Cardiovascular Health

#1504

LDL: The lower the better

LDL particles are the prime factor behind the buildup of fatty plaque in arteries that can rupture, triggering a heart attack or stroke. “We have a paradigm in cardiology that the lower the better,” says Erica Spatz, a cardiologist at Yale School of Medicine in New Haven, Connecticut. “The question has always been, is there a bottom?” The query has taken on added significance as more powerful treatments are widely prescribed and even stronger ones are in the pipeline, including advanced biologic therapies and gene editing.

Based on a huge body of evidence, people at risk of cardiovascular disease who are prescribed cholesterol-lowering drugs, including high intensity therapies, can feel assured it is a sound strategy, says Donald Lloyd-Jones, a cardiologist at Northwestern University. Lloyd-Jones was a member of the American Heart Association (AHA) committee that released the latest guidelines on cholesterol therapy in 2018 (an update is expected in 2026), as well as the group’s past president.

“We haven’t found a level that’s ‘too low’ yet,” he say. “I like low. Low is what we’re trying to achieve here.”

PCSK9 inhibitor drugs turbocharge the liver’s ability to break down and eliminate LDL. “With those medicines we can get to very low LDL cholesterol levels, below 30 and even below 20 mg/dL,” Spatz says.

A study of evolocumab, a monoclonal antibody that targets PCSK9, found that when people with cardiovascular disease added the drug to their statin regimen, their LDL dropped by 59 percent after two years and their risk of heart attack, stroke, or cardiovascular death fell by 20 percent.

Last year, researchers argued in an editorial in the journal Circulation that LDL levels in newborn babies generally range from 20 to 40 mg/dL, “suggesting that higher levels seen in adults are not essential for cellular processes.” And some adults are born with genes that keep cholesterol levels in the basement throughout their life, with no adverse consequences and healthier hearts, they noted.

Read the full story: Can your cholesterol drop too low? - Drugs can now drive blood cholesterol levels lower than ever. But how low is too low? (National Geographic)

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#1505

Why are we using association studies in 2024?

A rant on the topic:

There has been over 80 years of research on cardiovascular disease, before that infectious disease was much more important to tackle.

At the start that was important, which the Framingham Heart study in the 1950’s showed that total cholesterol was significantly associated with heart disease, funding started because of a president getting a stroke. Along that researchers found in the study associations for obesity, smoking, high blood pressure, (Lipoproteins like LDL and HDL was just starting to get measured with expensive centrifuges). Mechanistically cholesterol was also found in plaque and rabbits fed cholesterol developed disease (mice did not, but they apparently don’t have any LDL).

So by 1950’s we know mechanistic reason (cholesterol in plaque, feeding rabbits), and association (Framingham Heart study), a few decades later they found people with FH and higher total cholesterol developed disease much quicker – in their 30’s getting the first heart attack, and for those with more deleterious variants with TC up to 1000 mg/dl – in their teens.

So by the 1970’s we had mechanistic, association, and genetic studies. Race was on to develop drugs to lower cholesterol. Many weren’t that effective and then eventually statins were developed to inhibit HMGCR which would really slow down cholesterol synthesis which they found out it was a slow step in the synthesis of cholesterol. Massive blockbuster drugs, except the moronic skeptics with unpersuasive arguments for the intelligent started publishing books in the 80’s trying to refute the cholesterol hypothesis, which dampened statin sales.

Eventually large clinical trials were done showing that using statins PREVENTED heart disease – stroke, heart attacks, and as such, even lowered mortality (4S study). Which shouldn’t have been so unsurprising, but before that drugs had more side effects.

So we have mechanistic, association, genetic, and clinical trial evidence of one of the few PREVENTION drugs and strategies, this is medicine at its finest. Then the genomic revolution happens and we have so many genes to find even more genetic evidence and over longer periods, that strengthens the causality even further and shows the compounding effects of lowering early for preventing cardiovascular disease.

The LDL cholesterol deniers are literally the dumbest people in the world. There has been so much research, effort, evidence, markets and insurance signaling, that LDL cholesterol matters, by a lot. I have to say, people don’t have to do anything, just eat popcorn, I will and witness and know that these people are absolute fools. :tada: :popcorn: :popcorn:

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#1506

We may put it more diplomatically. They are not fools, although they tend to be stubborn, for many reasons not excluding personal likes and dislikes in diet. They tend to like anti-estabilishment affirmatiosn, they tend to dislike strongly scientific research, for various reasons. they also tend to cling to whatsoever rational (or apparently rational) arguments that tend to deny the preponderance of evidence (like, the part of the population which will not die notwithstanding their excess lipids).
At the end, perhaps the above is a foolish attitude. Certainly reckless.

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#1507

There is a middle ground between the
Ldl deniers and lower the better.
The RCt evidence doesn’t support targeting below 50 apob with pharmaceutical interventions for primary prevention.
The mendelian randomization evidence is inevitably ltd.
Which leaves Target 50 as a sensible, evidence based approach.

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#1508

In the current year, the pyramide of evidence has been inverted.

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#1509

Just adding this post, copied from here: Blood Circulation: The Overlooked Fountain of Youth - #30 by RapAdmin

You do know that the number one symptom that people with serious atherosclerosis first experience is heart attack and death, don’t you?

