No Lower Limit? Strikingly Low LDL-C Levels Boost Cardiovascular Protection With No Added Safety Risk

#83

I would just say your trust in testing seems absolute and that doesn’t seem based on data. More that I read about that MRI is just volumetric measurements unless I am missing something. Not that it automatically correlates but I wouldn’t want to only react after losing hippocampal volume. I would rather preserve volume.

That being said, I engaged because I was curious at your rational and the data behind it. If I thought you were just nuts, I wouldn’t have replied.

I had my own decision with elevated LDL in isolation. I chose eventually to treat and mostly I feel like my decision has been validated as more data comes out. This was both before my father’s diagnosis as well as the recommendations regarding LDL and dementia.

Curious if you know your apoe status and LpA number? My LpA is very low as is things like hsCRP, insulin etc. But my homocysteine is not as favorable. Do you hold your imaging above these markers in predictive value?

Imaging lies. Curious why you trust it so much? Like occupation?

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#84

Yes, the Neuroquant MRI provides a variety of volumetric measurements, which are useful. However, it also examines the integrity of the blood brain barrier, looks for white matter on the BBB, and other tests. I consider these results at least as important as the volume/atrophy testing.

Per your other questions, I do not have an APOE4 allele, my LDL-P is 1113 and trending down over the years with no treatment, LDL-C is 104 and trending down significantly over the years (used to be up around 160-180) with no treatment causing the change, and my triglyceride to HDL ratio is .96 (used to be lower)… My LP(a) measures less than <7. Homocycsteine is 11.5 and hsCRP didn’t used to even register, but most recently came in at .67 (still low). My HOMA-IR bounces between .5 and .8., my resting heart rate is low 40s and my VO2 max is 43. Blood pressure is excellent.

In a nutshell, my numbers are generally very strong, but my LDL has always been elevated (but decreasing on its own) and my particle size for both LDL and HDL isn’t great. Most doctors immediately recommend statins for me, which is why I had to learn about this stuff.

The problem is my numbers have always been strange by large population standards. Some numbers come in off-the-charts good, and others are not good at all. I’ve never aligned with large population standards.

I keep finding over and over again where general data standards don’t apply to my situation, and I believe the same is true for many members of this forum, which is why I shared the alternative viewpoint to test first and only treat if a problem exists. Enough members of this forum do not fit normative standards that this is an important consideration in discussions.

For example, there’s another thread on this forum where I shared the incongruity between my A1c numbers being pre-diabetic and my HOMA-IR bouncing between .5-.8. (crazy good). It took many years before the science caught up to acknowledge that the A1c number ranges derived from large populations have little applicability to endurance athletes because of longer red blood cell retention/lifespan resulting in higher glycation results than for normal populations with the same insulin resistance.

I believe the same is true with CVD. We know enough to know the answer isn’t simple. But it will be a long time before all the comorbidities can get unraveled into an actionable, safe solution. Until that day, taking massive action to artificially lower LDL introduces unknown risks to the entire system that could be larger than anyone understands.

And yes, Cronos Tempi, I understand what the data shows. I’m just saying that more is unknown than known. Forcing LDL to sub-biologic levels through intensive meds violates everything I understand about systemic behavior. It smells bad. Really bad. Something is missing from the analysis, and I’m confident that when it surfaces, it won’t look good for that protocol.

Hope that helps.

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#85

I agree with this but have a real question, what is the actual biological level for LDL-c?

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#86

The Framingham cohort, among others has been studied for decades. To say that it’s in it’s infancy is ridiculous.

The Swedish and British health data banks are huge and have been used in lipid studies for decades. Especially relevant, is the Swedish twin studies.

The problem with your test first policy before prescribing statins, is that it is reactionary, not preventative. It hard to reverse the damage done by the time you detect a clear signal.

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#87

Just because studies have existed for decades does not translate to a mature knowledge of the topic. Time of study and depth of knowledge are not equated. IMHO, the science behind cardiovascular disease is in its infancy because the complexity of all the comorbidities confounds the conventional research process. They’ve found many correlations, but they aren’t even close to separating out the cause-and-effect relationships into a depth understanding that accounts for all the outliers in the data.

