Thread by @RichardAFerraro

So you've heard a lot of stuff, you've read a lot, maybe you listened to our podcast @cardionerds on it, and yet something is still missing.

TRIGLYCERIDES NEED A TWEETORIAL!

Let’s get right into it with 2 big points to start

#1: Lipids are insoluble in water. You’ve likely seen in this in science class or making salad dressing

What this means is that cholesterol and TG need to be transported with proteins in the body. So we add proteins + lipids and boom, we’ve got lipoproteins (LDL, ILD, VLDL, etc)

#2: The key to this TG story is Very Low-Density Lipoprotein (VLDL). VLDL is made by the liver of proteins, cholesterol, and TG

The ratio of TG to cholesterol depends on the size of the particle, with VLDL getting smaller as adipose and muscle pull TG out of circulating VLDL

Pull enough TG out and VLDL becomes INTERMEDIATE-Density Lipoprotein (IDL) which has ⬆️cholesterol than TG. Pull more TG and you get LOW-density lipoprotein (LDL).

Now we’ve all heard of LDL, it’s a big part of #ASCVD, treatment/guidelines. But IDL and VLDL cause #ASCVD too!

In fact prior work – including excellent meta-analysis by Boekholdt et. al. below – showed that the strength of association with future major cardiovascular events in statin-treated pts using non-HDL cholesterol (Which includes VLDL, etc.) was STRONGER than LDL cholesterol alone!

But I know what you’re thinking: Wait, don’t chylomicrons, large particles made by the GI and carry dietary fat, have TG too? Yes! And this is why eating a fatty meal before a lipid panel causes elevated TGs!

Now this part is cool: Do chylomicrons cause #ASCVD?

No! They’re too big!

#ASCVD is caused by lipoproteins crossing artery walls – the arterial intima – where they are scavenged by macrophages, and cause bad stuff leading to plaque.

VLDL can cross over, LDL can cross over, but chylomicrons are too big! Therefore, no plaque

So what do we do about this? Treat it!

One treatment of note is high-dose Omega 3 (I will speak to EPA specifically, DHA/EPA is a whole thing).

Omega-3s do many of things, like reducing inflammation and endothelial dysfunction, but a big one is⬇️VLDL production by the liver

In fact, a MARINE trial sub-study by Drs. Bays, @CBallantyneMD, and others of 229 participants with very high TG (>500) treated with Omega-3 backed this up, finding:
✅27.9% decrease in large VLDL
✅16.3% decrease in large LDL
✅25.6% decrease small LDL!

What about #ASCVD events? Well you’ve probably heard of the REDUCE-IT trial by @DLBHATT and colleagues

In 8179 pts already on statins, 4g of high-dose purified EPA/day led to:
✅25% reduction in the primary endpoint
✅>30% reduction in fatal or nonfatal MI!

Now its worth noting that the results in REDUCE-IT were independent of TG lowering, though sub-studies have shown the greatest benefit in those with high TG

But remember that EPA does much other than just TG⬇️, so that likely matters. Additional studies definitely needed here

Last point: Prescription EPA is💰. Can I just take over the counters? NO!

Despite 8% of US adults taking fish oil, MULTIPLE meta-analyses have shown no benefit from Omega-3 supplements

See more on this in @cardionerds podcast by the great Dr.@ErinMichos

cardionerds.com/161-lipids-tri…

CONCLUSIONS
✅TG is carried largely by VLDL
✅VLDL causes plaque, just like better-known LDL. So when you look at TG on a lipid panel, you’re really seeing VLDL (Also other things, but VLDL)
✅We can treat this with TG-lowering medications. These effect more than TG, but⬇️events

That’s a wrap!

Thanks to all @cardionerds friends and colleagues, especially @PatrickZakka & @AmitGoyalMD for reviewing this thread

Want to learn more? See our recent paper where you can find this and other highlights on contemporary lipid management

Grateful to Drs. Toth, @TLeucker @SethShayMartin @maciejbanach and Jones for their guidance on this piece!

link.springer.com/article/10.100…

References!
ncbi.nlm.nih.gov/books/NBK30589…
…ritionandmetabolism.biomedcentral.com/articles/10.11…
jamanetwork.com/journals/jama/…
tandfonline.com/doi/full/10.15…
lipidworld.biomedcentral.com/articles/10.11…
jacc.org/doi/full/10.10…
sciencedirect.com/science/articl…