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Peter Attia MD#52–Ethan Weiss, M.D: Cardiovascular disease and growth hormone—two surprisingly interrelated topics
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CHAPTERS
- 0:04 – 22:23
Gretzky Jerseys and Hopkins Memories
After the intro and a note on listener-supported funding, Peter and Ethan chat in Ethan's office about his signed Gretzky jersey and Peter's Oilers childhood. They then compare notes on Johns Hopkins, where Ethan grew up around the hospital, studied music at Vassar first, and endured a tough medical school start.
- •Ethan won a signed 1986 Oilers jersey at a charity auction with a minimum bid
- •Peter bought his own Oilers jersey at ten with birthday money
- •Ethan, a second-generation cardiologist, grew up around Hopkins and arrived without a science background
- •Both recall Hopkins medical school culture and Dr. Cameron's Sunday School
- •Ethan describes grueling every-other-night call in the 1990s residency
- 22:23 – 24:25
How Ethan Chose Cardiology
Ethan explains why he went into cardiology despite wanting to avoid his father's field. Young heart-attack patients without obvious risk factors, and a research year in Pascal Goldschmidt's lab, drew him in.
- •A CCU rotation exposed him to young MI patients without risk factors
- •A summer lab job on trinucleotide repeats showed him he loved research
- •He asked about the pathogenesis of unstable angina and MI in the young and was pointed to Pascal Goldschmidt
- •The lab experience drove his clinical interest more than the reverse
- 24:25 – 32:17
Plaque Rupture, Clotting, and the Cause of Heart Attacks
Ethan explains that nearly all heart attacks come from a ruptured atherosclerotic plaque rather than a pipe slowly closing. Autopsy work showed repeated rupture and healing, and Peter's epoxy analogy illustrates how tissue factor triggers clotting. They also discuss the balance of clotting and anticoagulation.
- •Almost all heart attacks come from ruptured plaques, with clots shown to be causal through autopsy and aspiration studies
- •Plaques show layered rupture and healing, like rings of a tree
- •Macrophage tissue factor exposed to blood triggers clotting, which Peter likens to two-part epoxy
- •Clotting must be fast but localized, as shown by mouse knockouts of pro- and anticoagulant genes
- 32:17 – 44:00
Defining MI, Unstable and Stable Angina
Ethan walks through the old clinical definitions of MI based on chest pain, EKG changes and biomarkers, and Q-wave versus non-Q-wave infarcts. He then explains unstable versus stable angina as a supply-demand problem, and why a 70% narrowing is where symptoms and tests become detectable but not where danger necessarily lies.
- •MI was defined by chest pain, EKG changes and enzyme leakage
- •Stable angina reflects a fixed lesion that cannot dilate when demand rises
- •Symptoms and stress tests typically appear around 70% stenosis
- •Fatal ruptures often occur in arteries with only 30–40% narrowing
- •Predicting which plaque will be the fatal one remains difficult
- 44:00 – 49:58
Modern ACS Nomenclature and Emergency Treatment
Ethan explains how the field moved to ST elevation MI, non-ST elevation ACS, and the 'time is myocardium' push to open arteries fast. They discuss door-to-balloon times and the trade-offs of quality metrics.
- •ST elevation signals complete artery blockage and triggers cath lab activation
- •Unstable angina has been folded into non-ST elevation ACS
- •ER or field teams now activate the cath lab without waiting for enzymes
- •Door-to-balloon time is a quality metric with some trade-offs
- •Primary angioplasty replaced clot-busting drugs in most US hospitals
- 49:58 – 1:06:35
The Cath Lab, Stents, and Antiplatelet Therapy
They explain what happens in a cath lab, why mechanical opening beats clot-busting drugs, and the history of stents. Ethan covers restenosis, drug-eluting stents, stent thrombosis, and why Plavix adherence matters.
- •Catheters are threaded up to the coronary ostia and a balloon opens the blockage
- •Clot-busting drugs act systemically and risk bleeding elsewhere
- •Bare metal stents suffered from restenosis; drug-eluting stents with mTOR inhibitors largely solved it
- •Drug-eluting stents slowed endothelial coverage, creating a late stent thrombosis risk
- •Ethan tells patients that taking Plavix every day after a stent is what matters most
- 1:06:35 – 1:29:33
COURAGE, ORBITA, and Stents for Stable Angina
Peter and Ethan turn to the gray area of stable angina. They cover COURAGE, which found no heart-outcome benefit from stenting over medical therapy, and the sham-controlled ORBITA, which showed little symptom benefit. They also discuss how Ethan changed his practice, and the point that symptom relief matters.
- •Only a subset benefited from bypass; stenting aimed to replicate this in stable disease
- •Benefit should be separated into symptoms versus mortality
- •COURAGE (2007) found no difference in heart outcomes between stenting and medical therapy
- •ORBITA used sham procedures and showed little or no symptom benefit, though critics said it was underpowered
- •Ethan tries medicines first and keeps stenting as an option if symptoms persist
- 1:29:33 – 1:40:30
Uncertainty, Evidence-Informed Medicine, and Preventive Cardiology
The conversation widens into the humility required in medicine, as facts change and trial averages do not map onto individual patients. Ethan describes the difficulty of prevention, where success is the absence of events and no trials exist, and Peter favors evidence-informed over evidence-based medicine.
- •All facts have a half-life, and being wrong can be a pleasure in science
- •Ethan struggles with how aggressive to be in preventive cardiology
- •Clinical trials give averages while clinicians must decide for individuals
- •Prevention trials would take decades and are unlikely to happen
- •Peter's book subtitle will be 'The Science and Art of Longevity'
- 1:40:30 – 1:51:08
Calcium Scores and What Zero Really Means
Ethan frames anatomic versus physiologic tests and explains the coronary artery calcium score as a way to decide how aggressive to be with medical therapy. They discuss how interpretation depends heavily on age, with young people having calcium and older people having none being the informative cases.
- •Anatomic tests like angiogram and CT differ from physiologic stress tests
- •Screening angiography is not considered appropriate; imaging tests mainly guide aggressiveness of statin and other therapy
- •A zero score is meaningless in the young but informative in the elderly
- •Peter argues that age acts as area-under-the-curve exposure, so Bayes' theorem makes zero informative only in older people
- •Very high scores and unusual family-history cases show the limits of lipid-based risk
- 1:51:08 – 2:01:07
CT Angiograms, Radiation, Cost, and HeartFlow
They discuss CT angiography, which shows plaque before it narrows the lumen, along with radiation dose, cost differences between institutions, and the risk of patient anxiety. They then discuss FFR and the FAME trials and why neither expects HeartFlow's CT-derived FFR to change management.
- •CTA reveals soft plaque that grows 'down before it grows up'
- •Modern scanners deliver about 2 millisieverts of radiation
- •Cost is a major barrier, with big price differences between institutions
- •Invasive FFR below 0.8 has been used to guide stenting
- •Neither doctor finds that HeartFlow's CT-FFR changes management, especially after ORBITA
- 2:01:07 – 2:15:27
Growth Hormone, the Sexually Dimorphic Liver, and Fatty Liver
Peter notes the whiteboard is full of mTOR and growth hormone pathways, and Ethan explains how his lab moved from clotting to sex differences to growth hormone. Pulsatile versus continuous GH secretion drives sex-specific liver gene expression, and knocking out Jak2 in hepatocytes produced massive fatty liver via CD36 uptake.
- •Ethan studied sex differences in clotting, which led to sexually dimorphic liver gene expression
- •Male and female growth hormone secretion patterns differ and drive that liver signature
- •Liver-specific Jak2 knockout caused a roughly 25-fold rise in liver fat
- •Circulating IGF-1 from the liver acts as a plasma biosensor for growth hormone
- •CD36 upregulation helped explain the fat uptake
- 2:15:27 – 2:23:31
Growth Hormone, Longevity, and Fasting
They discuss how excess GH shortens life while GH-receptor-deficient mice and Laron patients show protection from metabolic disease and cancer. Ethan answers about taking growth hormone, and the talk turns to IGF-1 and GH during fasting and ketogenic diets.
- •Acromegaly shortens life, and GHR-knockout mice are the longest-lived mice made
- •Laron patients in Ecuador had no cancer or diabetes in 30 years, but survival data are confounded
- •Ethan says every line of evidence suggests GH won't help longevity, but people may use it for how they look and feel
- •Peter would like to see a trial of raising IGF in early cognitive impairment
- •IGF-1 plummets during fasting while GH rises, suggesting selective hepatic GH resistance
- 2:23:31 – 2:38:31
Growth Hormone, Insulin Sensitivity, and Houssay's Legacy
Knocking out Jak2 in adipocytes made mice profoundly insulin sensitive, an effect traced to suppressed hepatic glucose production. Ethan describes Houssay's early work and the history of growth hormone's diabetogenic effects, and how GH and insulin co-evolved with GH acting as a brake on insulin signaling.
- •Adipocyte Jak2 knockout mice died of hypoglycemia on a normal insulin dose
- •Clamp studies showed the defect was in turning off endogenous glucose production
- •Houssay showed that removing the pituitary improved diabetes
- •Pegvisomant carries a hypoglycemia warning for diabetes drug users
- •Ethan sees GH acting as a brake on insulin signaling, converging on mTOR
- 2:38:31 – 2:54:10
Scientific Literacy and Keyto, the Breath Ketone Company
Peter asks how to make science exciting and Ethan discusses communication, early hyper-specialization, and giving medical students real lab experience. Ethan then describes Keyto, his breath acetone sensor company built around behavior change, and tells listeners where to find him.
- •Scientists must communicate with depth but in an engaging way
- •Early specialization makes it harder for non-science types to enter science and medicine
- •Ethan hopes to give MD-only students intensive lab experience
- •Keyto uses a breath acetone sensor and app to give feedback on ketosis
- •Ethan can be found on Twitter at @EthanJWeiss
