Thread by @NutritionMadeS3

Top takeaways from @Drlipid's new podcast with @PeterAttiaMD

00:07 recent evidence has emphasized:

1) atherogenic lipoproteins are the crux of ASCVD

2) effect of TGs on lipoprotein concentration/function

3) diminishing relevance of HDL-C

4) Lp(a)

peterattiamd.com/tomdayspring6/

00:32 brain cholesterol is separate from plasma; most cholesterol in the body is inside cells, not in bloodstream; most cholesterol in blood is in RBCs, not lipoproteins ▶️ so reducing serum cholesterol has little to no effect on cellular cholesterol requirements

00:36 it's not cholesterol in the arterial wall that poses a problem, it's trafficked cholesterol inside lipoproteins (digested by macrophages)

00:41 most people with low HDL-C have high ApoB. this may underlie the positive association btw HDL-C and CVD seen in observational studies

00:42 trials (via diff techniques and mechanisms) have consistently shown a neutral (at best) or detrimental (at worst) effect of raising HDL-C on CV risk

HDL particles may/probably play a role; HDL-C is a 'useless metric'

00:59 OxPL/ApoB measures oxidized phospholipids in apoB particles (predominantly on lp(a)) and may be an additional risk marker, particularly in those with high lp(a)

01:08 antisense oligonucleotides (ASO) in development for elevated lp(a)

01:09 statins can (in some people) raise lp(a), but net effect (via lowering of overall LDLs) is still likely positive

1:10 PCSK9is can lower lp(a) in addition to lowering LDL/LDL-c

TG content of lipoproteins (including LDLs) can determine particle half-life, structure and function

LDL-C is a reasonable yet imperfect metric of CV risk; nonHDL-C is a bit better; but ultimately risk tracks with ApoB (LDL-C and nonHDL-C can be misleading in discordant patients)

bempedoic acid (approved 2020) is a non-statin, cholesterol lowering drug that inhibits the cholesterol synthesis pathway (upstream of HMGCoA reductase, the target of statins)

01:35 bempedoic acid is hepato-selective and doesn't enter the myocyte, avoiding (or at least reducing) the muscle pain secondary effect of statins

01:40 TGs supported by both pharma and mendelian rando as important metric. can be lowered with fibrates or omega 3s (EPA/DHA, high doses required, >2g/d, max=4g, ≤1g likely does nothing)

fibrates can also lower apoB

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