Peter Attia MD247 ‒ Preventing cardiovascular disease: the latest in imaging, blood pressure & metabolic health
CHAPTERS
- 0:02 – 7:15
Ethan's career shift and a recap of the calcium score
Peter Attia welcomes Ethan Weiss back and asks about his move from running a lab at UCSF to helping build a new biotech company. They then recap what a calcium score is, what it shows, how cheap and low-risk it is, and when it is and isn't informative.
- •Ethan closed his lab, became volunteer clinical faculty at UCSF, and now works on building a biotech company
- •A calcium scan shows the site of prior injury and correlates with the amount of plaque and the risk of adverse outcomes
- •Calcium scans involve very low radiation and no dye, but prices range from about $200 to $2,000 for the same scan
- •Ethan did a full 180 from finding calcium scans annoying to using them regularly
- •Scans are least informative in a young person with a zero score or an elderly person with many risk factors and a zero score
- 7:15 – 12:06
Peter's own CAC and CTA results and the imprecision of calcium scoring
Peter describes his calcium scores of six, zero and two over about 15 years, and a CTA that showed the same tiny lesion each time. He explains that thick-slice calcium scans can miss small lesions and cites data that about 15% of people with a zero CAC have a finding on CTA.
- •Peter's score was six in 2008-09, zero in 2016 and two in 2022, while the CTA showed the same tiny lesion
- •Calcium scan slices are thicker than CTA slices, so small specks can be missed
- •About 15% of people with a zero CAC have a finding on CTA, and roughly 1.5-2% have an unstable plaque
- •Ethan asks whether that 15% is concentrated in younger people, and Peter says he will look up the study
- 12:06 – 19:39
ApoB lowering and whether apoB is necessary or sufficient
Ethan asks about Peter's apoB over the years, and Peter explains his 30-40 mg/dL target despite never having had high apoB. They discuss whether apoB is necessary and/or sufficient for atherosclerosis, using FH, smoking and lung cancer as analogies and dismissing arguments that high apoB is harmless.
- •Peter targets an apoB of 30-40 mg/dL using pharmacology; his apoB was around 85-90 in his mid-30s
- •Peter argues apoB is necessary but not sufficient, so removing it removes atherosclerosis
- •Ethan agrees on necessity but thinks apoB may be sufficient in cases like FH, though some FH patients never develop ASCVD
- •The smoking and lung cancer analogy: a risk factor that is neither necessary nor sufficient still warrants reduction
- •Peter notes apoB can be treated pharmacologically regardless of diet
- 19:39 – 30:57
CTA versus calcium scan: cost, radiation and what plaque tells us
The two compare CTA with calcium scanning, covering extra information, contrast and radiation, and out-of-pocket costs that vary widely. They then discuss soft versus calcified plaque, and Ethan explains why he treats any plaque as a problem since we cannot yet reliably predict vulnerability.
- •CTA gives more information at the cost of some radiation, contrast risk and a harder time getting it paid for
- •CTAs cost from about $700 to $3,000, and Peter notes radiation can vary tenfold between scanners (about 2 vs 20 mSv)
- •Soft plaque doesn't show on a calcium score, so significant disease can exist with a zero CAC
- •Ethan doesn't think plaque characteristics can yet change management; he treats any plaque, including 30% plaque, maximally
- •Plaques that cause events are often not the most stenotic ones
- 30:57 – 34:12
Treating early and the lack of gold-standard prevention trials
Peter and Ethan argue that waiting for a stenosis or high calcium score before acting is backward, using the smoking analogy and insurance demands for an event before PCSK9 inhibitors. They agree that the key long-horizon trials in 40-year-olds will never be done, and Peter says ASCVD could become an orphan disease.
- •Treat causal risk factors early rather than waiting for end-stage findings
- •Insurers sometimes require an event before approving PCSK9 inhibitors, which Ethan finds absurd
- •Trials are too expensive to answer the most important questions, such as 30-year outcomes in 40-year-olds
- •Peter says ASCVD should be an orphan disease if started early and treated aggressively
- 34:12 – 48:56
FFR and when stenting is indicated
Ethan explains how FFR works and the FAME trials, then lays out when stenting is clearly indicated (STEMI, ACS, unstable symptoms) versus when optimal medical therapy is preferred. He cites trials such as COURAGE, and Peter asks about symptomatic and asymptomatic patients with high calcium.
- •FFR measures the pressure gradient across a stenosis, like squeezing a garden hose
- •STEMI calls for immediate primary PCI, and ACS usually leads to early stenting within about 24 hours
- •Patients with plaque but no symptoms are generally treated medically, per COURAGE and later trials
- •For stable angina, Ethan favors a trial of optimal medical therapy before stenting
- •Ethan doesn't routinely stress test patients with high calcium scores or use stress tests to follow coronary disease
- 48:56 – 1:01:31
Why medical therapy over stenting, and the limits of CT-FFR
Ethan questions whether any asymptomatic group benefits from stenting, and speculates on why opening a blocked artery may not help. They discuss the unpublished PRECISE results showing reduced catheterization but no change in MACE, and why neither physician sees a use case for CT-FFR.
- •No group outside acute MI has clearly been shown to benefit from stenting beyond optimal medical therapy
- •Possible explanations include collateral growth, plaque contents released downstream, and troponin rise after PCI
- •The PRECISE abstract showed no difference in mortality or MACE, only fewer catheterizations
- •Ethan says the same stents could be avoided without FFR by simply not sending asymptomatic patients to the cath lab
- •Ethan pulls all the levers whenever plaque is present, and mentions Verve's CRISPR approach to PCSK9
- 1:01:31 – 1:04:00
Fat attenuation index and measuring plaque inflammation
Peter asks about the fat attenuation index, a CTA add-on meant to gauge inflammation around plaque. Ethan admits he is unfamiliar with it, mentions FDG-PET for plaque inflammation, and notes that he is already pulling all the levers regardless.
- •FAI is described by Peter as a CTA bolt-on looking at fat around the plaque to estimate inflammation
- •Ethan is not familiar with FAI and says he tunes out new CT add-ons
- •FDG PET can quantify plaque inflammation and has been used in drug development, but not routinely in clinical care
- •Ethan says the information might shift focus toward metabolic issues
- 1:04:00 – 1:10:54
Exercise, statins and coronary calcification
Peter raises the claim that very fit athletes may have more coronary calcification. Ethan finds it plausible but says it is not a reason to dismiss calcium, unlike with statins, where calcification can rise even as risk falls. He recommends treating the calcium as plaque and suggests a CTA if needed.
- •Increased shear force during extreme exercise could plausibly cause damage and calcification
- •Statins are the one clear case where calcification can rise while events fall
- •Peter points out that more exercise is better and more calcium is worse, with no exception seen
- •Ethan won't give athletes a pass on their calcium and would use CTA to check for actual plaque
- 1:10:54 – 1:17:08
Statin hesitancy and its roots
Ethan estimates 90-95% of his patients take statins, with a small group intolerant and an equal or larger group afraid of them. They discuss the campaign against statins, general skepticism of big pharma, and holding contradictory truths about pharma at once.
- •A small number of Ethan's patients have true side effects, and a slightly larger group refuses out of fear
- •Ethan attributes the fear to a decades-long campaign demonizing statins and to documentaries
- •He says it is easier to scare people than to un-scare them and compares it to MMR vaccine fears
- •Peter says people struggle to hold contradictory truths, such as pharma companies doing both good and bad
- •Ethan never forces a statin and sometimes spends years on the conversation
- 1:17:08 – 1:28:47
Why blood pressure matters and what counts as normal
Peter explains his interest in blood pressure through the kidney and asks how it ranks among ASCVD risk factors. Ethan discusses the kidney's role in blood pressure, whether rising pressure with age is normal, and concludes that 120/80 is the target at any age, as close as possible without harm.
- •Peter says even slight blood pressure elevation affects kidney, heart and brain health
- •Ethan describes single-gene mutations affecting blood pressure that cluster in the kidney tubule
- •Blood pressure rises with age epidemiologically, but Ethan no longer considers that a normal part of aging
- •Ethan's goal is to get patients as close to 120/80 as possible without harming them
- 1:28:47 – 1:45:05
Blood pressure variability, measurement and the SPRINT protocol
They discuss how much blood pressure varies through the day, how SPRINT measured it, and Peter's experience of home readings. Ethan suggests 24-hour ambulatory monitoring, and they note the lack of good continuous devices and the gaps in awareness, treatment and control.
- •Blood pressure varies greatly from moment to moment, and Ethan relies on how the trials measured it
- •SPRINT used an automated cuff, with the patient seated alone and the average of three readings taken five minutes apart
- •Peter's first reading on sitting can be 140/90 and falls to normal after five calm minutes
- •Ethan recommends 24-hour ambulatory monitoring and says no wearable device yet measures BP accurately
- •Awareness, treatment and control have improved since 1975, but control may still be only about 50%
- 1:45:05 – 1:54:04
ALLHAT, SPRINT and STEP: trial evidence on treating hypertension
Ethan reviews ALLHAT, which found that ACE inhibitors, amlodipine and thiazide-type diuretics were all acceptable first-line drugs. He then covers why SPRINT was run, its early stop for benefit and its risks, and how STEP confirmed the result in a broader population including people with diabetes.
- •ALLHAT stopped the alpha and beta blocker arms for harm and found no real difference among the other three classes
- •SPRINT, NIH-sponsored and drug-agnostic, randomized to about 121 versus 136 systolic and stopped early for benefit
- •Risks included falls, syncope and reversible kidney dysfunction, and Peter shared his own fall from low blood pressure
- •Ethan notes that blood pressure has a U-shaped curve, unlike apoB
- •STEP confirmed SPRINT and included patients with type 2 diabetes
- 1:54:04 – 2:03:06
Choosing antihypertensive drugs and tolerability
Peter asks whether any drug class should be preferred when blood pressure is equally lowered. Ethan says first priority is simply getting to goal, then describes how he picks among chlorthalidone, amlodipine, and ACE inhibitors or ARBs based on age, comorbidities and side effects.
- •Ethan's first advice is to get blood pressure controlled before optimizing the agent
- •He considers chlorthalidone or a thiazide the best all-round agent but harder to use, while amlodipine is easiest, though ankle swelling can bother people
- •ACE inhibitors or ARBs are favored for ASCVD, existing kidney disease, diabetes and enlarged aortic size, and need electrolyte monitoring
- •He avoids diuretics in older people because of electrolytes and fall risk
- •Tolerability is a major driver of non-compliance
- 2:03:06 – 2:24:54
Metabolic health, fat storage capacity and lipodystrophy
Peter lists metabolic health as a fourth pillar of ASCVD risk and uses a bathtub analogy for fat storage capacity. Ethan explains that where fat is stored matters, describes lipodystrophy as an extreme example, and says his new company aims to find targeted therapies based on genetics and the fat mass ratio.
- •Peter's four pillars are smoking, hypertension, apoB and metabolic health, using the bathtub analogy for storage capacity
- •Ethan says where fat is carried matters more than how much, with gluteofemoral storage protective
- •People with lipodystrophy and severe insulin resistance have extreme coronary disease risk, sometimes needing bypass in their 30s and 40s
- •The ratio of upper-body to leg fat (fat mass ratio) has genetic determinants and is a strong predictor of risk
- •Ethan says lipodystrophy is badly under-diagnosed and expects targeted therapies tested first in lipodystrophy
- •He says upcoming papers will show FMR conveys more risk than smoking status
