1/4 Q#3 f/u: OK folks, this is the result of his genetic tests via @GBHealthWatch:
It shows he is heterozygous for a pathogenic ABCG5 mutation, c/w sitosterolemia. Not homozygous. No other FH/LDL mutations noted.
1/11 ACC 2022 Lp(a) Summary: @ACCinTouch 1- very high interest in Lp(a)- 2 live sessions and at least 10 abstracts. Lets see if @EASCongress in Milan in May can beat it! I will be there in person!
Summary of key findings follows:
2/11 2- The big news is we now have a 3rd drug reported to lower Lp(a)- SLN360- an siRNA that is very potent- up to 98% reduction with single dose. 2 caveats- at the highest dose, all pts had transient ⏫ CRP and ISRs, and we may not need/want to lower Lp(a) to zero
3/11 doi.org/10.1001/jama.2…
Risk of Lp(a) is flat at 0-30 mg/dL and up to 50 on statins, and at very low levels (< 5-10 mg/dL) there is an association with incident DM, but not clear if causal. Middle of strike zone is likely to get it to about 15-30 mg/dL but not <10.
It teases out the "laboratory LDL-C", compared to a more accurate LDL-C that is derived using our new laboratory technique to remove Lp(a)-C content in plasma.
2/4 It shows the corrected LDL-C is ~12-16 mg/dL lower than the lab value, and that most of the effect of pelacarsen is via lowering Lp(a). It also shows the gross inaccuracy of the 30% correction of Dahlen formula, which should now be retired to medical history.
3/4 Clinical implications: 1- in your pts w/ high Lp(a), the LDL-C is lower than you think, roughly proportional to how high Lp(a) is 2- to understand where residual risk CVD risk is coming from, need to know more accurate LDL-C and Lp(a)-C
This issue of statins and Lp(a) needs a new understanding. I treat virtually all my pts with statins, but we do need to understand what happens to Lp(a). This has been buried since 1989, mostly unintentionally- Brief summary below:
I believe one culprit was this lovastatin paper- Note the technically correct English, but incorrect message. Seems quite "lawyerly"- nobody can accuse you of lying, but yet again you did not tell the truth. "Lp(a) levels increased 33%"
The conclusion of the paper says it all- once one adjusts for apoB or TC/HDL ratio statistically, it provides no new information. So if you know apoB or TC/HDL ratio, it is not informative. The evidence is on the next few tweets, table 3 from Wu paper and Fig 1 from Holvoet paper
This shows if one adjust for apoB, p-value is now non-significant. Next tweets will explain why.
One needs to understand competition assays to interpret- If an antibody is used to bind its purported antigen, you can add a second unrelated "competitor" to see if it affects it. If binding is specific the comp should have no effect. B/B0- B presence comp, B0 in absence
5- Somatostatin analogues (growth hormone blockers for acromegaly)⬇️ Lp(a) 20-25%. GH is one of few hormones that raises Lp(a). I have wondered if the @NFL can use this to detect doping - A rapid increase with no obvious explanation would need further f/u pubmed.ncbi.nlm.nih.gov/34986497/
1/x For those interested, here are personal observations on 7 days of semi-Inuit diet. Not an expert, so take with broad context:
1- Why did I do it?: I have been reading about indigeneous cultures and diet, and wanted to see what it was like. Diet affects lipids, incl Lp(a)
2/x 2- What did I eat: grilled rare beef (in lieu of caribou and seal) and boiled salmon plus the soup- with a bit of salt and pepper, and a bit of olive oil in desperation. Washed down with water. I did have 2 espresso in AM and 1 tea in afternoon (got to live a bit 😀).
3/x 3- How did I feel? Took in about 1800 calories, along with 30-45 min jog/bike daily, not enough calories- felt mildly hungry all day, but not bad and tolerable. Otherwise mentally and physically same as usual- very good except minimally less energy