Sam Tsimikas, MD
@Lpa_Doc
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Educational forum on Lp(a) and related areas. Professor UC San Diego.
San Diego, CA
Joined October 2016
For those interested in the Saturday Morning Lp(a) Class, the course is now linked to my bio and is open access. Big thanks to @TheBhupiThakur for organizing the twittorials. It is ~500 tweets in 24 classes. Syllabus enclosed. I wish to all the joy of learning.
All Sat morning classes by @Lpa_Doc is now linked to this updated thread. Enjoy.
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The study I cited did that, the baseline Lp(a) was ~200 nmol/L, and they were randomized to evolocumab vs placebo. Note % reduction is only 13.9%., so about 28 nmol/L or about 10-12 mg/dL in absolute terms. The non-specific agents do not match the potency of the specific drugs in
@Lpa_Doc The analysis's focus on normal Lp(a) levels is indeed a limitation when the clinical concern is often elevated Lp(a). The true challenge lies in understanding the interventions' effects on those patients. In your experience, what alternative study designs could better address.
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A major limitation these types of analyses is that they report changes in Lp(a) in mostly normal Lp(a) levels, and thus they are not reflecting clinical need, esp if shown as mean % change which can vary a lot. What we really need to know is what is the effect in people with.
☝️Effect of Lipid-lowering Therapies on Lp(a) Levels: A Comprehensive Meta-analysis of RCTs. ☝️New evidence just published in @ATHjournal !. 👉This comprehensive meta-analysis of 147 RCTs involving over 145,000 participants confirms that most currently available lipid-lowering
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And a little known fact: Dan was a UCSD Med School founder, in early 1960s- I happen to sit in hallowed ground in his original research office, BSB 1080. Joe is in same suite right across from me. A beautiful collaborative pairing of Cardiology and Endocrinology to study.
Yes! The giant of oxidation of lipoproteins, Dr Steinberg, passed away several year ago. Joe Witztum, who contributed initially significantly with Dan and then further refied the hypothesis with oxidation specific antibodies, and I still work together. The prior data was mostly.
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Yes! The giant of oxidation of lipoproteins, Dr Steinberg, passed away several year ago. Joe Witztum, who contributed initially significantly with Dan and then further refied the hypothesis with oxidation specific antibodies, and I still work together. The prior data was mostly.
@Lpa_Doc @UCSDCardiology I remember when you went to work in the Steinberg/Witzum lab. What a journey!.
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Thank you David. You were there at the very beginning when @UCSDCardiology.
@Lpa_Doc @FamilyHeartFdn Congratulations, Sam!.
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I am deeply honored to be invited to present the Pioneer Award lecture for the @FamilyHeartFdn. It will be a modern "bench-to-bedside" story through my collaborative work, experience and associations spanning 25 years to define Lp(a) as a CVD risk factor and develop a therapy for.
We’re proud to honor Dr. Sam Tsimikas @Lpa_Doc w/ the Pioneer Award at #FHFSummit25! After his Keynote lecture, join us for Lp(a) In the Spotlight w/ Diane MacDougall & Dr. Anne Tybjærg-Hansen sharing insights from new @FamilyHeartFdn Lp(a) research. #KnowLpa.
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Congrats Dhruv, well deserved, as a former @UCSDCardFellows you are a role model and we are proud of you!.
I’m usually awkward about award ceremonies – worthy accomplishments are seldom about individual effort. But this one warmed my heart. A celebration of folks who have dedicated decades of their lives to an organization that has truly shaped our the world. @American_Heart .1/
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A relatively new area for those interested in CV is Angiotensinogen as a new target for HTN and heart failure: See 2 papers on topic, led by Kari Lidani and Andrew DeFillipis. @ionispharma supported the measurement of AGT in the MESA study - its drug tonlamarsen is licensed to.
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RNA-based technologies are evolving extremely fast. If yearly dosing can be achieved for CV targets, treating risk factors will move to primary care with the annual physical. It will be a very exciting next decade to see how much further we can reduce CV events. .
Today, with @Biogen, we shared positive interim results from the Phase 1 study of our investigational ASO for the potential treatment of spinal muscular atrophy (#SMA). Read more: $IONS
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The larger olezarsen-apoC-III trials for severe hypertriglyceridemia read out this year in 2025. Pelacarsen Lp(a)HORIZON reads out in 2026. After an Odyssean, >10 yr journey, we are almost home. .
@Lpa_Doc @ionispharma When do outcomes come out.
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The world of triglycerides is rapidly evolving with potent therapies. See recent paper on FCS from the Balance open label extension study and patient reported outcomes.
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This is a nice confirmation, with a different technique (NMR), what we have known for 2 decades, that Lp(a) risk is independent of LDL-C and apoB. I think this other figure from the paper is more intuitive. One issue with NMR is it can't differentiate LDL/apoB from Lp(a), thus it
@Lpa_Doc this looks ace. 🤞🙏.
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RT @hsbhatia: Our new study on the AHA PREVENT Equations and Lp(a) is out now @JAMACardio @AlexRazavi @JSpitz_MD @jaideeppatelmd @DrMichael….
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RT @JAMACardio: The PREVENT equations effectively predict cardiovascular disease risk overall, including for individuals with elevated lipo….
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This is a good topic for Sat AM @OxPL_apoB Class. In fact, Lp-PLA2 inhibitors block OxPL from degrading, it was predicted to fail. Pelacarsen lowers OxPL-apoB 88%, and so does olpasiran. But a more direct way is in the works.
@JPSwcpmc Would have to get rid of Kringle IV-10. ? Is that possible? Not sure how to reduce oxPL-apoB concentration, Recall that phospholipase inhibitors failed in MACE trial, even though they significantly reduced Lp-Pla2. They are looking at what pelecarsen does to oxPL-apoB.
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Results of other poll, this one did not garner as much interest. This topic is not in clinical mainstream yet and it's in the "early adopter stage", but let's see in 2-3 years with more data. This is being rolled out as a research test in clinical trials if validated to impact
New poll: If you could order a directly measured Lp(a)-C and have the lipid panel be defined as TC = LDL-C(corrected), + Lp(a)-C + HDL-C + TG/5, and price was similar to LDL-C, would you use it to guide selection of therapy, and how often?:.
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Here are the results of this poll. Understanding what the true LDL-C is will become much more relevant as we have Lp(a) and maybe Tg lowering drugs for Tg 150-500 in future. Defining and treating the responsible lipoproteins will be important for individualized care. ApoB is a
Lets do one more poll to round things out for discussion: .You have a pt with CAD, family hx CAD (father MI 58) and lipid panel as follows: TC= 170, LDL-C by lab estimate or direct LDL-C = 75, TG = 225 (VLDL= 225/5 = 45), HDL-C = 50 on rosuva 40. What would you order next to.
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