And I disagree with your conclusion regarding “test first” policy. The onset of symptoms is progressive over many, many years. One can see progression from current “zero” status to clear signal long before any meaningful damage. Your logic doesn’t hold.

My personal preference is the known, controllable risk of time and monitoring versus the unknowable, possibly large risk of loading up on statins and related treatments to artificially lower lipids. If the system is currently not producing any symptoms of CVD then there is nothing to treat.

The rule of medicine is to first do no harm for good reason. Adding a pile of meds when nothing is wrong is trading a known, controllable, low risk for an unknowable risk.

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#88

Since we agreed to disagree, this really is no longer a back and forth. Whatever I write here, is more in the spirit of explanation of my framing which doesn’t necessitate a formal response. It’s here, for you to contemplate or not - no big deal.

See, to me this is far more transparent and actionable. I frequently refer to how I see medical science and practice as operating on a black box model. There is inputs - for example driving LDL/ApoB very low with statins - that goes into a black box, i.e. the body deals with it somehow - and then there is output, which is the clinical outcome. I don’t need to speculate what happens inside the black box - it’s opaque, as you say, there is a ton we don’t understand, so our speculation as to what occurs inside might be wrong at any given time. But what is completely known is (1) what is the input: statins (or LLT in general) driving LDL/ApoB very low and (2) what is the outcome of such: MACE becomes vanishingly rare.

And that’s what I mentioned before - the power of outcomes. I don’t have to know what happens inside, what the mechanism is. All I have to know is the outcome - if I employ LLT to drive ApoB very low, MACE becomes virtually extinct. Done and dusted.

Meanwhile, you are worrying about what happens inside the black box and how little we know and what the long term consequences might be. This, I submit is 100% unnecessary at some point. Once we have enough of a clinical track record your theoretical worries by definition become resolved and irrelevant. If we have at this point decades of experience with statins, and a track record that proves they lower not just CVD but ACM apart from CVD, your patients live longer with statins than without, even if statins are not indicated going lower still improves odds and prolongs lifespan/healthspan… then saying “one day we’ll discover what a terrible mistake statins were” is falsified completely - the mythical “one day” you worry about has already come and gone and we have the outcomes. And given how many people were on statins - FOR SURE THERE WAS A GOOD NUMBER of folks like you and me (discordant lipids - high ApoB no plaque in the 60’s). And still no MACE. Statins will not suddenly change their outcomes as we learn more about lipids and how they work - we already have the life long records. Done. That’s the power of outcomes. Nothing will suddenly “smell bad” - the outcomes will not suddenly change. That may have been a justified fear when we just started out with statins and didn’t know long term impacts - but it’s been decades and now the time for the bad smell has long gone. And I’ve got news for you we don’t really know how most drugs work. They just work, and that’s good enough if the clinical records are long enough. So my decision tree is very simple:

I don’t have to worry about unknown mechanisms which will one day blow up in my face. I have long term outcomes, inclusive of the dreaded side effects or unknown effects of statins and these outcomes scream: taking statins gives me a shot at the same outcome with high probability. Meanwhile abstaining from it means “doing nothing” represents the very gamble you fear - you have no idea what the long term impact of doing nothing might be. I have a high degree of confidence (based on long term outcomes) - you have a high degree of uncertainty centered around your very fears of too little knowledge!

Incidentally, what is a sub-biologic level of LDL? What is the “natural” level of LDL? Young people have very low levels and the younger the lower - when they are furthest away from death and decrepitude. Maybe we should aim for that? Just as with blood pressure? And other biomarkers? But I tell you what - again, it’s irrelevant. Let us even assume that there is a “sub-biologic” level of LDL (I don’t believe that - it’s an arbitrary level). We already have long records of outcomes… and nothing bad has happened - the opposite.

But OK - let’s talk principle. Again, I think your conception of “elegant biology” is coming through and clashing with my “horribly designed machine” model. You think: “there’s a ‘natural’ biological level of LDL and going below is going below ‘spec’ of the design and trouble will come”. I think not at all that - I think "here is another shitty body adaptation or sloppy design that has outlived its usefulness and in the current environment is actively disruptive, we need to fight it HARD by going outside of the sloppy design spec. Think of sicle cell disease - an adaptation against endemic malaria, which was useful once upon a time, but in a time of good anti-malarial drugs or vaxx, it is now all downside with no upside… outlived its usefulness and was a rotten solution to begin with (sickle cell is terrible in general).

I think it’s exactly the same with LDL levels. There are all sorts of theories how high serum ApoB developed, but there is in general some thought that many thousands of years ago, high ApoB was helpful if food was very scarce and there was starvation. And the worst - Lp(a) (which you would claim should not be eliminated since it exists as part of an ‘elegant design’ must be somehow useful and we should not screw with it). Well, the theories behind Lp(a) is that it was useful if you had little access to vitamin C rich sources - perhaps in winter with a snow covered ground. It also was very good at patching up leaky vessels from injuries. So back in the day when we walked in the snow (no vegetation with vit. C - Lp(a) to the rescue) and mostly had access to big game that frequently injured us (Lp(a) to the rescue), and then we might get infected from wounds (high LDL to the rescue) and then ran out of all food (high LDL to the rescue). Useful. But at a cost - CVD in older age… which was irrelevant to evolution since by then you already reproduced, so nature didn’t care - it needed to rescue you NOW so you could spawn, and what happens later doesn’t matter, as old postreproductive age renders you irrelevant. And then we come to the modern age where we don’t fight off cave bears, don’t get injured on the regular, have access to plenty of food rich in vitamin C, are not starving and have access to antibiotics. It’s design that has outlived its usefulness. Today it’s a shitty design that affords us CVD - and we need to go outside of “spec” to fight it - crush Lp(a) and ApoB if we want an "unnaturally longer and healthier life.

And so on. We must FIX the flaws of our terrible design, not mistake it for an “elegant design” and cling to lethal design mistakes. We must modify - not do nothing.

It’s the classic naturalistic fallacy. “Natural” is the state of life that was “nasty, brutish and short”, not something to aspire to, not something to preserve in pristine condition when it’s utterly destructive here and now, and only useful - at a horrible price - in the jungle/caves/steppes.

This post is getting too long and I still have more to say (about decision making trees and game theory as it applies to medicine) so for now I’ll shut up, perhaps post again some other time.

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#89

You’ve already raised most of the points previously that you’re repeating in your post above. I get that they are important to you, but we already agreed to disagree.

I’ve stated my position clearly. There’s nothing more to add.

I spent my career in advanced risk management modeling. We interpret the same data differently and come to differing conclusions regarding smart risk management.

We are both committed to our viewpoints with total integrity by betting our health in alignment with those views.

I wanted to share my view because it contradicts the general tone of this thread. I felt it should be added in case it helps others. People are welcome to disregard that view if they don’t find it useful.

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#90

Interestingly, we are very close chemically with my numbers being very close to yours in most categories. Except my LDL was 140s and no diet - including vegan for 3 months could get it lower. And it was rising slowly with age.

At 100ish and your other numbers and tests, your decision is very reasonable. I certainly would have agreed 5 years ago but would probably have changed my mind today.

I have the same low 40s HR and pre diabetic a1c (at times) with low HOMA-IR. I don’t believe it is all because of long lived red cells. My fasting sugar is just relatively high with an insulin of 3.3. HOMA-IR, while very good for insulin resistance, doesn’t tell the whole story. For some reason, my body wants a highish fasting despite excellent sensitivity. If I ran a 2hr marathon, sure, long lived red cells.

Thank you for your occupation. I am a strong believer in how much that guides decision making as we get older and established in our careers. Medical specialists and generalist are an easy cohort to observe this. There is a similar foundation but then vastly different priorities and thought processes. We are not nearly as flexible as someone in their 20s.

I would agree with Cronos about the elegant system theory. Our system was developed in a vastly different environment with food scarcity and trauma being much greater risks. The goal of preventive medicine is adapting that system to one of excess calories and minimal trauma.

And the system has only 1 goal and that is reproduction. Survival after that is less valuable (but there is the grandmother hypothesis). When you look at life through this lens, sex hormones are over emphasized relative to longevity. And you start realizing that there is very little to the system that is actually designed to have us live a robust life into our 80s. It is hard to reconcile the inputs with our rather robust lifespan. There is a lot of over engineering to accommodate for incredibly diverse climates but that doesn’t mean there is any value to life after 50 or so. It is just that the over engineering tends to get us more years but the system isn’t good at that because it was never the intent or focus.

I don’t believe without new evidence that an MRI can reliably determine the health of the BBB. I don’t doubt that someone claims it does. MRIs can’t reliably diagnose appendicitis or a common bile duct stone despite the radiologists thinking they can - and even publishing data that they can. So my world view is to be extremely skeptical of anything a radiologist claims. And I admit I am probably too skeptical. Radiologists have a training that doesn’t really have them seeing patients. All the answers are from a picture on a screen and they put too much faith in pixels.

I don’t think these things have to be about agree or disagree. Everyone has a different perspective. My perspective is that people often fear side effects from medications irrationally. Sometimes it is a big pharma mistrust. Or mistrust of doctors or science. I see it all the time in patients and friends. Medications are admitting that we are fallible and that goes against our egos. None of this may apply to you but it is very common. I promise the excess deaths from this attitude vastly outnumber the ones from medication side effects.

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#91

I’ve toured the literature and see the BBB studies. Not Neuroquant but Dynamic Contrast Enhanced (DCE). Lots of pilot and feasibility studies. I didn’t see anything with predictive value over time.

Like any pathologic change with dementia, once you have them it is probably too late. So I would put a malfunctioning BBB in the same category as loss of hippocampal volume - once you have those things, you are doomed.

At least at the current levels of detection and the data on what those levels mean. I imagine at some point, we maybe able to detect changes so early that you could tailor treatment.

If I had a normal Neuroquant and DCE, it may be helpful for long term financial decisions but not anything medical at this point. In my opinion obviously.

Google Gemini suggests that no one is getting DCE outside of research protocols. The RSNA guidelines say research only. There is so much MRI scanner variability in the community for these very subtle findings - so research only on dedicated scanners.

So curious Todd - did you get a DCE outside of a research setting?

Neuroquant is available everywhere by independent radiology groups. It is really just a regular MRI with software to do the volumetric analysis. Very different animal.

#92

I appreciate the contrary viewpoint. It’s good to have a diversity of well informed perspectives and respectful disagreement
Thanks for posting.

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#93

No matter how strong the evidence to the contrary, there
are still those who believe the earth is flat.

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#94

Relevant to antagonistic pleiotropy. New paper.

Genetic trade-offs in fertility and longevity explain the maintenance of disease-associated alleles in humans

https://www.nature.com/articles/s41559-026-03140-z

“Genetic variants that increase the risk for complex diseases persist in human populations, despite adverse effects on health and longevity. Life-history theory predicts that such alleles can be maintained by trade-offs arising from pleiotropy, yet direct genomic evidence has been limited. We asked whether disease-associated variants persist because they enhance reproduction, despite costs to health and lifespan. By analysing genome-wide data across 62 diseases, longevity and fertility, we show that disease-risk alleles are, on average, associated with reduced longevity and increased fertility. Moreover, the subset of alleles that increase both fertility and disease risk appear to have been favoured by natural selection over the past 50,000 years. Using Mendelian randomization, we detect a causal effect of genetic liability to disease on longevity, but no robust evidence for a causal effect on fertility; importantly, these estimates remain stable after adjusting for socioeconomic factors. At the individual level, we compared offspring numbers between affected and unaffected individuals with high polygenic disease risk. For most diseases, affected individuals had more children than unaffected ones. But for early-onset diseases, the pattern reverses, indicating reproductive costs of early morbidity. Together, these results support antagonistic pleiotropy and help explain the persistence of disease-risk alleles in human populations.”

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#95

“Flat earth??” Seriously? I’m assuming your statement was in reference to my input given the placement in the thread. Wow!

You are either misunderstanding my position, or just choosing to be unnecessarily insulting to that position with an inappropriate personal attack.

The only thing I advocated was for people to test for any evidence of cardiovascular disease before treating for cardiovascular disease (and prevention). I’m challenging the idea of just slamming your LDL as “preventative” when there’s literally nothing to prevent as proven by testing. Well-informed doctors who strongly advocate for statin use (some in this community) fully support that position as well.

I understand the “preventative” reasoning based on large population studies, but the nuance is that preventative value may have no applicability to an individual with no predisposition to CVD.

Adding medications when there’s no evidence of a problem to treat may actually increase risk and must be weighed carefully.

I also state in this thread that I fully support lipid treatment protocols if the individual shows evidence of CVD progression.

For you to equate these comments to “flat earth” seems a bit off target (at best), and an inappropriate personal attack as well. Bummer.

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#96

But you can’t test, wait for disease, and then prevent - that doesn’t work as well as just preventing.

The concept of prevention is to prevent something but you advocate for waiting for evidence of disease before taking steps to prevent. You realize this concept results in needless disease, don’t you?

The serious side effects of Statins are well known and documented. The latest number I could easily find from 2019 is 818 million prescriptions. What sort of “unknown” risks are you talking about? Do you not agree that Statins are one of the best studied medications of all time?

Your stance flies in the face of pure numbers. Anti-statin zealotry is a real thing and just because your argument is a bit better than some, doesn’t mean it is logical given the science.

Your Neuroquant MRI doesn’t look at BBB, it looks at downstream damage from a broken BBB. If you have downstream damage, it is too late.

You might live to a 100 with high LDL and never have a plaque at all. But take 1000 people like you and only treat after they show disease and more people will die of CVD and AD than if they took statins.

Real question - what sort of risk of statins are you worried about?

You realize that the latest recommendations involve testing LDL around age 9?

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#97

Is there serial CCTA data over an entire ASCVD career?

I wouldn’t be surprised if once you have plaque or something the changes become hyperbolic, like a threshold, and no matter how much medications you take it won’t have the same effect as if you started earlier. It’s called advanced disease for a reason, that’s what Allan Sniderman who’ve researched lipids for 50 yrs have called positive calcium scan scores.

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#98

IMO both sides of the LDL-c debate have gone a bit into the extreme and clearly there’s plenty out there to argue either way/case. Scientific studies usually point to lower the better, whereas anecdotal/practical views are usually the opposite.

IMO, bottom line is that low/normal LDL-c is better/safer than high, and usually with low LDL-c you’d also heave low APO-B as they kind of go in tandem. Having said that not all people with high LDL-c will die of heart disease. My father’s LDL-c was never less than 150, and while he did have angina/CVD later in life around 70 he lived fine with it for over 15 years without taking any lipid lowering drugs, but he did cut animal fat and used mainly Olive oil for cooking. Had couple aunts with mid 100’s also and they lived to 93 and a 100, no sign of CVD. But that doesn’t mean everyone will have same luck. My circle of friends in same generation as me (not family) I know at least 5-6 people who have died young (45-60) of heart attacks.

From everything I’ve read and researched and then injecting a decent dose of common sense into it, I’ve come to the conclusion that I do not need LDL-c in the 30’s as an example, but I’ll definitely attack it till I see it between 60-70. For a healthy heart, apparently there’s other factors that need monitoring also, such as A1C and hsCRP. Plus, as everyone knows exercising is probably one of the best things you can do for heart health (as well as health in general).

Everyone can make their own mind, I guess, but the prudent thing to do IMO (especially if you’re past 40) is to try and keep LDL-C at low normal range.

I also agree with the notion that we should not wait till we see sings of CVD. I’d rather cautiously take certain lipid lowering drugs and diabetes meds for preventative purposes and I’m actually doing that (as I’m sure many in these boards are) and intend to continue.

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#99

Probably not, because solving one bottleneck reveals the next.

Imagine a hypothetical population that all gets cancer at 80, but die of CVD first at 79. You cure just CVD, but only get a year extra. You cure just cancer and would see nothing. But if you cure both, you might see much longer life.

This shows up in lots of long tail problems. In longevity there’s a similar concept of a “wall of death”. If everyone dies at 80, there’s no evolutionary pressure to prevent things that would kill you at 90, so we may encounter a build up of problems we need to solve, and we need to solve all of them before we see a significant jump.

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#100

This sort of discussion is what makes this forum valuable. The key to getting the most value out of it is to maintain an open mind while having the courage to act when you believe you have enough information. I try mightily to avoid “deciding what is true”. No one has to convince anyone of anything here. Add value by sharing your research and analysis. I’ll make my own decisions. The root of all evil is over confidence. Thanks for the contributions.

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#101

The problem with this discussion is that it superficially appears to be about statins. It’s not. Statins are merely the high-attachment drug featured in this discussion. This is really about research interpretation and risk management philosophy.

I’m not anti-statin. I’ve already stated that if there are any signs of CVD (or familial history) then statins make sense. I’m absolutely not “flat earth” as other members might disparagingly oversimplify. Statins are well proven and can deliver high value in the right circumstance, as both you and Chronos correctly point out.

No disagreement.

The complication driving this discussion is coming from other areas, but is mistaken as pro/anti statins:

  1. Prevention Strategies: Some people believe statins should be pro-actively consumed as a preventative measure against a high probability that CVD (or related dementia) will likely strike based on large population studies. There are two potential problems with this logic - the applicability of large population studies to any individual (because each decision to ingest statins is individual), and the wisest preventative strategy for that individual from a risk/reward standpoint when all factors are considered?

1A: Large population studies can provide great value in terms of correlations and tendencies. However, one must always be careful applying those results to any individual. Yes, statins are well proven and deeply researched; yet, more remains unknown than known about CVD (and dementia). The problem is CVD is a co-morbidity issue with complex systemic inter-dependencies that science has not fully untangled, which is why N=1 is so incredibly important. The outliers in the data are legion. This discussion is proof that the science isn’t definitive because controversy and emotionally charged disagreement can only occur where definitive proof from science is lacking.

1B: Regarding prevention strategy, I took the (apparently controversial) position that someone age 65 with no familial history of CVD and no current symptoms of CVD should follow a lower-risk approach starting with CTCA testing before pumping their biology with powerful drugs causing large systemic effects. The only reason I posted to this thread is because that risk-prevention thinking process is woefully absent in a very pro-drug community that proudly pushes the envelope. This thread was overwhelmingly pro-statin as if all conclusions were settled science. The fact that statins work is proof-positive that they have powerful systemic effects. Introducing those complex systemic effects to a system that is already working perfectly well with no current signs of problem opens new risks. No drug is risk free. Are the risks of the drug and the systemic effects it causes justified when no problem exists?

Ultimately, that’s the core of the disagreement here. We can agree to disagree. Some people prefer to bet their personal biology on large population research taking statins with large systemic effects (as proven by their effectiveness), and I prefer to monitor and test before imposing large systemic effects with powerful drugs when my N-1 proves my personal system is absolutely not broken. In my mind, it’s an obvious risk/reward decision, but we can agree to disagree. We are both in full integrity as evidenced by our personal decisions.

The argument that monitoring is inadequate thus justifying “prevention” doesn’t hold water IMHO because CVD doesn’t roll in like a tidal wave where the first symptoms of the disease are “too late.” In that analogy, if you can see the wave, then you’re toast. Not true. Instead, CVD is more likely to advance across the system like a tide rising over time. You can see it coming if you watch for it. In that analogy, someone 65 with no symptoms and no history can safely monitor. The problem shouldn’t get away from them in any deleterious way. Getting a CTCA every three years along with annual blood tests monitoring a deep array of factors should give adequate warning of the onset of any change well before it’s “too late.”

Again, if you see that differently, then we can agree to disagree. We are both in full integrity by betting our personal biology accordingly.

2: Systemic vs. linear thinking: Another underlying complication to this discussion is interpretation of data. I spent my career developing trading and risk management systems for the financial markets. The financial markets are complex, dynamic systems similar in some ways to the systemic complexity of biology. Humans have a long and deep history of incredibly stupid conclusions to systemic problems based on linear analysis of data. I have seen incredible amounts of money lost to confident bets based on linear data analysis that appeared conclusive, but failed to respect systemic complexity and unknowable variables. I’ve learned how to work with dynamic, self-adaptive systems far less complex than human biology, and the biggest mistake humans routinely make is to mistake partial knowledge from limited research with definitive truth when more remains unknown than they’ll ever understand. As Mark Twain wisely quipped, “It aint what you know that will get you, but what you think you know that just aint so.”

I believe it is a common problem in these threads to overly weigh fragmentary knowledge as actionable, thus disrespecting all that is unknown. This is an understandable problem for this community given the nature of every Rapamycin user having to make the leap with only fragmentary knowledge. We’ve self-selected as a group that accepts these risks, me included. It’s why deep subject experts like Kaeberlein and Kennedy have stacks that are a tiny fraction of most community members. It’s always a risk/reward judgment call, and they have deeper experience with the systemic complexities and unknown biology than lay users. Each drug/supplement and each N=1 situation must be analyzed for risk/reward, and they’re all different. The MTOR and aging biology impact overwhelmingly favor Rapa IMHO across the large population. That decision is clear despite limited data and all that remains unknown.

However, CVD is different. The N=1 outliers matter to the risk/reward analysis, and the large population data has limited applicability to N=1 outcomes. CVD has been studied for many years, but they have not untangled the dramatic differences in outcomes across the population implying more remains unknown than known. All we have right now are correlations and relationships with some causal mechanisms, but we don’t know how those relationships of multi-variate factors interrelate to determine disease (or not) in each individual. The outliers in the data are proof that it’s not settled science, and the controversy in this discussion is proof that it’s not settled science. More remains unknown than known. There are people with high lipids and no disease, and there are people with low lipids that get disease. Some research shows LDL is only 30% correlated, so it can’t just be about “crushing it” since that low correlation shows it’s not causation.

So, as a risk manager who must make decisions about his N=1 personal biology, I (foolishly) chose to chime in on this thread where the general belief is to “crush it” with statins by offering an alternative risk management strategy.

Again, I’m not anti-statin. It’s a great drug that makes total sense in the right N=1 situation. This is about N=1 risk management, the correct application of large population research to individual biology, and not mistaking the little bit that we know from limited research for the vastness of all that remains unknown causing risks we are unable to quantify.

So the question is, “what is the best risk mangement strategy for your personal situation?”

It’s about making smart risk management decisions based on all known evidence while not mistakenly believing we know more than we do.

In the face of all that remains unknown and unknowable on this topic, I chose to advocate for CTCA testing to first identify the beginning of disease in its early stages before imposing powerful drugs that cause systemic changes to my personal biology. I’m choosing to respect the unknown risks when the known risks are well managed as proven by no evidence of disease. If the system isn’t broken and shows no sign of disease, then my position is you are increasing risk by taking powerful drugs that change a system that’s working just fine without them.

Again, others interpret the data differently. I’m okay with that and respect their interpretation. We can agree to disagree.

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#102

You use the word “proven” several times and imaging does not prove anything. The only proof is on autopsy - everything else is conjecture when it comes to disease burden. This to me is where your central argument breaks down. I have 30+ years of experience proving that imaging was wrong in probably 1000s of N=1 cases.

And you talk about risk of statins yet you never mention any that you are concerned about. I know you say this isn’t about statins, but it is about not treating elevated LDL and far and away the most common and best way to do that is with statins given their enormous track record.

While CVD does have ways of monitoring and there is a gradual buildup, plenty of people die despite monitoring. I have a patient who had negative everything until catheterization. He was 65 or so, college professor. He had advanced left main disease and he is quite lucky he didn’t wake up one day with a fatal MI.

You mention that plenty of people with low LDL get disease and that isn’t really true. The current thinking is that you just don’t build plaque with very low LDLs. In fact regression is common. Yes, some people have disease at moderate LDL, but below 50 or so, it is hard to get disease. Yes, there is heterogeneity in how people handle LDL but there is little doubt that the same person will have lower risk if their LDL is lowered. And it becomes near zero at very low LDLs.

I think the Lancet 2024 assessment of dementia risk factors should put any debate to rest. You can’t know what the LDL is doing to your brain. It is tied as the number one modifiable risk factor. And MRI is telling history not foretelling the future.

You can mention systems and faulty linear thinking or whatever. It is my opinion that imaging tells you an incomplete story. People are drawn to pictures. Everyone wants pictures. The only picture that matters is on a pathologist’s slide after you are dead. Ok, that is a bit morbid. But I can tell you the lay person puts way too much value in imaging. That is a fault of concrete thinking. Not doctor worth their salt will say you have no disease based on imaging. Because you don’t really know.

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