General Research - Ancillaries

[egruberman]

I was going to say, at that level of cholesterol and for that long, you should probably take more aggressive measures

Agreed. The calcium score will give some indication of how aggressive an intervention is warranted. There are several genetic variants that provide protection from endothelial damage, even in the presence of elevated atherogenic particles. I don’t know that they’ve been classified very well, but I’ve seen anecdotal reports of people with very high ApoB and a zero calcium score.

Lucky them.

Speaking of…. I finally got the results of my whole genome sequencing from Nebula genomics. I should share that experience and results. No surorise, elevated ApoB showed up as highly probable.

 

[Sicsemptyran]

Agreed. The calcium score will give some indication of how aggressive an intervention is warranted. There are several genetic variants that provide protection from endothelial damage, even in the presence of elevated atherogenic particles. I don’t know that they’ve been classified very well, but I’ve seen anecdotal reports of people with very high ApoB and a zero calcium score.

Lucky them.

My wife’s father has a sky high Lp(a) and ApoB, never has had any interventions for it, and has a 0 CAC in his late 60s. No relative of his has ever died of heart disease despite every other member of his family having been chain smokers and mostly obese alcoholics. He takes great care of himself and given those genes I imagine will live to a ripe old age, despite bloodwork that would end my time here before the age of 60.

Can only work with the genes we got unfortunately!!

 

[Avies48]

Probably time to schedule a CT-CAC and get your calcium score. The procedure is cheap. When you choose a lab, make sure you ask about the radiation dose. Most are low dose these days which is around 1 millisievert or lower. If higher than 1.5mSv, I’d look elsewhere.

Calcium cac ran a while back… 8-9-2024

The circumflex artery is a branch of the left coronary artery that supplies oxygenated blood to the left side and back of the heart, particularly the left ventricle and left atrium. It plays a crucial role in the heart's blood supply and can be involved in coronary artery disease if plaque builds up.


Advanced 3DWorkstation. Radiation dose: Total
DLP 166.00 mGy-cm; CTDIvol 12.36 mGy

 

[egruberman]

Calcium cac ran a while back… 8-9-2024

That’s recent enough to give a good indication if plaque burden. Generally one would only want to repeat such a thing every few years.

Your score is under 10, which is in the margin of error. Could be a little calcified plaque, could be none. In either case, congratulations on having some good genetics.

In terms of interventions, that’s really up to you and what you want to deal with. If you are otherwise healthy, ie HbA1C is good, blood pressure is good, regular cardio and a decent diet then I wouldn’t view pharmaceutical intervention as strictly necessary. If the elevated ApoB concerns you, you could experiment with some combination of low dose Rosuvastatin, ezetimibe and bempedoic acid.

Peter Attia had a similar result on a CAC. Maybe a bit higher but still around 10 or so. He had elevated lipids as well. He got on a statin. Eventually he repeated the test and got a zero result and, I think eventually settled on bempedoic acid mono-therapy.

 

[Nidus]

That’s recent enough to give a good indication if plaque burden. Generally one would only want to repeat such a thing every few years.

Your score is under 10, which is in the margin of error. Could be a little calcified plaque, could be none. In either case, congratulations on having some good genetics.

In terms of interventions, that’s really up to you and what you want to deal with. If you are otherwise healthy, ie HbA1C is good, blood pressure is good, regular cardio and a decent diet then I wouldn’t view pharmaceutical intervention as strictly necessary. If the elevated ApoB concerns you, you could experiment with some combination of low dose Rosuvastatin, ezetimibe and bempedoic acid.

Peter Attia had a similar result on a CAC. Maybe a bit higher but still around 10 or so. He had elevated lipids as well. He got on a statin. Eventually he repeated the test and got a zero result and, I think eventually settled on bempedoic acid mono-therapy.

I am not sure if i missed it (feel free to call me a idiot for that) but do supplements like K7 help with plaque? Like is there anything that could prevent or dissolve buildup plaque?

