#1

Hi all, My first posting here, so a brief introduction: I am 38, male, a university professor with my lab researching myocardial infarction, and I’m interested in (anti-)aging. As a researcher, peer reviewer and associate editor, hopefully my contributions to this community can be useful. I’m not an aging specialist, but I’ve dipped my toes into that field and have my own personal interests. My background below:

Irresponsible youthful years
Around 15 years ago, during a bodybuilding bulking cycle, I did a bunch of blood tests. My total cholesterol was ~300mg/dl, with LDL-C of 200mg/dl. ALT/AST were also both 50+. I was chugging protein shakes, maltodextrin bulking supplements, eating lots of red meat etc. In the last 10 years, I had also experimented with a whole bunch of performance enhancing substances, including prohormones and various “research chemicals” off the Internet. So the time, I didn’t think much of it.

Growing up
When I my wife and I were thinking of having kids, I thought I should look after myself better. I was doing my postdoctoral training so I did another bunch of blood tests at our university hospital. Again, TC > 300 and LDL-C ~180. I also had an ultrasound which showed reasonably high amounts of fatty liver. I went to go see a regular family doctor. She said ‘you’re young, no real risk blah blah’. She even got out the QRisk calculator and showed my 10 year risk at <2%, told me to eat healthier, and shoved me out the door.

I showed my postdoc advisor (a professor and cardiovascular surgeon) the results and he got his cardiologist friend to take a look at me. We did more tests:

Total (all mg/dl): 275
LDL-C: 200
HDL-C: 50
Trigs: 63
A1C: 4.9
Fasting glucose: 85

We tried 3 months of lifestyle changes. I adhered to this 100%. Due to the bodybuilding background, I have excellent discipline in terms of tracking macronutrients and calories. This made little difference:

Total: 248
LDL-C: 184

Testing different pharmacological approaches
At this point, we’re confident this is not related to lfiestyle, so we started with 10mg Rosuvastatin (Crestor). Results after 3 months (and I resumed “normal” eating):
Total: 271
LDL-C: 201

This was totally ineffective. So, we added Ezetimibe 10mg/day:
Total: 119
LDL-C: 92
Trigs: 58
A1C: 5.2

Adding Ezetimibe was so effective, that I was curious whether Ezetimibe monotherapy would work.
Total: 168
LDL-C: 135
Trigs: 71

Ezetimibe monotherapy worked better than statin monotherapy, but this was not effective enough. Thus, we settled on taking both. I maintained this for 2 years and the average results of 6 blood tests:
Total: 132
LDL-C: 80

I’ve never had a single side effect. No muscle pain, GI distress or anything. I did another liver ultrasound, and the fat was completely gone, and my ALT and AST also came down to less than 30.

Another unpleasant realization
Later on, I attended a conference where the PESA study was being presented. That was a fairly terrifying presentation for me. At the banquet, I was luckily able to sit next to one of the senior authors. They convinced me that even my current LDL-C level of ~80 was still conferring some risk. They found that atherosclerosis can still progress with LDL-C levels higher than 40, and given my 30 years of high ApoB (ie already a large area under the curve), I might want to be even more aggressive.

A double whammy of risk factors
One of the PESA researchers told me that they found both Lp(a) and ApoB in some FH patients. I’d heard of this from Peter Attia, so I also tested Lp(a) based on their recommendation.

… 65mg/dl. Damn it. (For reference, the cutoff for “high” is 35…

This further convinced me that I needed to lower LDL-C more.

Getting aggressive
My cardiologist added a PCSK9i (I’ve used both Repatha and Praluent), 1x per month, taking ApoB down further. 7 days post injection, LDL-C is 28. And 29 days after, LDL-C is 55. Thus, this should represent the trough and peak levels. HBA1c still never moved from outside 4.8 to 5.1.

This has been very stable for the last 18 months, and I’ve again never had a single noticeable side-effect. I’d also mention that my ALT hasn’t been higher than 20 for the last year, and I had a record low of 12 one time. Last ultrasound showed a perfect liver, so clearly this combination has been immensely beneficial.

