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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