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.

Today, $IONS will host an investor webcast to discuss the Phase 3 topline results for our treatment for severe hypertriglyceridemia (sHTG).  Access a link to the webcast here: https://t.co/9rFxYUkMyl

The landmark Phase 3 CORE and CORE2 data are very exciting for people living with sHTG and the physicians who care for them. People with sHTG live with triglyceride levels more than three times higher than normal. Even with standard of care lipid-lowering therapies, diet and

Some great slides from #Guidelines discussion on triglycerides reduction. Check them out. 📉 Not all TG-lowering therapies equal CV benefit. •Statins: ↓TG 15–26% ✅ CV benefit •Fibrates: ↓TG ~26% ❌ no clear CV benefit •High-dose icosapent ethyl (EPA): ↓TG 20% ✅ CV

These figures from NEJM tell the story-and 85-88% of subjects achieved a normal triglyceride level of <150 mg/dL, on top of standard of standard of care incl. statins, fibrates and omega-3 fatty acids. A big thank you to site PIs, coordinators, TIMI Study Group and @ionispharma

Big event at ESC this Saturday on the ESSENCE TIMI 73b trial for those interested in triglycerides and implications. The world of TGs for broader populations than FCS is being re-imagined with new potential therapies. @BrianBergmark @BNordestgaard

Note the average estimated age in these studies was 43 years old. The prevalence of calcified arteries seems similar to modern society males. I am not arguing LDL is not causal, but that the LDL-C was likely higher than we think, that clinical (not to mention subclinical)

Its nearly impossible to study hunter gatherers in modern times to make conclusions they have no atherosclerosis. Its difficult to gather robust data and many die of other etiologies. The evidence from CT scans of calcified arteries form mummies from multiple ancient peoples,

I think it an oversimplification to say most animals but humans have such low LDL-C. This does not apply to our closest relatives, great apes. For example, chimps in the wild on a mostly vegetarian diet have LDL-C ~80-120 mg/dL, and in captivity can be even higher in 170s. Their

A new paper is out @LipidJournal validating the NAFCS score for patients with FCS (Familial chylomicronemia Syndrome- i.e milky plasma) using the Balance genetic data. It will be an alternative method to make the diagnosis of FCS clinically. @ionispharma https://t.co/d2yCRZXan9

Great question, and that is the reason everyone thought that would be the case. However, when things don't go as expected, it leads to new knowledge. In this case, the apo(a) component creates a blocking hindrance so the LDL receptor has difficulty recognizing and taking up Lp(a)

Besides smoking and blood pressure: Lp(a), remnant cholesterol, obesity, diabetes, inactivity, stress, unhealthy diet, unknown genetics, and in some cases, we control all we can and we still see progression.

That would be nice. Unfortunately, biology is messy and not binary and there are many levels and layers of evidence to assimilate. And in some cases, 2 things may be true- like in this case- some lipid rich plaques calcify, yet new ones become lipid rich- so both can be true- not

I hate to be the contrarian, and that may be true, but not necessarily. Often, there is progression of both calcified and non-calcified plaque, and a CAC scan will not tell you this, one needs a CT angio. This occurs when LDL-C is not low enough or non-LDL-C factors drive

Except our paper, all meta-analyses used study level data, different assays, different labs, timepoints, etc. Unless one has access to individual patient data and rigorous methodology, meta-analyses at trial levels can be misleading, esp when Lp(a) values can be (0.3-300 nmol/L)

We’re proud to share that our medicine for familial chylomicronemia syndrome (FCS) has been nominated for the #PrixGalien USA Award for Best Product for Rare/Orphan Diseases! Thank you @GalienFdn! https://t.co/QpSzVu4SvY #PrixGalien #LivingwithFCS #RareDisease

Results of the poll with 140 votes-60% of respondents noted increase in Lp(a) post statin. Results are concordant with our meta-analysis of 5280 pts, 61.2% had an increase post statin. Bottom line: large variability is present (incl in placebo), many pts have clinically

LDL-C and Lp(a) are "risk factors" for CVD, not a disease per se. Thus, a higher proportion of people with elevated levels will get the disease, but not 100%. Lifetime risk depends on levels. Like smoking and lung cancer. The number of factors that influence clinical expression

It's actually a very relevant question- larger picture, what is the physiological role of Lp(a)? It does not appear to be an LDL-like function however. The ongoing studies should clarify if any untoward events will be seen with extreme Lp(a) lowering. I tried to address some this

A new poll of interest for patients and physicians/providers: In your personal experience with PCSK9i and Lp(a) lowering in people with Lp(a) >50 mg/dL (>100-125 nmol/L), what is the typical response you have observed:

One interesting issues with PCSK9i and Lp(a) reduction is they work best in people with low/modest Lp(a) elevation but less well or not at all in some people with elevated Lp(a). % changes can also be deceiving (i.e. large % change can be seen when levels are low but are not