AHA Lp(a) program:
1/4 2/4

1/13 Today, we have a special guest, @MWilkinsonMD presenting: "Saturday Morning Class #25- Lp(a) and plant based diet" Thank you Mike, and enjoy.. 2/13 1. Thanks @LPadoc for the invitation to discuss diet and Lp(a)!

1/9 @ACCinTouch 2023- Summary of key Lp(a) presentations.

On search function, there are 63 hits for “lipoprotein(a)”, and in ~1/3rd it was the primary focus.

1- 10 moderated posters
2- 3 oral presentations
3- 30 posters
4- 1 standing room only session
5- 19 “other” 2/9 Summary of presentations of interest:

1-Lp(a) HERITAGE, in US cohort, 25% had Lp(a)>70 mg/dL in overall cohort and 40% in Black participants, otherwise eligible for the trial @Novartis
2-Intermountain Health data (mostly white), 17% had Lp(a)>70 mg/dl, and had higher MACE

1/9 Summary of ESC 2022 highlights: @escardio
Lp(a) topics- 5 sessions, 2 industry sessions, ~25 abstracts:

1- Big news was @society_eas consensus statement (not guideline). Nice overview of the field in last 10 years. Bottom line, measure Lp(a) in all adults once. 2/9 Its similar to 2019 ESC/EAS guidelines, but did not qualify it to measure to pick up very high risk pts, so less likely to be criticized by payors
2- Risk of Lp(a) fairly continuous
3- Several other topics covered-very comprehensive.

With apoB getting more press, its time for some Twitter balance. My take is I rarely use it, as i need to know individual components, LDLC, Lp(a) and TG for Rx. So, here are 4 polls to set discussion: #1: I find measuring apoB changes my Rx decision x% of time #2 which drugs “directly” lower apoB as their primary mechanism?

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.

https://twitter.com/Lpa_Doc/status/1517015148866637824

2/4- Does being heterozygous for ABCG5 explain LDL-C >700?

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

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.

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%"

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.

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/

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 😀).

1/8 Observations on my ABIM exam for General Cardiology
1- for those not aware/grandfathered into Interventional Cardiology, if you stop doing procedures, like me, even if you pass the ABIM test, you will no longer be board certified. Keep in mind before you give up Gen Cards 2/8 2- it seems misguided for ABIM to kick someone out of the specialty because they willingly stop doing procedures, like that is all that matters (no brain needed)- we need to have @ACCinTouch and @SCAI provide another route to keep members active who wish to not do procedures

1/4 Time for the Answer: bottom line, all these can be associated with elevated Lp(a) as they are all young patients. However, the answer is the 48yo w/CAD and FHx. Why: the 55 yo can be explained by risk factors, although they would have to be severe, like FH; (next)...

https://twitter.com/Lpa_Doc/status/1441798956581732360

2/4 The 52 yo can be explained by presence of long-standing DM, especially if poorly controlled: the 48 yo with CAD and family history typifies life-long elevated Lp(a). The presence of family history implies a genetic risk factor like Lp(a); (next)...

1/4 A large study came out today in @JACCJournals on Lp(a) and long term outcomes in PCI:
jacc.org/doi/10.1016/j.…

@MitulPPatel1 and Ryan Reeves and I had the honor of writing the editorial:
jacc.org/doi/10.1016/j.… 2/4 Key findings:

1- Elevated Lp(a) present in 31% of pts undergoing PCI
2- Lp(a) not associated with classical restenosis within 1 yr
3- Lp(a) associated with worse long-term outcomes (death/MI/CVA)
4- Risk present in all major subgroups incl those with
LDL-C <70 mg/dL

Here is a f/u from Saturday Morning Class #10 Lp(a) and diet: Extra virgin Olive Oil (EVOO) and polyphenol content. Most EVOO have ~150-300 mg/kg polyphenols (pungent, burning taste) which are very potent anti-oxidants. This oil from liokareas.com has 1251 mg/kg Why so high?- polyphenol concentration is greatest when olives are less ripe and diminishes as olives ripen. So, to get high polyphenols one must pick them early, but at significantly less yield (so not typically done due to economic reasons)

1/21 Saturday Morning Class #23 Discovery of Lp(a) by Kare Berg

Hi all, back on twitter after a nice break to beasutiful Greece. Put this on your bucket list if you have not been there yet- you will not believe the natural beauty, sun, water, food and hospitality. 2/21 My goal for the last Class was to do a history of Lp(a), but on second thought this is likely a fool's errand for sound bites on twitter, as many people will be left out, so I will focus on the first paper on Lp(a) and review it in detail

1/21 After a long delay to submit NIH grants, we are ready for the next lesson: Saturday Morning Class #22: Lp(a) and racial/ethnic differences 2/21 First principles: Do racial ethnic differences exist in Lp(a) levels at a population level?. Answer- Yes
Does it make a difference what race/ethnicity you are at the individual level if Lp(a) is elevated?.....

1/11 Answer is D- laboratory error, but not the kind you are thinking of (robot pipette error leading to false value). Congrats to the 4.7% that answered D, hopefully it was for the right reason. This is a case of apparent "statin resistance" due to high Lp(a). Let me explain:

https://twitter.com/Lpa_Doc/status/1411359857437941761

2/11 Its not A as she was compliant as she filled all scripts by EPIC chart. In fairness this could not be known from question
Its not B, if she had malfunctioning LDLR and had minimal response to a statin, she would have to have homozygous FH, but these pts have LDL-C 300->1000

1/17 Saturday Morning Class #21 Lp(a) and kidney disease

First principles: Apo(a) of Lp(a) is synthesized almost exclusively by hepatocytes, then meets an LDL-sized particle either in or outside the cell, and by a poorly defined process creates a disulfide bond to make Lp(a) 2/17 Lp(a) then travels throughout the body, to do “its thing”. Unfortunately, “its thing" is unknown, i.e we don’t know why Lp(a) is only present in humans, apes monkey and the hedgehog, and not present in other mammals. Thus, its physiological function has been elusive so far.

1/6 Brief review of interesting recent Lp(a) literature:

1- In pts with baseline Lp(a) 120 mg/dL, PCSK9i reduced level to 93 mg/dL. Relative 22% reduction.
onlinelibrary.wiley.com/doi/epdf/10.10… 2/2 2- In pts with type 2 DM and high TGs, PCSK9i lowered Lp(a) ~42-49%, but they had low baseline Lp(a), so not clear if same would be seen in high Lp(a). Issue of Lp(a) in high TG needs more study. pubmed.ncbi.nlm.nih.gov/33941192/