Peter on how early and aggressive lowering of apoB could change the course of ASCVD

This audio clip is from episode #202 – Peter on nutrition, disease prevention, sleep, and more, originally released on April 11, 2022.

Show Notes

Cardiovascular disease: how early and aggressive lowering of apoB could change the course of ASCVD [31:30]

How Peter has changed on ASCVD: He’s become far more aggressive on the timing and magnitude of ApoB reduction

What are the leading causes or modifiable causes of ASCVD? 

• Big three:
• i) smoking, 
• ii) hypertension, and 
• iii) hyperbetalipoproteinemia
  • Fancy word for saying too many lipoproteins that have ApoB on them (LDL, IDL, VLDL, Lp(a))

Measuring ApoB

• Peter is such a fan of measuring ApoB as opposed to just measuring LP, LDL, particle number, or LDL cholesterol number because we have one single number that captures the total concentration of ApoB
• While that’s pretty well associated with non HDL cholesterol—which is a far better surrogate than LDL cholesterol—it’s still better and that’s been demonstrated 
  • A previous podcast covered the discordance between non HDL cholesterol and ApoB

The question becomes: “When should you start ApoB reduction and how much should you lower it?”

• Some numbers: The 20th percentile of ApoB is about 80 milligrams per deciliter
• Let’s say somebody was at the 50th percentile, they’re 40 years old, their calcium score is zero, and they were ambivalent about lipid lowering therapy and let’s assume that they’re not insulin resistant and you’ve done all of the things that you can do reasonably with nutrition
• In the recent past, Peter wouldn’t push that hard to take action
• Today, he takes a very different stance which is treat early and treat aggressively 

Bold statement incoming: If you pharmacologically lower ApoB to somewhere in the 20 to 30 milligram per deciliter range for everybody in the population while someone is in their 20s, can you eliminate ASCVD?  ⇒ I think the answer is probably yes

• In other words, what you’re basically going to do is eliminate death from atherosclerotic causes
• How do you take that thought experiment and turn it into a practical implication?
• Well, it’s not really practical to take every 20 year old and obliterate their ApoB (although this could and should be done with patients with significant genetic abnormalities that result in familial hypercholesterolemia)
• Practically what it means is basically by the time you’re in your late 30s or early 40s, if you have any measure of ApoB that’s even north of the 20th percentile, that should be completely lowered
• Peter views the “ceiling” to be ~60 milligrams per deciliter
• Peter wants everybody to be below the 5th percentile

*Additional resources: 

• Check out AMA #34 for a deep dive into ASCVD 
• Episode #185 with Allan Sniderman 

Rough percentile numbers:

• 5th percentile = 62 (from the Framingham Offspring Study)
• 10th percentile is about 70 
• 20th percentile is about 78
• 50th percentile is about 97
• 80th percentile is 118
• 95th percentile is about 140

“I just don’t see a reason to have an ApoB ever north of 60 milligrams per deciliter.” —Peter Attia

How to lower ApoB:

• When you look at a lot of the Mendelian randomizations plus the clinical trial data, if you have an LDL cholesterol below 30 or an ApoB below 40 milligrams per deciliter for a very long period of time, I think the odds that you’re going to suffer for ASCVD are incredibly low
• The earlier you start and the lower you go the more you can make that number approximate zero

And therefore it then only becomes a question of: What are your therapeutic choices to get there? And how do you do this in a way that minimizes the side effects of that?

• Because for some people to lower ApoB that much is trivial — Peter takes a PCSK9 inhibitor and a statin and he can basically eradicate it 
• But for some people, statins are difficult to tolerate
  • About 5% of the population has intractable muscle soreness and that appears to be the case regardless of which statin you use and we tend to rotate through different statins
• Peter likes to start patients with rosuvastatin or pravastatin
• If they have difficulties there, move to pitavastatin (Livalo)
• But if people can’t tolerate any of those things, today we have so many other options
  • If they’re a hyper absorber we would use ezetimibe
  • if they’re a hyper synthesizer, but can’t respond to statins, we use mefenamic acid
• “We have lots of tools up our sleeve today more than ever before and that’s why I just think we should be more and more aggressive on this now.”