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Sam Tsimikas, MD

@Lpa_Doc

21 Mar

@stsimikas

1/4 Costs of PCSK9 antibodies (initially $14k/yr, now ~$5-6/yr) will come up, so here is a brief summary of this.

1- antibodies are very expensive to make as they are large proteins and have to be made in a biological system rather than chemical synthesis
@stsimikas @OxPL_apoB

2/4 2- I dont know what they break even point is, but I suspect you cant make them for <$2-3K/yr, so price will not likely come down more as there will be little profit.
3- at 150 mg every 2 weeks, this is 3,900 mg/yr per patient, so cost is ~$1.50 per mg

3/4 4- for context, in our research lab, 0.1 mg of most research antibodies, that don't need human testing, is ~$300, or ~$3000/mg, i.e about 1500 times more expensive that Repatha and Praluent. If we had to buy 3,900 mg per year, it would cost us over $100,000K

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Sam Tsimikas, MD

@Lpa_Doc

21 Mar

1/20 Saturday Morning Class #16 Lp(a) and PCSK9i

Apologies for delay. We had a tragedy this week- our 2 kids' dear cats Captain Jack and Leonardo, who have graced these pages, were taken by a bobcat and her 3 kittens. Good bye dear friends, we will miss you and never forget you

2/20 First some definitions- what is a PCSK9 protein (Proprotein convertase subtilisin/kexin type 9 (PCSK9). As the name implies, it cleaves other proteins to convert them to an active form. The one of interest to lipid metabolism is type 9.

3/20 It is secreted by the liver, and binds to lipoproteins (LDL, HDL and Lp(a)) in plasma. It then comes back to the liver on LDL/Lp(a) that bind to the LDL receptor. The LDLR/PCSK9 gets internalized and the LDLR is destroyed, resulting in less LDLR in liver cell surface

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Sam Tsimikas, MD

@Lpa_Doc

17 Mar

https://twitter.com/UKLowCarb/status/1372110949562384388

1/4 Not something I want to dwell on but I had a disclaimer in the tweet that said it depends on how meat is processed. For the study I was referring to, they did measure carbs in meat and there was daily ingestion of liver which will have lots of glycogen, as well as cholesterol

https://twitter.com/UKLowCarb/status/1372110949562384388

2/4 If the animals are slaughtered in the fasting state, then most glycogen will be depleted or used up to make lactic acid in rigor mortis (ATP depletetion) assuming they dont process it quickly. In modern day, I suspect glycogen (carb) content of muscle (i.e steak) is only 1-2%

3/4 For my own practice, I highly discourage "animal product" keto diets in my patients, simply because they already either have CVD or high risk for it, or genetic disorders that raise their LDL-C, and eating saturated fat and cholesterol is the worst thing they can do

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Sam Tsimikas, MD

@Lpa_Doc

15 Mar

@stsimikas

1/12x This is a follow-up to Saturday Morning Class #10 Lp(a) and diet. @stsimikas @OxPL_apoB It shows there is nothing new under the sun. It’s an interesting story of Vilhjalmur Stefansson Arctic explorer from early 1900’s.

2/12 He lived among the Inuits (AKA Eskimos), who then ate a carnivore diet (sea mammals, fish, wild game, no carbs or vegetables) and only drank water. This is the same diet our 2 cats, Captain Jack and Leonardo, eat.

3/12 He ate this diet and only drank water and had no untoward effects, except when eating very lean meat with no fat in winter from wild game that had no fat, developing diarrhea and other symptoms (back then it was called “protein poisoning”).

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Sam Tsimikas, MD

@Lpa_Doc

6 Mar

@stsimikas

1/7 This issue come up a lot, here is my take on this: @stsimikas @OxPL_apoB

1- ApoB-100 represents all cholesterol-rich particles (VLDL, IDL, LDL, Lp(a)) and laboratory calculated or measured "LDL-C" is really IDL, LDL, Lp(a). So when you order an apoB you also get VLDL-apoB

https://twitter.com/ethanjweiss/status/1368201696803921924

2/7 2- if the patient has normal TG, VLDL-C (and remnant cholesterol) is very low, so in this case apoB adds very little. In fact, correlation of apoB with LDL is >0.9, so not worth the extra expense

3/7 3- If TG/VLDL is elevated, the chol content shifts to larger particles, and in this case the correlation of apoB to LDL declines. The real LDL-C is lower and VLDL-C is higher. Thus lab LDL-C is less predictive, but apoB captures all the cholesterol on VLDL so better predictor

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Sam Tsimikas, MD

@Lpa_Doc

6 Feb

@stsimikas

1/23 Saturday Morning Class #14 Lp(a) and stroke @stsimikas @OxPL_apoB

Happy Saturday to all. Today, we will review evidence of Lp(a) as a risk factor for stroke in children, middle aged adults and elderly.

First, a graphic, note increase in papers in Medline since 1986

2/23 Useful fact: on Medline, searches for “Lp(a)”, “Lp (a)”, “lipoprotein(a)” or “lipoprotein (a)” don’t work. You need to use “lipoprotein a”. Medline has 8,759 citations on “lipoprotein a”. There are 611 citations on “lipoprotein a and stroke”, so 6.9% of citations

3/23 I have probably read only 25% of these (hopefully the key ones). If each takes 30 minutes on average to get the gist, it will take ~4400 hours to get through all of them, or 547, 8-hour days of just reading papers… so about 2 full years not including weekends. Daunting.

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