心血管健康

[AnUser]

You need visions, a hot chili stew… The Teachings of Don Juan.

[ng0rge]

@AnUser

The Teachings of Don Juan.

I grew up with the Teachings of Don Juan (I live close to Yaqui country and have been to the peyote fields) and also the teachings of Adele Davis (raw liver didn’t give me visions, but the puking was the same). I’ve had many visions (may be having one now) so I’m just as reliable as an A.I.

For @AnUser , just went to Lucha Libre here last night.

[AnUser]

@ng0rge

For @AnUser , just went to Lucha Libre here last night.

Looks like they’re pushing an apoB particle into the arterial wall.

[mccoy]

@AnUser, Dr. Caldwell Esseltsyn should have been a preacher. He sees olive oil (and all other oils) as the devil, and a very low fat vegan diet as the Saviour of the world.

Adopting a fat and oils-free diet will deliver humanity from evil.

[adssx]

@ng0rge

If someone has gone untreated and shows a LDL-C greater than 190 mg/dL in their 50s and zero plaque, I would want to know how that could happen. The rules of lipidology say that ApoB is independently causal for plaque, both necessary and sufficient. So, how have these people, a small minority of the population but still a significant number, gone decades with high ApoB and zero plaque?

@ng0rge: what’s the paper URL?

I don’t think I read the study but:

1. They might have high LDL-C but low ApoB
2. We don’t know their history. They might be at 190 mg/dL now but maybe for their whole life before they were at 70 mg/dL and for whatever reason it recently increased. So they have less lifetime exposure than someone at 100 mg/dL their whole life.
3. Other metrics matter: insulin resistance, BP, hsCRP, Lp(a): do we have that data?
4. What about men only? Women have some protection conferred by their estrogens.

[adssx]

Advancements in risk stratification and management strategies in primary cardiovascular prevention 2024

This paper sums up the “mainstream” view:

For me the post interesting part is 4.2.5 Anti-inflammatory drugs:

There is increasing evidence regarding the relationship between the use of immunomodulating drugs and favourable cardiovascular outcomes, mainly in patients with established ASCVD. The first anti-inflammatory therapy approved for secondary ASCVD prevention is low-dose colchicine, which is a broad anti-inflammatory drug. Trials like COLCOT and LoDoCo2 have demonstrated reduced MACE in CAD patients treated with low-dose colchicine compared with those on placebo. In this setting, colchicine may also promote plaque stabilisation. A recent study has demonstrated reductions in LAPV, a measure of plaque stability, as assessed by CCTA in patients receiving colchicine on top of optimal treatment compared to those receiving standard-of-care treatment; of note, overall atheroma plaque volume was not different between groups. According to current guidelines low-dose colchicine (0.5 mg daily) may be considered for secondary prevention especially in patients with recurrent ASCVD events under optimal medical therapy or insufficiently controlled risk factors after acute coronary syndrome episodes. However, data on the impact of colchicine use on primary prevention is still lacking. Similarly, while methotrexate and canakinumab have shown promising results in secondary ASCVD prevention, their efficacy remains uncertain, and benefit may be restricted to selected patients such as patients with heightened inflammation (hsCRP>2 mg/ml) or TET2-driven CHIP. The ongoing ZEUS trial (NCT05021835) investigating IL-6 inhibition in ASCVD patients with CKD may provide further valuable insights into immunomodulatory approaches for ASCVD management

And mixed results on omega 3:

Another potential strategy is to use 3-polyunsaturated fatty acids (3-PUFA, omega-3 fatty acids), particularly the highly purified, stable eicopentaeonoic acid (EPA)-derivative icosapent ethyl. However, it is noteworthy that while the REDUCE-IT trial demonstrated cardiovascular benefits, these benefits were not statistically significant in the primary prevention subgroup. Conversely, the STRENGTH trial failed to show a significant reduction in MACE among high-risk patients treated with EPA, leading to a downgrading of the recommendation for EPA use to class IIb in the 2021 ESC prevention guidelines. On the other hand, several studies have reported plaque regression or increased stability following EPA use in patients with coronary atherosclerosis

So plaque regression does not lead to MACE reduction?

[AnUser]

Also survivorship bias, the proportion without CAC is higher because possibly those who had developed it earlier died.
The paper is here:

Coronary Plaque, LDL-C Levels, and Rates of CVD Events Among Symptomatic Adults

[CronosTempi]

OK AnUser, but the findings in your study were in symptomatic individuals. What does that mean? It’s hard to imagine that high LDL levels in zero CAC score
asymptomatic individuals result in worse outcomes compared to symptomatic individuals.

To me a more interesting question is to compare two matched cohorts of symptomless individuals, both zero CAC score, but one with lifelong very elevated LDL levels, the other low-average LDL levels, but not from CV outcomes, MACE, but all cause mortality.