See the peter attia podcast on atherosclerosis - see this video, queued up to the exact point of the relevant discussion:

Screen Shot 2024-12-23 at 3.24.38 PM

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#1510

Yeah, I started the process of getting the Cleerly done instead of the CAC this year. It will take another couple days to get the details I guess. I was doing it with email because I’ve been busy during these short days. They want $1300 to do the interpretation and virtual consultation. She never said what it costs for the scan. I think the scan is out of pocket, maybe the consultation is covered. That’s what I’m trying to figure out. I asked all these questions with the email and instead of answering I got a prewritten thing. I’ll peck away for awhile then maybe call if it doesn’t work. Christmas is probably a bad time.

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#1511

Please let us know the details once you find them out - this is something many of us are likely interested in.

#1512

Yes, they use an inverted evidence hierarchy pyramid.

I was surprised to hear that the Mossad did extensive testing when planning for their Pager attack as highly competent organizations and individuals (no matter what you think of them) I would expect could just figure things out without experimentation and testing.

But it seems you can’t really get past experimentation and testing, which is at the top of the evidence hierarchy.

Of course some people choose to dismiss this, and invert the evidence hiearchy, but it’s their own health and they’re running it like the most slouchy project known to man. And NO, mechanistic studies are NOT testing or experiments.

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#1513

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#1514

These papers suggest that there is more nuance to LDL

It seems metabolic health correlates better with CAC scores
https://www.internationaljournalofcardiology.com/article/S0167-5273(24)01320-2/fulltext

Some athletic people have very high levels of LDL yet zero CAC

In both papers lower TG and higher large HDL were more predictive of better CAC scores

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#1515

Nick’s own case report of him being 26 year old with a CAC = 0 doesn’t matter even if his LDL-c has been elevated for 2 years, that’s because 90% don’t have a CAC >= 1 below age 30 anyway.

ApoB measures both the VLDL’s particles that carry TG’s and LDL’s that carry cholesterol, and it’s the total amount of apoB particles that matter the most, since it’s the rate limiting step of ASCVD.

See this thread I made: Apolipoprotein B (ApoB)

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#1516

The article is very interesting but…It is not a trial, it’s just a n=1 case history.
For all I know, it might even have been cherry-picked. There is an ongoing study on LMHRs, with a small coort of this group. They might have chosen this individual to make a case against the hypothesis of ApoB.
It would not be a strong case anyway, since we all know that it takes time, 10 to 30 years to develop full-fledged atherosclerosis and the rule may be valid even in the case of extremely high LDL.

But the individual under study had no soft plaque either, so the case does prove that an extremely high LDL (450 m/dL average) does not cause coronary plaque accumulation after a short time (2 years) in at least a very small part of the population of LMHRs.
In other words, I’m pretty confident they cherry-picked the individual with no plaque to make a point. There might be no other individuals with zero plaque in that cohort. We simply don’t know. Skepticism must be kept high because the keto guys are often religious in their zeal and religion is sometimes (but not always) the worst enemy of science.
The time is too short, even if the LDL is high, time might be a governing factor even in the presence of high cumulative values of LDL.

Again, I am curious but we should be waiting for articles with even a simple statistical analysis of the full group (which is a small one), after at least 10 years. It may result that these lean individuals enjoy some metabolic protection from atherosclerosis, but so far it all remains very hypothetical.

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#1517

There are studies showing that indeed, even though you are metabolically healthy with no other risk factors, higher LDL is associated with more disease.

I don’t understand how magically metabolic health would make you protected against disease if apoB causes disease independent of anything else in a normal population. It’s a leap of faith without evidence.

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#1518

Both poor metabolic health and high LDL levels are bad for your heart and can cause heart issues. It’s doubly worse if you have both.

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#1519

You can’t have a heart problem if your LDL or apoB is low enough and early enough, even if you are diabetic.

#1520

Yes you can. My mother’s LDL was low but her triglycerides and HBA1C were through the roof. She had a heart attack and stroke. Unfortunately we never measured her ApoB.

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#1521

LDL is falsely suppressed at high triglycerides so it wasn’t accurate. Besides, even if it was it is the lifetime exposure that matters, unless you know it was truly low for a long time.

#1522

I’m relieved (thrilled really) to find a local cardiologist/lipidologist well versed in research/protocols of Sniderman and Dayspring. My LDL is high and evidence of atherosclerosis is present although age-related risk factor is very low. He has me starting on 5mg Crestor. Follow-up testing in 6wks.

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#1523

Centenarians frequently display improved [i] glucose management and insulin signaling, as well as [ii] a more favorable plasma lipid and lipoprotein profile. They also show fewer overall signs of oxidative stress compared to aged controls [173, 174]. While a significant proportion of centenarians with diabetes also have hypertension, they tend to experience fewer diabetes-related complications, such as lower prevalence rates of peripheral arterial disease, neuropathy, and congestive heart failure [175]. Additionally, this population maintains relatively high cognitive function and physical fitness and is highly resistant to diseases, such as stroke, metabolic syndrome, and CVDs. This suggests that various factors may play a role in preventing or mitigating these adverse outcomes among centenarians. Here, it seems that the combination of a reduced production of pro-inflammatory cytokines regulated by polymorphisms in specific genes and an increase in antioxidants has a positive effect on their health status. The delay in age-induced vascular impairments observed in centenarians has been linked to improved lifestyle conditions, with healthy dietary patterns and regular physical activity. Given that dietary patterns profoundly influence the composition of gut microbiota, it can be postulated that these changes may also, at least in part, help attenuate low-grade inflammation, thereby reducing the subsequent risk of CVDs.

Centenarians—the way to healthy vascular ageing and longevity: a review from VascAgeNet

Open Access Paper:

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