Family: parents and kids
I learned that my mother is one of 6 kids: 2 girls, 4 guys. All the guys are dead: all from AMI. The two girls are still alive. My father’s side is more mixed, but his brother (my uncle) had an MI at 42.

I emailed the PESA study researcher and asked their advice about testing my children and they said I should do it. My cardiologist arranged testing of my kid at 6 years old. Results: TC over 200, LDL ~160, Lp(a) 45, normal triglycerides. So almost certainly this is a form of FH. Based on guidelines, she will start treatment at 8 years old. My view is that we need to keep that area under the curve lower and that earlier intervention will give her the best head start possible.

Limitations of medical systems
When I started to learn more, I found that this stuff really isn’t anything crazy progressive, controversial or difficult. However, much of the current knowledge is not yet implemented. FH, ApoB, Lp(a) etc have been studies for decades, and the papers are published and well-cited. Yet, a GP looks at you as if you’re insane for asking for a Lp(a) test. FH is not particularly uncommon. However, these were only ever dealt with through me being proactive, and luckily having enough personal connections. If I was just some regular guy, with this risk profile, and I took my first GP’s advice, I’d potentially be having my first heart attack within the next decade.

I finally persuaded my mother to go and try and get tested. Turns out she was on 10mg Simvastatin repeating prescription, but hadn’t had a blood test for over a decade. It came back with TC almost 250. Her doctor’s cheap and lazy response was to increase her simvastatin from 10 mg to 20 mg, and asked her to come back in one year for another blood test. I told my mother to specifically mention Ezetimibe, and this GP told her that it was a bad and useless drug. He also poo-poo’d the idea that her 36yo son was using a PCSK9i. He told her that this was only for people who have had a heart attack already. Presumably he just sees a woman at 70+ and doesn’t see any point in trying to do anything. The problem is, parents have a really hard time appreciating that their kid might be better informed than their doctor they’ve seen forever. (I recall even Peter Attia’s parents ignore his advice!)

Some questions:

  1. Is there anybody with similar circumstances to me out there? Happy to share stories and advice, and I’d love to hear from you if you’re older than me.

  2. I’m strongly considering starting Rapamycin. Is anybody aware of any evidence from patients like me, or suitable/relevant animal models?

  3. I have never done a CAC. To my rationale, a zero score doesn’t mean no plaque exists, and it wouldn’t mean I should do less interventions. A positive score would cause a lot of worry and mental stress, and I’m already on ‘maximal’ therapy. Thus, I’m not sure what I would gain from knowing I have a score of 0, 5, or 500. I’m happy to be corrected on this, if anybody knows more. (Treadmill + ECG was normal, for whatever that’s worth.)

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#2

I hope it’s not a tendency, but just bad luck of having such irresponsible PCP for your mother and especially in her critical age when things start happening. My PCP watches closely all my tests results and pushes me to take action if needed. He’s really proactive. I can text him with any problem or question and he would reply within an hour or so. All my family, including grandchildren, are his patients.

Thank you for your post and welcome to the forum.

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#3

The EmpowerDX test can apparently see if you are a hyper-absorber of cholesterol, it seems you are based on the ezetimibe result.

If genetics interest you, you can always upload i.e Ancestry (a website) SNP’s (600-700k of them) to Nebula Genomics and it gives you percentiles with good gene studies (GWAS), I think I paid like $10 for one month then canceled, $50 for the Ancestry SNP’s. They offer WGS with all of the SNP’s on Nebula, though.

Doctors have insanely low knowledge or outdated risk calculators about this indeed, in fact in most places in the world I don’t think they even care if the patient aren’t beyond the reference interval in youth at 95th percent, i.e top 5% cholesterol, so 90-94% can have early events. Even those above 95 which is an arbitrary cut off that doesn’t even measure apoB, they might just say change diet and then forget about it. This is why CVD is primary cause of death, when it seems most cases can be prevented with early prevention, including those with a 50th percentile apoB. I’m thinking there will eventually be vaccines for this.

I have also thought the same, I’m guessing starting at 38 you’re much safer and the statin will probably calcify and stabilize plaque too, however a while ago I learned about one person’s approach based on CAC score, adding in aspirin, which I don’t know much about and opens a can of worms. Do you know what your untreated apoB was?

There is the usual thing of minimizing risk as much as possible to lower events with other factors, for example look at making sure BP is below 120/80, in optimal range, based on SPRINT trial IIRC. These effects are very likely compounding like lowering apoB. There are also other interesting preventative drugs maybe for lowering risk for CVD events further.

See these threads for BP:

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#4

Welcome!

Your story sounds too familiar to me. The much happier part for you is you discovered this and found your way to better advice long long long before I did.

I’m 58

Mother’s father had a lethal heart attack in his 40’s
My father had a heart attack in his 40’s.

At the time of his heart attack, when I was aprox 12, the only advice was to eat low-fat. As a result, my family mostly gave up red meat. I learned, at least for me, if you rarely eat red meat, you feel sick if you have it, so I mostly stopped. Then, for ethical reasons, I became a vegetarian at 25. For decades, I had a low fat diet because fat was bad, but I consumed tons and tons and tons of sugar because those were the Snackwells days that you are probably too young to even know about. But sugar was fine!!! (Oh, how I miss those days!)

My first cholesterol test in my 20s was around 200. I was told I was so lucky because my good cholesterol was high.

Fast forward to mid 30s and early 40s, my cholesterol has never gone much higher than 210-220’s ish, but during those two periods, I had two short experiments with low dose statins and simply hated them. I was even breaking up a pill and taking a fraction 3x per week, but I stupidly said I’d rather just die earlier. No alternative was given, and perhaps nothing else was even available at the time.

At aprox 42, when I asked my cardiologist if I should go vegan because I read the China study, he said your good cholesterol is good and you are not Chinese, so that is not applicable to you (I’d like to go back and punch him :slight_smile:

At some point in my early 40s I had a CAC and it was almost 400. I asked my new cardiologist if I’ll have a heart attack. He said it’s not ‘if’ but when. NICE! :). (I won’t bury the lead, I am still here!)

Then at aprox 50, during my executive physical, my new doc he said he didn’t believe my CAC score and wanted to do it again (I don’t look like a heart attack waiting to happen). It was almost 500.

On how some doctors feel your insides must match your outsides… multiple docs, over a few years, including those at the ER, missed my bad gallbladder (that turned gangrene from being ignored so long!) because I didn’t ‘look’ like I could have a bad gallbladder either.

My doc sent me to a local cardiologist who said you should go on Praluent which was brand new at the time. The problem was he kept putting me off to get free samples to give me. It was scary expensive when it first came out, even if still ridiculously priced. I eventually said, this is my life, I’m willing to pay until you get them. He said there was no urgency and to just wait.

Then, through a very lucky connection, I was able to become a patient of one of the top cardiologists at UCSF. The anger on his face when he heard the last doc was delaying my treatment was palpable. He was upset at the non treatment I had for so long. I’ve been on Repatha since. He also discovered I had an high Lp(a). Unfortunately he is no longer my cardiologist because he now mostly does research and only kept his more interesting cases, sigh. The good news is he thought I was healthy and boring!

I then read my Attia newsletter that talked about colchicine being approved, so I emailed my new cardiologist and he said ‘great idea’… I emailed my regular doc and he said ‘great idea’. I learned my health will be better served if I do my own research, sigh.
Then, I joined this forum and asked my doctor about the oft mentioned ezetimibe, and he said ‘great idea’. And a couple of months ago, I added bempedoic acid.

Over the last decade I learned more about nutrition and now I’m WFPB. Even though my issue is not my diet, I figure why not do everything I can, especially considering I have caused so much damage in the past.

I agree that if you are aggressively doing everything you can and no further motivation is needed, there is nothing to gain from having a CAC, unless there happens to be a happy surprise… but then you might stop being as vigilant, so that has a negative, too.

That was a very long winded way of saying “same, same”!

Yes, and even though I was criminally late to the party, like you, I realize most people never get the medical care we do. And like your parents, my much older brother and sister only got their first CAC last month, 15 years after mine, because they needed someone else to tell them they should. Each has been on statins but nothing else was ever mentioned to them. They only kept upping their dose. Because of me, and that means this forum, my sister is now on ezetimibe

I’ve done the treadmill and tests with contrast etc… everything looks fairly good. I am on rapa

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#5

Welcome! I see it like an apoE4 finding. If you have a CAC of 500, you are in an emergency situation in which you would take extraordinary measures to stop progression (side effects be damned). If you have a CAC of zero, you can take a balanced approach. The problem is most people fall in between and have to keep prioritizing carefully (aggressive-ish). But you might find useful information is the reason people do it. BTW, a test that also looks for soft plaques is better…provides more information (sometimes a CAC of zero doesn’t tell you enough)

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#6

Well i’m 72 and have no history of CVD. My Cholesterol has been close to 300 all my life and LDL over 180. But my inflammation has been low, I exercise (mountain bike, Carol bike, hiking, skiing).
Tried a statin a couple of times for a week or two and hated it - so no treatments.

My parents were both on statins (don’t know for how long) Father got diabetes, mother dementia. Neither ever had a heart event in their lives

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#7

My mother, 92, has tc 300+. Doesn’t want to take statins. Doesn’t have dementia. Her heart is healthy. And overall she’s doing ok.

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#8

Heavy metals contribute to heart disease. I had a high lead burden and a CAC of 285. No big reason or way I can see that I should have had this, but there it is. I found out by doing a chelation challenge. EDTA takes forever and costs a lot, there are various oral chelation agents, I use DMSA now. Also it’s a no brainer to use Pectasol since blocking galectin 3 protects against cancer, heart disease and binds heavy metals.

Gotu Kola and marine pine bark protect against heart disease. Cheap and they work, this is in the literature.

In case you don’t know how to search this site:

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#9

You can hope you are lucky and high cholesterol won’t give you a heart attack or stroke. Or you can recognize the risk and do something about it so that you don’t rely on luck.

If you are a serious longevist, you should know which route to take.

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#10

That is in response to whom?

#11

This is in response to everyone who reads it.

There is a reason CVD is the number one killer in the world. If you hope to live a long long time, you need to tame this beast. It grows stronger (and you grow weaker) every day that you ignore it.

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#12

“Results after 3 months (and I resumed “normal” eating):
Total: 271
LDL-C: 201
This was totally ineffective.”

You blame the drug and not at all the resuming of “normal” eating, which started to have an effect, that then completely disappeared after resuming “normal” diet, and from then on it is all on diverse drugs, not diet. Sure, pill popping is far more convenient than diets, but if in the end it only lowers some numbers well known since they react to popular drugs, but other numbers perhaps more important do not improve, well, maybe the easy way is not the right path.

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#13

Thanks Lara. Happy to hear you have a great doctor! Yes, I think part of it is bad luck. But, without making this a political thread, it’s illustrative of the terrible state of UK “healthcare” right now. Unless you’re actually injured dying, there is very little interaction with the medical system. Very little preventative or proactive medicine. A lot of it is due to where you live - some postcodes have great care, and others have almost none.

Yes, exactly. And I can understand that a family doctor is bombarded with everything from cholesterol, to mental health, to joint aches, to infectious diseases. The problem is the dismissive/elitist/snobby nature of brushing off concerns - especially when it comes from an educated patient.

Thanks for the comment. I don’t know what my untreated ApoB was, but it can’t have been pretty! Aspirin is a fair point, and perhaps something to look at - thanks!

And I do my best to control other risks like BP, I never smoke, have given up almost all alcohol etc.

Thanks for sharing your story Beth. I enjoyed reading it, though it’s obviously quite a frustrating story. I guess I’m lucky that statins have no discernible side effects, either in how I feel or how biomarkers move.

If it is genetic, the effect of food on the biomarkers seems minimal. However, a WFPB diet should be good in plenty of other ways, not just LDL-C and CVD.

Did Rapa do/change anything as far as you’re aware?

Thanks Joseph. Could you please define balanced vs extraordinary. I’m not on statin/Ezetimibe/PCSK9i and my LDL-C is never higher than 50. I’m not sure what else I could add into the extraordinary pile.

Hi Paul, yeah LDL-C (or ApoB cholesterol) is interesting. I am firmly convinced that it is causative and required for atherosclerosis. However, it’s not the only factor, and there are people walking around with sky high serum LDL-C who never get atherosclerosis. Presumably there are other factors giving them resistance. (There are also people with lower LDL-C who get rampant ASCVD, suggesting greater susceptibility).

Your level of 180 is very high. Did you ever check your arteries - like carotid ultrasound, coronary CT, calcium scan etc? If you have a healthy lifestyle and weight (which obviously you do), and your numbers are still that bad, there’s a reasonable probability you also a form of FH.

If I were in your shoes, no matter how good my lifestyle, I wouldn’t be able to accept walking around with a TC of 300 unless I had a totally negative CAC. If it came back zero, I guess you could consider yourself resistant to ASCVD. But I wouldn’t take that risk without evidence.

Thanks for sharing your thoughts and the interesting paper. I’ll look into it some more, though the patient population isn’t really like me. That said, these are a lot more “experimental” than statin/zetia/PCSK9i.

There’s no “blame” here. Statin monotherapy simply doesn’t work for some people. That’s well-documented, especially in genetic conditions. Based on the literature, 10mg Rosuvastatin should produce at least a 30% lowering. Mine was not even remotely close to that.

And “normal” diet doesn’t mean I suddenly started living off hot dogs. It just means not counting every calorie, and not saying no to birthday cake. I had also found that eating “clean” made very little difference to my numbers anyway. And my kid, aged 6, has LDL-C more than 2x higher than normal - clearly it’s genetic because her diet, exercise etc is fantastic.

In principle though, I don’t see what’s wrong with popping the pills. You said it like it’s a shortcut which is morally questionable. However, these medications are super safe, used by millions, better studied than almost any other medication. They’re a LOT better studied than any sort of supplement, dietary intervention or alternative treatment.

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#14

“10mg Rosuvastatin should produce at least a 30% lowering. Mine was not even remotely close to that.”
because… you returned to normal diet, is what you wrote, but you do not take that into account, but only blame the drug being insufficient, there is no misunderstanding, you wrote it now the second time, confirming it. After all, that diet started to work, but you focus on drugs. Now you are stuck. I wonder why. Solution… pop some rapa on top!

#15

“Extraordinary” measures = apoB <40; doing whatever it takes to get there. The kitchen sink approach. Adding dosage or additional interventions. Maybe try supplements for icing on the cake: Pantothenine, Bergamot. Definitely lower saturated fat intake. Look for threads here on Lp(a) reduction.

“Balanced” approach would be getting into normal ranges and focusing on overall health via lifestyle. …Avoiding side effects from drugs that interfere with quality of life and exercise and sleep.

Good luck.

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#16

@Joseph_Lavelle
I haven’t heard of bergamot or panthothenine.

My latest labs have my ApoB at 43, but my goal is 30… you think I should give these two a whirl?

Also @relaxedmeatball This reminded me to mention Amla extract. I once saw a nutrition facts org video showing it helps reduce cholesterol, so i take it. I have no idea if it does anything, but I haven’t seen comments to the contrary and it seems harmless… maybe a waste of money? Also, on rapa, I started it last spring at 6mg per week. The only thing I”m sure of is it somehow magically changed my sleep. I’m a lifelong insomniac who is no longer a lifelong insomniac :). As you can imagine, nothing has changed the quality of my life more profoundly than rapa.

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#17

That’s a bad source, and if supplements worked they would be FDA approved because they had demonstrated efficacy and safety. :wink:

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#18

Are you saying you only take things FDA approved for efficacy? I’m thinking I misunderstand you because that would make you different from 99.99999% of the others here.

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#19

All of the supplements I take now are FDA-approved drugs: vitamin D, calcium, vitamin B12. The supplements you listed are not.

If I were to take a drug with unknown efficacy I could repurpose a still FDA-approved drug.
If I would take a supplement without FDA approval I wouldn’t take it to replace a FDA-approved drug, that’s foolish in my opinion unless you can’t get the drug itself.

Listing supplements for lowering cholesterol without FDA-approval I hope people only do it because they can’t get the approved drug. That’s all.

#20

I cannot comment on the benefits or costs of very low aboB but these two supplements have been mention on this forum as useful for lowering apoB. I have taken them in the past without any issue. The benefits are small if any for me (too small to notice among all the noise).

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