Watch the full episode and view show notes here: http://bit.ly/3XZt1gC Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Dan Rader is a Professor at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis with a particular focus on the function of high-density lipoproteins (HDLs). In this episode, Dan goes in-depth on HDL biology, including the genesis of HDL, its metabolism, function, and how this relates to atherosclerotic cardiovascular disease (ASCVD). He explains why having high HDL-C levels does not directly translate to a low risk of cardiovascular disease and reveals research pointing to a better way to measure the functionality of HDL and predict disease risk. He also goes into detail on the role of HDL in reverse cholesterol transport and the benefits this has for reducing ASCVD. Additionally, Dan discusses the latest thinking around the association between HDL cholesterol and neurodegenerative diseases and ends the conversation with a discussion of how the latest research on HDL provides a promising outlook for ongoing trials and future therapeutic interventions. We discuss: -The lipidology of apoB and apoA [4:00]; -A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30]; -How the lipoprotein system differs in humans compared to other mammals [20:00]; -Clarifying the terminology around HDL and apoA [25:30]; HDL metabolism [31:45]; -CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45]; -Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30]; -SR-B1: an HDL receptor important for cholesterol efflux [48:00]; -The association between HDL levels and atherosclerosis: are they causally linked? [53:15]; -How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00]; -Disappointing results from the studies of niacin—a drug that raises HDL-C and lowers apoB [1:08:15]; -HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00]; -Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00]; -A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45]; -The association between HDL cholesterol and neurodegenerative diseases [1:34:00]; -Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45]; and -More -------- 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 45 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). Learn more: https://peterattiamd.com Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies.