Cardiovascular disease & why we should change the way we assess risk | The Peter Attia Drive Podcast
- Guest
- Allan Sniderman
- Read time
- ~5 min
- Uploaded
- 29 Nov 2021
- Duration
- 2:25:35
- Views
- 307.3K
KEYPOINTS
- 01
The 10-year risk window hides most premature heart disease
Nearly every major guideline decides who gets a statin for prevention based on 10-year risk. Sniderman calls that a big step forward in 1980–1990 that has since become a trap. Age dominates the calculators, so almost everyone under about 55–60 scores 'low', even while atherosclerosis is building through their 30s, 40s and 50s. By the time the 10-year number looks alarming, decades of disease are already in place.
- 02
A risk percentage is a statement about a group, not a person
A 4.1% 10-year risk means about 4 of every 100 similar people will have an event. It doesn't say whether you will. Different algorithms can give the same person 10%, 15% or 20%. Treating at a 7.5% threshold also means 92.5% of those treated would have had no event in that decade, which Sniderman says is a weak motivator.
- 03
Particles drive atherosclerosis more than the cholesterol they carry
Each atherogenic lipoprotein (LDL, VLDL, remnants, Lp(a)) carries one apoB molecule, so apoB counts the particles that can enter the artery wall. Total and LDL cholesterol measure cargo. Sniderman has argued since his first clinical paper around 1980 that particle number beats cholesterol concentration, and says the evidence for that is now very strong.
- 04
Standard lipid panels estimate rather than measure
The LDL number on a routine panel is almost always calculated, not measured directly. Sniderman notes that the apoB assay was standardized in 1994, while HDL cholesterol measurement is not standardized. He sees no technical reason apoB can't be routine.
- 05
Triglycerides flag risk, but the cholesterol in VLDL particles is what does harm
Sniderman says very high triglycerides raise the risk of pancreatitis, but he hasn't seen solid evidence that triglyceride itself causes atherosclerosis. What causes it is the cholesterol inside VLDL particles and how many of them get into the artery wall.
- 06
Remnant type III dyslipoproteinemia is missed without apoB
This highly atherogenic disorder shows high triglycerides and high cholesterol but a low or normal apoB, because the particles that pile up are cholesterol-rich VLDL remnants. Without an apoB measurement, and with old diagnostic methods abandoned, most cases in the US go unrecognized. Statins and/or fibrates usually work very well.
- 07
Mendelian randomization has been a 'slam dunk' for apoB
Long observational studies are confounded because people change over 20–30 years. Mendelian randomization uses genetic variants assigned at conception as a natural randomized trial, often in hundreds of thousands of people. Sniderman says these studies point to apoB as the causal driver.
- 08
Lipid status at 35 is surprisingly stable
Sniderman says groups can be classified fairly accurately at 35. Someone high at that age has about a 95% chance of staying high, and the ~5% who move don't become low. That's why he favors acting early in people who are clearly high, while noting that menopause and other changes still need follow-up.
- 09
Early treatment should be targeted, not universal
A 2019 Circulation paper by his group modeled delaying treatment from 35 to 45 to 55. With a low non-HDL cholesterol, starting at 35 gains little. The big gains go to people with high non-HDL or apoB, roughly 20% of the population by his estimate. So pills for everyone at 35 is not the conclusion.
- 10
Consensus culture is science's crucial weakness
Sniderman compares guideline committees to groupthink behind bad decisions such as Afghanistan and the 2008 financial crisis: 'when everybody in the room has the same opinion going in,' problems get solved badly. He says medicine has become less critical, and that 'dumbing down' recommendations for doctors who see 40 patients a day is a compromise on truth. He is pessimistic that apoB will replace LDL in US training within 10 years, despite Europe's pro-apoB 2019 guidelines.
- 11
Think in 30-year and lifetime risk, like retirement savings
A retirement calculator that only looked 10 years ahead would be useless to a 30-year-old. Peter and Sniderman argue the same applies to arteries. A 50-year-old should care about being 80, not 60. A cut from 4% to 2% over a decade looks trivial, but it compounds by 70.
EXAMPLES
- 01
Ancel Keys and the 200 mg/dL split
In the late 1950s, early total-cholesterol assays showed a clear difference in cardiovascular risk between people above and below roughly 200 mg/dL. That launched the cholesterol-centered model. Fredrickson, Levy and Lees later worked on lipoprotein classification in the 1970s.
- 02
The FOURIER debate
Peter recounts an email argument about FOURIER (the PCSK9 inhibitor Repatha). People already on high-dose statins with an average LDL-C around 70 mg/dL had fewer revascularizations over roughly five years, but no change in mortality. Sniderman's view is that it's almost a miracle the trial showed anything, since patients started so low and were followed so briefly.
- 03
A familial hypercholesterolemia result he thinks is wrong
A study reported that people with a genetic FH mutation had three to five times the risk of people with the same lipid levels but no mutation. Sniderman read it repeatedly and concluded the authors had made a methodological error, while admitting he may be wrong. His point is that FH is defined by the phenotype.
- 04
Risk factors explain little of individual risk
Citing Michael Pencina's work (the name is uncertain in the recording), Sniderman says standard variables explain only about 20% of the variance in risk. He argues that grouping people by causal, precisely measured markers like apoB or non-HDL selects patients more accurately than noisy multi-factor calculators.
- 05
The $10 test argument
His group's cost analysis put an apoB test at about $10, a negligible share of care costs. US health spending was about $7,000 per person per year a decade earlier and is now near $10,000. Cost, he says, is not a real barrier.
OTHER RELEVANT
- 01
Ask for apoB and Lp(a), not just a standard panel
Sniderman measures a lipid panel, apoB and Lp(a) in every patient (Lp(a) once). High Lp(a) with normal apoB may add little, but both high is a 'double whammy' that changes how he frames risk.
- 02
Use apoB to show patients progress
Seeing apoB fall from 120 to 60 tells both doctor and patient that the medication is being taken and working. That makes it a motivational tool, not just a diagnostic one.
- 03
Interpret calcium scores by age
A CAC of zero doesn't rule out risk in someone with very high apoB. But any calcium under age 50 is significant, even if the 10-year model calls it about 4%. Peter's view is that prevention aims to stop lesions forming, which is '100% success', rather than treating them late.
- 04
Embrace uncertainty instead of false precision
Sniderman wants doctors to say what they believe and why, admit that confidence intervals can be wide, and welcome open challenges, such as being confronted with a specific line of your own paper. Science that says the same thing as 30 years ago may not have learned anything.