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Sam Tsimikas, MD

@Lpa_Doc

Apr 7

@ACCinTouch

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.

Read 11 tweets

Sam Tsimikas, MD

@Lpa_Doc

Mar 14

@JACCJournals

1/4 Hot off the @JACCJournals press is our latest pelacarsen paper, @ionispharma @Novartis.

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.

sciencedirect.com/science/articl…

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

Read 4 tweets

Sam Tsimikas, MD

@Lpa_Doc

Jan 20

https://twitter.com/Lpa_Doc/status/1483981389531779072

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:

https://twitter.com/Lpa_Doc/status/1483981389531779072

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%"

See table for this paper on Lp(a) post lovastatin

Read 8 tweets

Sam Tsimikas, MD

@Lpa_Doc

Jan 12

https://twitter.com/The_Nutrivore/status/1481287099643207680

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

https://twitter.com/The_Nutrivore/status/1481287099643207680

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

Read 6 tweets

Sam Tsimikas, MD

@Lpa_Doc

Jan 10

@OxPL_apoB

Latest Lp(a) news:

1- pts w/ anti-phospholipid syndrome have ⏫ Lp(a) (116 vs 36 mg/dl, p=0.0002). pubmed.ncbi.nlm.nih.gov/35000119/

Note a portion of these ABs are to @OxPL_apoB - shown by J Witztum ncbi.nlm.nih.gov/pubmed/9294215

Likely OxPL-apoB will be extremely high in these pts

2- Lp(a) associated with chronic kidney dz in mendelian rand study- pubmed.ncbi.nlm.nih.gov/34999880/

3- Lp(a)/COVID paper now available- pubmed.ncbi.nlm.nih.gov/34995986/

4- Pts with ⏫ Lp(a) seem to benefit from prolonged dual anti-platelet therapy post PCI pubmed.ncbi.nlm.nih.gov/34988134/

@NFL

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/

Read 5 tweets

Sam Tsimikas, MD

@Lpa_Doc

Jan 8

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

Read 14 tweets

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