We know that very high LDL levels are also detrimental in other health outcomes, such as cancer, dementia, and so on. So the question becomes *for those lifelong high LDL but zero CAC score" - what are other health outcomes, all cause mortality (ACM). Because it is possible that while they may escape CVD MACE mortality/morbidity outcomes, they nonetheless experience increased HR for ACM based on other health burdens (cancer, dementia etc.). But if they have NO ACM penalty, then they got away scot free with their lifelong high LDL levels. This is of personal interest to me, because I’m one of those zero CAC score at age 65, but lifelong - and until age 61 unmedicated - high LDL, ApoB, Lp(a) levels, and am asymptomatic for any CVD (and no CVD detected).

Personally, I’m taking no chances, and will attempt to drastically lower my LDL (to at least below 70), because in recent years, I’ve moved to pre-diabetic status (FBG and A1c) and prehypertensive. So my new stack will be (in addition to the current 10mg/day atorvastatin), bemp+eze, empag, teli, and rapa. Because my suspicion is that even if I can get away with no CVD, these increasing co-morbidities from becoming diabetic and hypertensive, will have a severely limiting impact on longevity (and healthspan). Unfortunately, despite heroic efforts at lifestyle and diet optimization, my numbers are only getting worse, so for me, my last ditch efforts will be “better living through chemistry”… polypharmacy, here I come!

[Virilius]

Develop a drug that simulates that effect and stack it with a statin for dual protection.

[ng0rge]

@CronosTempi

This is of personal interest to me, because I’m one of those zero CAC score at age 65, but lifelong - and until age 61 unmedicated - high LDL, ApoB, Lp(a) levels, and am asymptomatic for any CVD (and no CVD detected).

This is what interests me. Do you have any possible explanation for your zero CAC score with high LDL-C, Apob and Lp(a) levels? At what age did you first measure LDL-C? Have you tested for soft plaque (non-calcified) with a CIMT test or CCTA? Any genetic reason that you would be resistant to plaque?
Lowering ApoB seems to be the safest strategy - if there are no negative side effects (which generally appears to be the case). But it’s a personal decision. The guidelines say for a person with no plaque and high LDL-C that statins are optional. Certainly if you don’t take lipid lowering interventions, you should get at least yearly scans for plaque. As you said aging and the development of other risk factors - pre-diabetic and pre-hypertensive - are real causes for concern and should be dealt with independently in any case. There is likely no downside to lowering ApoB.

[ng0rge]

@adssx

• They might have high LDL-C but low ApoB
• We don’t know their history. They might be at 190 mg/dL now but maybe for their whole life before they were at 70 mg/dL and for whatever reason it recently increased. So they have less lifetime exposure than someone at 100 mg/dL their whole life.
• Other metrics matter: insulin resistance, BP, hsCRP, Lp(a): do we have that data?
• What about men only? Women have some protection conferred by their estrogens.

Good questions and I would be interested in your critique of the study (Danish).
We don’t know their lifetime exposure and if it were just a few people, then as you said, their ApoB could have only recently gone up. But with these numbers, it’s more likely that most of them didn’t just recently have a dramatic change.

@adssx

Other metrics matter: insulin resistance, BP, hsCRP, Lp(a)

Yes, but these would all drive up their risk, not down.

@adssx

Women have some protection conferred by their estrogens.

Yes, until menopause.
If you’re interested in the science of how plaque starts (not everyone is) and not just lowering ApoB and how low you should go, you should take a look at the study and the other thread.

https://spotify.localizer.co/t/the-ldl-kingpin-theory-one-ring-to-rule-them-all-lmhr/15982?u=ng0rge

The more I look into it, the more evidence I see that high ApoB and zero plaque affects a small minority of the population but not negligible. It’s just not commonly tested, usually with high ApoB you just take medication - plaque is unknown. But as they scan more for plaque, they’re seeing a it’s not that rare to have high ApoB zero plaque (we don’t know the numbers).

[Virilius]

I see three possible approaches for future medical trials.
a) increase apoA (not just HDL-C)
b) strongly decrease inflammation markers (something statins and ezetimibe already do, just better)
c) “strengthen” cell walls (whatever that means in practice)

[ng0rge]

@Virilius

a) increase apoA (not just HDL-C)

Dayspring made an interesting point about ApoA1 (which I didn’t know) in his recent presentation.

Evolution and Interpretation of Lipid and Lipoprotein Biomarkers Related to...

He says that what you need to know is HDL particle count and there may be up to 5 ApoA1s on one HDL particle.

[Davin8r]

Would be nice to see a clinical trial with 3 groups (in addition to placebo), all of whom have elevated ApoB and hs-CRP: 1) a pure ApoB-lowering group using PCSK9i, not statins/ezetimibe/BA due to their anti-inflammatory effects 2) a pure anti-inflammatory group (colchicine only, no lipid lowering) and 3) combo of both.

That way we could tease out the relative importance of each approach. Might be impossible to run a study with a high-lipid group without treating their lipids, though

[CronosTempi]

I first found out I had high cholesterol, because I decided to have a physical before visiting Eastern Europe back when they were still under communism… my idea was to make sure I had no medical issues as I didn’t want to risk going into a hospital in one of those countries, lol. The doc in discussing my results said everything was fine, but that I had high cholesterol. I was 22 at the time. I don’t remember if he mentioned any numbers. Anyhow, subsequently throughout the years, my cholesterol was always flagged as high, with LDL between 160-200. Also, my HDL was always very high, 80-110.

This frequently worried me, and I tried to diet and exercise it away without success. Since the mid 90’s, I’ve been been on CR (as a result of reading Walford’s CR promoting book, lol), to various degrees, these days pretty mild CR, maybe 10% at most. Cut out saturated fat as much as I could, avoid meat except salmon once a week, tons of fiber, fruit, nuts, seeds etc., whole nine yards, exercise, lift weights… all useless as far as cholesterol. In the last few years, pre-diabetic, BP creeping up. Exercise actually always raises my blood sugar substantially. Just useless, so I’ll be looking to drugs next.

I don’t know why my body is like that. On the flip side, I was always reasonably slim, BMI never above 21 or so. And other than my terrible current numbers, healthy - I did develop mild IBS in my late 20’s, that resolved when I drastically upped my fiber intake. Also, my BP was always around 110-115/65-75 or so until 4-5 years ago, so age about 61-62 where it went as high as 140/90, currently 125/85 or so. My hsCRP was always lowish, 0.3-0.5, except last year 0.6. One interesting point, people frequently mention that I look young for my age, guess wrong by 15-20 years fwiw, don’t know if it means much healthwise. I do feel young, but then again, everyone does … other people my age, and often in their 40’s seem to me mentally old, not just physically - but this might just be arrogance speaking, subjective BS.

Never smoked, didn’t drink to excess, no street drugs.

[ng0rge]

@CronosTempi

I was 22 at the time. I don’t remember if he mentioned any numbers. Anyhow, subsequently throughout the years, my cholesterol was always flagged as high, with LDL between 160-200. Also, my HDL was always very high, 80-110.

Very interesting, thanks! Just curious if you have any triglyceride numbers, only because of the possible connection to Lean Mass Hyper-Responders. But it doesn’t sound like your diet was particularly low carb or Keto ( can be Keto with low saturated and high unsaturated fat) and it’s unlikely your blood sugar would go up on that diet.
Low inflammation (HsCRP) is certainly good and follows with no plaque. Inflammation, in relation to CVD, is usually irritation of the endothelium/intima of the arterial wall and often caused by high blood glucose. My theory is that you can have slightly higher ApoB, and as long as the endothelium/intima stays healthy and non-inflamed, plaque won’t start.

[CronosTempi]

My trigs were always lowish 50-70… until last year, suddenly 103. I’m not keto.

I really don’t know why my CAC score was zero. I was so convinced that I had massively calcified arteries because of my terrible lifelong lipids, that I joked with the techs who were administering the test, that they should’t worry when they find out my calcium score, because I already ordered an Uber ride to the cemetary, they can just shove my body directly from the machine into the Uber car.

When I got the zero score results a couple days later, I was angry, because I thought they mixed up my records with some other patient. I simply couldn’t believe it and wanted to immediately retest, but my doctor talked me down. It wasn’t some fly by night testing place, but UCLA, and I paid $250 as my dumb insurance never wants to cover anything unless I’m actually dying (maybe my autopsy? Nah, surely not), zero prevention.

As to theories… eh, I think it’s all a genetic crapshoot, as I always say, it’s better to be lucky than good. What accounts for these freaks, like the recent 110 year old fellow in apparently good health, who has contempt for exercise, terrible diet and was a heavy smoker for 20 years? There is no explanation, just luck. Then you have my lifelong nonsmoking vegetarian former coworker, who exercised, was slim and health conscious, died from lung cancer at 55. Blind luck.

That said, on a population level, endothelium might be key, low blood pressure so the ApoB particles are not being pressed into the walls, decent BG so wall is not being damaged, decent antioxidant levels so wall repair happens fast. Probably those are some kind of factors, but not decisive. Currently we simply don’t know. I keep thinking about that Peter Attia interview with a Dutch cardiologist researcher who mentioned how there are rare cases of FHC folks who live a normal lifespan despite truly epic levels of LDL. Something protects them. Would be worthwhile to find out what.

[adssx]

@Virilius

a) increase apoA (not just HDL-C)

Obicetrapib increases Apo A1 by 48%: https://www.sciencedirect.com/science/article/pii/S0002870324001169?via%3Dihub

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@Virilius

b) strongly decrease inflammation markers (something statins and ezetimibe already do, just better)

Which inflammation markers? hsCRP? IL-6? Others? What’s the best drug to reduce each of these?

[John_Hemming]

There is an interesting question as to whether anyone on this forum also has an CRP below 0.15mg/L.

I would argue that citrate (which is not really a drug) is a good molecule for reducing baseline CRP.