 

[egruberman]

I am not sure if i missed it (feel free to call me a idiot for that) but do supplements like K7 help with plaque? Like is there anything that could prevent or dissolve buildup plaque?

Vitamin K2 (MK7) has been shown in some trials to slow the progression of atherosclerotic plaque. The data is not conclusive, however. There are several trials that show no effect.

For plaque regression it seems that one must achieve a very low level of LDL as was done with a PCSK9 inhibitor plus statins in the GLAGOV trial. Here's a summary:

Cleveland Clinic-Led Study Shows Reversal of Coronary Plaque Buildup With Injectable Cholesterol Drug

NEW ORLEANS: Cleveland Clinic researchers have found that adding the injectable cholesterol-lowering drug evolocumab (Repatha) to full doses of statin drugs reversed the buildup of cholesterol plaques in the coronary artery walls after 18 months of treatment. Patients receiving the combination...

newsroom.clevelandclinic.org

JACC published a review in 2022 on reversal here:

https://www.jacc.org/doi/10.1016/j.jacc.2021.10.035

Indicates pretty much the same thing.

The DANCODE trial is underway to directly measure whether K2 lowers CAC scores:

The DANish COronary DEcalcification (DANCODE) Trial

1. Abstract Introduction Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. A substudy in the recent Danish study, AVADEC, suggested a protective role of supplementation with vitamin K2 and D...

ctv.veeva.com

There was evidence of plaque regression demonstrated as early as 2005ish in the REVERSAL trial. They used high doses of statins to achieve very low LDL levels and subsequently saw a reduction in plaque volume. I posit that similar results can be achieved today using a poly-pharmacy approach obviating the need to use a high intensity statin. The review by JACC in 2022 suggests as much.

Presently, I take 10mg Rosuvastatin, bempedoic acid, ezetimibe, and Repatha. My last LDL-C measurement was 17mg/dL

Of note is the fact that all of these trials demonstrated a reduction in plaque volume, but none of them measured calcified plaque, which is only a crude measure of plaque burden in any case. It represents the end stage of plaque progression and is easy to spot on a CT scan. If it's there, you know that something bad has happened. However, once conditions that led to its existence are reversed, soft plaque may diminish, but the calcified plaque will not. Risk of a MACE will have been reduced, but not indicated in a subsequent CT-CAC.

If we could all get CT-A that'd be for the best. Unfortunately, it's not cheap and insurance won't cover it unless you're nearly dead already.

 

[Nidus]

Vitamin K2 (MK7) has been shown in some trials to slow the progression of atherosclerotic plaque. The data is not conclusive, however. There are several trials that show no effect.

For plaque regression it seems that one must achieve a very low level of LDL as was done with a PCSK9 inhibitor plus statins in the GLAGOV trial. Here's a summary:

Cleveland Clinic-Led Study Shows Reversal of Coronary Plaque Buildup With Injectable Cholesterol Drug

NEW ORLEANS: Cleveland Clinic researchers have found that adding the injectable cholesterol-lowering drug evolocumab (Repatha) to full doses of statin drugs reversed the buildup of cholesterol plaques in the coronary artery walls after 18 months of treatment. Patients receiving the combination...

newsroom.clevelandclinic.org

JACC published a review in 2022 on reversal here:

https://www.jacc.org/doi/10.1016/j.jacc.2021.10.035

Indicates pretty much the same thing.

The DANCODE trial is underway to directly measure whether K2 lowers CAC scores:

The DANish COronary DEcalcification (DANCODE) Trial

1. Abstract Introduction Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. A substudy in the recent Danish study, AVADEC, suggested a protective role of supplementation with vitamin K2 and D...

ctv.veeva.com

There was evidence of plaque regression demonstrated as early as 2005ish in the REVERSAL trial. They used high doses of statins to achieve very low LDL levels and subsequently saw a reduction in plaque volume. I posit that similar results can be achieved today using a poly-pharmacy approach obviating the need to use a high intensity statin. The review by JACC in 2022 suggests as much.

