugs for treating high blood pressure recommended by the ALLHAT trial [1:35:15]; What the SPRINT trial says about the aggressive treatment of hypertension, and the risks of such treatment [1:38:15]; Confirmatory results in the STEP trial for blood pressure, and how Ethan uses the various pharmacological agents to lower blood pressure in patients [1:43:15]; The role metabolic health in ASCVD: what we do and don’t know [1:51:00]; The impact of fat storage capacity and the location of fat storage on metabolic health and coronary artery disease [1:56:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.” If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #45 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss [2:30]; Overview of GLP-1 agonists and why these drugs are getting so much attention [6:15]; Defining the term “geroprotective” [13:30]; Semaglutide: background, brand names, indications, and more [15:15]; Tirzepatide: background, brand names, indications, and more [19:15]; How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics [23:45]; Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide [29:00]; What happens to body weight when a patient discontinues the medication? [34:45]; Noteworthy side effects of GLP-1 agonists and similar classes of drugs [40:45]; Increased resting heart rate and other concerning trends in patients using GLP-1 agonists [45:15]; Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists [50:45]; Possible reasons for the loss of lean muscle mass and tips for protecting lean mass [59:00]; GLP-1 agonists and thyroid cancer [1:01:30]; Who might be a candidate for GLP-1 agonists? [1:03:45]; The large financial cost of this class of drugs [1:08:30]; Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients [1:11:30]; A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics [1:21:00]; Peter’s current approach with metformin for his patients [1:25:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Lewis Howes is a New York Times best-selling author, entrepreneur, speaker, and host of the popular podcast, The School of Greatness. In this episode, Lewis opens up about the various hardships and traumatic events he experienced starting at a very young age and reveals the valuable lessons he learned as he worked through those traumas to improve his emotional health. He talks about how his past hardships likely contributed to his success in business and athletics, only to leave him feeling unsatisfied and unfulfilled. Next, he discusses how many aspects of his life were suffering, the inflection point that drove Lewis to seek help, and the long but beautiful healing journey that followed. Lewis makes the case that adversity, and even trauma, can be beneficial if one finds meaning in tribulations and has the courage to face one’s fears and insecurities. Finally, Lewis shares the many modalities of therapy that helped him along the way and gives advice for those wanting to find inner peace and live a fulfilling, rich, abundant, joyful life. We discuss: Lewis’s upbringing and the impact of his older brother going to prison [2:45]; Finding lessons in tragedy and adversity [10:45]; Lasting trauma from being sexually abused at age 5 [13:15]; Inflection point that drove Lewis to seek help, and a beautiful experience at a therapeutic workshop [16:45]; A powerful workshop on emotional intelligence jump started Lewis’s healing journey [27:30]; How being authentic can strengthen bonds with family and bring inner peace [39:30]; Comparing adversity with trauma and finding meaning in struggle [45:15]; Association between adverse childhood events and diseases in adulthood [56:15]; How addressing his issues with intimate relationships helped Lewis overcome physical pain related to his past trauma [59:15]; Healing is a journey that takes time and requires courage to face your fears and insecurities [1:08:45]; How Lewis thinks about mortality and uses it as motivation to pursue his dreams [1:13:00]; How anyone can benefit from therapy or coaching, and Lewis’s advice for finding inner peace [1:22:45]; Lewis’s newest book, The Greatness Mindset [1:29:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Siddhartha Mukherjee is an oncologist, Pulitzer Prize-winning author, and previous guest on The Drive. In this episode, Sid discusses many of the subjects of his latest book, The Song of the Cell, including the incredible discovery of the cell and how it transformed medicine. He explains the evolutionary drive to go from single-cell to multicellular life and unpacks the four different types of cell-based therapies and the problems they are attempting to solve. He also provides the latest in gene therapy, such as CRISPR, and the ethical questions around human gene editing. Additionally, he touches on a number of fascinating topics, such as the challenges of medical science, the human brain, learning styles, his writing process, mental health, and more. We discuss: How the cell brings the genome to life, and how Sid’s recent book fits into his prior work to tell a story [2:30]; How the germ theory of disease and an understanding of the cell fueled a big leap in medicine [9:45]; What is the evolutionary drive for multicellular life? [17:15]; Four types of cell therapies and the challenges of gene therapy [26:00]; CAR T-cell therapy: promising gene therapy for cancer [36:30]; The possibility of using gene therapy to treat germline mutations like sickle cell disease [41:45]; The incredible revolution of gene editing with CRISPR [45:15]; Ethical questions around human gene editing [52:30]; The complex role of genetics in mental illness [1:01:30]; Two types of problems in science: the “eye in the sandstorm” problem and the “sand in the eye” problem [1:06:15]; Understanding neural networks: an example of the “sand in the eye” problem being solved [1:08:45]; Importance of learning by doing: comparing the learning styles of a doctoral student to a medical student [1:16:30]; Sid’s unique and brilliant style of writing [1:20:45]; Falling as the leading cause of accidental death: a liability of multicellular existence [1:25:00]; Sid’s struggle with depression and his desire to change the stigma around mental illness [1:29:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Anthony Hipolito is a sheriff’s deputy in Hays County, Texas with over 24 years of experience in law enforcement. In this episode, Anthony discusses his work to spread awareness about illicit fentanyl use and the drastic increase in accidental overdoses, especially in young people. Anthony explains the deadly nature of fentanyl, including how many counterfeit drugs are now being laced with deadly doses of fentanyl. He breaks down how fentanyl is being brought to the US and how younger and younger kids are being targeted. Additionally, Anthony discusses his goal of spreading awareness to our communities and provides important advice for what parents can do. We discuss: Anthony’s life of service in law enforcement [5:30]; Fentanyl: medical use, recreational use, and the recent rise in prevalence [8:30]; The story of a teenager dying from an accidental overdose of fentanyl [16:30]; The scope of deaths being caused by accidental overdoses (the majority of which are from fentanyl) [23:00]; How young kids are being targeted, and how fentanyl makes it across our borders and gets distributed [28:30]; What happens to a person when they overdose [35:30]; Whether laws around drug possession are helping or hurting, and the need to focus on helping people that feel the need to take these counterfeit drugs [37:00]; How fentanyl is being added to all kinds of drugs that you wouldn’t expect [42:45]; What can we do as parents? [47:15]; Narcan: a treatment for opioid overdoses [50:15]; Importance of awareness, having conversations with kids early in life, and other key takeaways for parents [56:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube