Cardiovascular Health

#1080

Low is good, but if there is a level below which there is no further plaque buildup or accumulation, then reaching that level should at least keep you from further deterioration, no? At least as far as atherosclerosis is concerned.

Of course if you want plaque regression, then you may need to hammer down with statins to the bare bottom.

But what of a case like mine, where I’ve had a life long very high LDL, HDL, TC, ApoB and very high Lp(a), and was unmedicated until I got on 10mg/day atorvastatin five years ago, but at age 65, had a CAC score of zero? Of course maybe I have soft plaque, but assuming someone doesn’t, then for such an individual getting to a level below LDL of 70 or so, presumably where no plaque will build, is there a point to going below that? FWIW, that is my plan, in addition to the atorvastatin I intend to add 180mg/day bempedoic acid and 10mg/day ezetimibe that will hopefully push my LDL from the current 133 to below 70 (I’d love a PCSK9i, but can’t afford it out of pocket).

Of course, there may be other benefits to lowering the LDL/ApoB levels, than plaque and vascular health (including cancer!), so, pushing far below plaque accumulation may make sense for other reasons.

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#1081

Your cumulative lifetime exposure would be pretty high at 60, but at least you avoided that it progressed further unchecked. To give a number to your excess lifetime risk you should have an idea of the values from birth to present day.

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#1082

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#1083

The argument that you have very high cholesterol and a CAC score of 0, so why do anything seems a lot like those who say they’re lifelong smokers and don’t have cancer.

It seems akin to playing Russian roulette. I prefer to take that last bullet out of the gun just to be on the safe side.

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#1084

To be clear, that’s not my argument. As I said, I Intend to drive my LDL below 70 at the least, and more if I could.

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#1085

You might want to take a look at the Danish study that I posted where the median age was 58. In the group with high LDL-C and zero CAC, I would say that 50 years is a long time to be winning at Russian roulette. It would suggest to me that there is a scientific explanation that hasn’t been clearly defined yet, not just “luck”.

Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL…

https://www.rapamycin.news/t/the-ldl-kingpin-theory-one-ring-to-rule-them-all-lmhr/15982/6?u=ng0rge

#1086

there seems to be a compounding exponential type risk of heart disease and stroke with Apo B exposure. so 50 or 58 years may hardly tell us anything about what is needed to avoid risk in our 90s, 100s and hopefully beyond

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#1087

That may be, but it’s certainly enough to arouse my curiosity. 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?

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#1088

@ng0rge

Interesting to study - yes

We as totality of data driven health optimizers and longevity seekers should take gambles based on that - does not seem smart

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#1089

Of course not, my interest here is not to drive recommendations or public policy but merely scientific curiosity at this point. However, I think that the scientific community is also starting to take a look at this (see my post from the Journal of Clinical Lipidology) and a better understanding as well as possible new therapies may come out of it.

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#1090

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

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#1091

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.

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#1092

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

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#1093

@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.

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#1094

@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.
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#1095

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

This paper sums up the “mainstream” view:

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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?

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#1096

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

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#1097

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!

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#1098

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

#1099

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.