Presently, I take 10mg Rosuvastatin, bempedoic acid, ezetimibe, and Repatha. My last LDL-C measurement was 17mg/dL

Of note is the fact that all of these trials demonstrated a reduction in plaque volume, but none of them measured calcified plaque, which is only a crude measure of plaque burden in any case. It represents the end stage of plaque progression and is easy to spot on a CT scan. If it's there, you know that something bad has happened. However, once conditions that led to its existence are reversed, soft plaque may diminish, but the calcified plaque will not. Risk of a MACE will have been reduced, but not indicated in a subsequent CT-CAC.

If we could all get CT-A that'd be for the best. Unfortunately, it's not cheap and insurance won't cover it unless you're nearly dead already.

Very interesting read! Thank you for putting this together and providing sources right away! I also came across Repatha but that is nearly impossible to source and insanely expensive (starting prices i came across were about 1.5k for 6-8 pens)
Don't bempedoic acid and ezetimibe work through the pathway?

Also currently on 10mg ezemtibe and atorvastin (atozet 10mg each), so wondering if it makes sense to add in bempedoic acid?

On top of that i also run injectable Carnitine which helped me a bit too but mostly use that for the Tryg.

 

[Avies48]

That’s recent enough to give a good indication if plaque burden. Generally one would only want to repeat such a thing every few years.

Your score is under 10, which is in the margin of error. Could be a little calcified plaque, could be none. In either case, congratulations on having some good genetics.

In terms of interventions, that’s really up to you and what you want to deal with. If you are otherwise healthy, ie HbA1C is good, blood pressure is good, regular cardio and a decent diet then I wouldn’t view pharmaceutical intervention as strictly necessary. If the elevated ApoB concerns you, you could experiment with some combination of low dose Rosuvastatin, ezetimibe and bempedoic acid.

Peter Attia had a similar result on a CAC. Maybe a bit higher but still around 10 or so. He had elevated lipids as well. He got on a statin. Eventually he repeated the test and got a zero result and, I think eventually settled on bempedoic acid mono-therapy.

Thanks although my genetics honestly suck, had a grand parent who had horrible cholesterol and had 2 massive heart attacks and major surgeries… due to them, died during the last surgery… i havent done cardio in about 10+ yrs tbh… but im also not on any aas, never have been. Always trt due to teste’s not working… and i quit trt in early 2014ish… after being on trt for 10 yrs give or take a few….just started up agin this past weekend… on trt…

Statins i cannot take so either zetia, ezetimibe and bempedoic acid, or just see how long i can go with out taking anything…

Want to get a full body scan to see if they find anything in lower extremities, such as plaque, clogged areas etc…

 

[Avies48]

Very interesting read! Thank you for putting this together and providing sources right away! I also came across Repatha but that is nearly impossible to source and insanely expensive (starting prices i came across were about 1.5k for 6-8 pens)
Don't bempedoic acid and ezetimibe work through the pathway?

Also currently on 10mg ezemtibe and atorvastin (atozet 10mg each), so wondering if it makes sense to add in bempedoic acid?

On top of that i also run injectable Carnitine which helped me a bit too but mostly use that for the Tryg.

If u have insurance, i went thru push health tele-health and got repatha script thru them… insurance said yes aince i cannot take statins… first time i clotted using 5 mlg of crestor thru the first 2 weeks….i never touched the repatha injections i got sitting in my cupboard…as ive read some horror stories…

 

[egruberman]

I also came across Repatha but that is nearly impossible to source and insanely expensive (starting prices i came across were about 1.5k for 6-8 pens)
Don't bempedoic acid and ezetimibe work through the pathway?

If you're in the US and can get an Rx for Repatha, you can apply for their copay card. They're pretty generous with it.

Bempbedoic acid is a pro-drug that inhibits an enzyme (ACL) required for cholesterol synthesis. As a result of inhibited cholesterol synthesis, there is an increased expression of LDL receptors in the liver increasing LDL clearance.

Bempedoic acid is upstream of HMG-CoA reductase, another enzyme required for cholesterol synthesis, which is inhibited by statins. As a result, there is a complementary effect. More LDL receptors are expressed in the liver and LDL clearance is increased as a result.

Ezetimibe inhibits absorption of cholesterol in the intestine decreasing cholesterol stores in the liver. Guess what that does? Increase LDL expression in the liver which increases LDL clearance from the blood stream.

What should be fairly obvious is that these mechanisms of action are complementary and there are no detrimental interactions The fact that the ACC continues to push high intensity statin mono-therapy boggles the mind.

Also currently on 10mg ezemtibe and atorvastin (atozet 10mg each), so wondering if it makes sense to add in bempedoic acid?

That depends on your approach. My approach is thus: plaque is present, ergo, smash LDL in as much as I can. I would add bempedoic acid if I were you. If you can't get insurance to cover it, it is available cheaply through Indian pharma places on Meso.

Statins i cannot take so either zetia, ezetimibe and bempedoic acid, or just see how long i can go with out taking anything…

Uh... Probably not a great strategy. A combo of ezetimibe and bempedoic acid should work pretty well.

.i never touched the repatha injections i got sitting in my cupboard…as ive read some horror stories…

I've had no issues. Some site reactions, but otherwise fine. Adverse side effects for any lipid management drug seems to be overstated.

Hell, there's a large community of people firmly of the opinion that lipids don't matter and lipid management drugs are a consipiracy.

 

[Nidus]

If you're in the US and can get an Rx for Repatha, you can apply for their copay card. They're pretty generous with it.

Bempbedoic acid is a pro-drug that inhibits an enzyme (ACL) required for cholesterol synthesis. As a result of inhibited cholesterol synthesis, there is an increased expression of LDL receptors in the liver increasing LDL clearance.

Bempedoic acid is upstream of HMG-CoA reductase, another enzyme required for cholesterol synthesis, which is inhibited by statins. As a result, there is a complementary effect. More LDL receptors are expressed in the liver and LDL clearance is increased as a result.

Ezetimibe inhibits absorption of cholesterol in the intestine decreasing cholesterol stores in the liver. Guess what that does? Increase LDL expression in the liver which increases LDL clearance from the blood stream.

What should be fairly obvious is that these mechanisms of action are complementary and there are no detrimental interactions The fact that the ACC continues to push high intensity statin mono-therapy boggles the mind.



That depends on your approach. My approach is thus: plaque is present, ergo, smash LDL in as much as I can. I would add bempedoic acid if I were you. If you can't get insurance to cover it, it is available cheaply through Indian pharma places on Meso.



Uh... Probably not a great strategy. A combo of ezetimibe and bempedoic acid should work pretty well.



I've had no issues. Some site reactions, but otherwise fine. Adverse side effects for any lipid management drug seems to be overstated.

Hell, there's a large community of people firmly of the opinion that lipids don't matter and lipid management drugs are a consipiracy.

Thank you for the incredible detailed answer, appreciate that!

I am from Central Europe, Bempbedoic acid here costs about 100€ for 28 pills at 180mg. Will look into sourcing some but seems very difficult to get overall compared to the US.

 

[Avies48]

Ill see about getting some of the 2 u mentioned

Any muscle issues on the acid and or esti?

 

[egruberman]

I am from Central Europe, Bempbedoic acid here costs about 100€ for 28 pills at 180mg. Will look into sourcing some but seems very difficult to get overall compared to

There are several vendors of Indian Pharma on Meso. Some of them offer “Bempesta” quite cheaply. I think there may be a combo with ezetimibe as well. In the US it’s very expensive as well.

Ill see about getting some of the 2 u mentioned

Any muscle issues on the acid and or esti?

The prescribing information for bempedoic acid in the US mentions “tendon rupture” as a potential side effect. This occurred in trials only in combination with high intensity statins and in very old people. As for myalgia, which some on statins experience, there’s little to no incidence reported.

Hilariously in one trial, myalgia was reported in ~3% of patients on bempedoic acid after which they discontinued treatment. Myalgia was reported in ~%6 of the placebo group, after which they discontinued “treatment”

 

[Nidus]

There are several vendors of Indian Pharma on Meso. Some of them offer “Bempesta” quite cheaply. I think there may be a combo with ezetimibe as well. In the US it’s very expensive as well.



The prescribing information for bempedoic acid in the US mentions “tendon rupture” as a potential side effect. This occurred in trials only in combination with high intensity statins and in very old people. As for myalgia, which some on statins experience, there’s little to no incidence reported.

Hilariously in one trial, myalgia was reported in ~3% of patients on bempedoic acid after which they discontinued treatment. Myalgia was reported in ~%6 of the placebo group, after which they discontinued “treatment”

Managed to source bempedoic acid at 180mg with 10mg Ezemtibe and 5mg Rosuvastatin.

Will continue running this alongside with injectable Carnitine (600mg) for a month and then pull bloods.

Also running Tirza, Metformin, Jardiance and pioglitazone.

Thank you again @egruberman for the incredible detailed insight you provide and your advice!

 

[Avies48]

Managed to source bempedoic acid at 180mg with 10mg Ezemtibe and 5mg Rosuvastatin.

Will continue running this alongside with injectable Carnitine (600mg) for a month and then pull bloods.

Also running Tirza, Metformin, Jardiance and pioglitazone.

Thank you again @egruberman for the incredible detailed insight you provide and your advice!

Hory fuck thats a lot of low blood sugar id see if i ever used tirz met and jarda at the same time, id prolly be dead tbh

Have routine bw done whilst on the bemp acid. And keep an eye on that bs and insulin with all those beetus meds… tirz actually helps with a lot and some have seen the need to reduce other meds once on tirz…

 

[Nidus]

Hory fuck thats a lot of low blood sugar id see if i ever used tirz met and jarda at the same time, id prolly be dead tbh

Have routine bw done whilst on the bemp acid. And keep an eye on that bs and insulin with all those beetus meds… tirz actually helps with a lot and some have seen the need to reduce other meds once on tirz…

High Insulin resistance runs in the family, even the leanest person has a Homa Index of 3.0 (anything above 2.0 is considered pre-diabetic here).

Got a gene according to my doc that causes all kinds of tissue to have a strong resistance towards insulin, so despite having a great hba1c my homa index always has been absolute shit.

I improved mine already a lot but i am hoping to get it down further while also loosing a lot of fat. Long journey but a needed one.

 

[Avies48]

High Insulin resistance runs in the family, even the leanest person has a Homa Index of 3.0 (anything above 2.0 is considered pre-diabetic here).

Got a gene according to my doc that causes all kinds of tissue to have a strong resistance towards insulin, so despite having a great hba1c my homa index always has been absolute shit.

I improved mine already a lot but i am hoping to get it down further while also loosing a lot of fat. Long journey but a needed one.

Damn how did u get tested for that? Great that it isnt an issue and they are spending years truin to figure it out, as thats what usually occurs

 

[Nidus]

Damn how did u get tested for that? Great that it isnt an issue and they are spending years truin to figure it out, as thats what usually occurs

Genetic Testing panel, tests stuff for genes that are known to induce illnesses or family related stuff like cancer, tumors, Alzheimer and so on. Quite expensive but very interesting!

 

[Avies48]

Genetic Testing panel, tests stuff for genes that are known to induce illnesses or family related stuff like cancer, tumors, Alzheimer and so on. Quite expensive but very interesting!

Hmm over seas or stateside? Ive always done a few of these to see whats up and always like haven options

 

[Nidus]

Hmm over seas or stateside? Ive always done a few of these to see whats up and always like haven options

I am from Europe, private clinics offer that here, costs around 200-900€ depending how crazy you wanna go.

I basically have high risk of NAFD, High Cholesterol and shitty Insulin resistance. Gotta love genetics but at least no additional Alzheimers risk