And an N of 1 "experiment" on whoever wrote this.
anybody in the medical field able to give some report on state of the art CV research ?
Heart disease is largely solvable from a biomedical standpoint: we have accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, precision nutrition, and highly effective next-generation drugs (PCSK9 inhibitors, lepodisiran, etc).
But practically speaking, heart disease remains the #1 cause of death due to bottlenecks in care delivery: e.g., 46% U.S. counties have no cardiologists, providing guideline-recommended preventive care would require ~27 hours per doctor per day, and incentives are misaligned (health systems profit when hospital beds are full, not from prevention).
1. Check your ApoB, Lp(a), hs-CRP every 4 months
2. Feed that into a current-gen LLM and ask it to tell you what drugs to take and at what dosages
Would that solve about 90% of the issue?
Supposed that we have an incentive aligned health care system. What would that look like?
I think one outcome is that the healthcare system eventually expands due to population growth and less death. Accidents happen, rare cases become more common, even as we get good at fixing or preventing them.
Lipo(a) is genetic, apparently either you have it or not.
Small dense ldl is caused apparently (not a biologist) from high triglycerides, one cause of which is high sugar diet.
I’ll eat a healthy diet, exercise, and live a life without persistent diarrhea. I’ll take statins if/when they are medically necessary, and no sooner.
The benefit of statins is to not only lower LDL cholesterol, but also inflammation, which is now actually a stronger risk factor for cardiovascular disease than cholesterol: https://www.empirical.health/blog/inflammation-and-heart-hea...
Layering PCSK9 inhibitors, ezetimibe, and statins can lower ApoB/LDL cholesterol by 85–90%, which would have been unheard of until recently.
On the horizon, drugs in clinical trials lower Lp(a) (the strongest hereditary risk factor for heart disease) by 94%. Currently, there are four RNA-based drugs in trials that effectively silence the gene that makes Lp(a) in liver cells: lepodisiran, olpasiran, pelacarsen, and zerlasiran.
> Concerns about statin effects on the brain, such as cognitive impairment or dementia, are unfounded
https://www.health.harvard.edu/heart-health/what-are-the-ris...
But I have high Lp(a) and so I'm prescribed a baby aspirin every other day. This counteracts the Lp(a) clotting effect but doesn't fix its genetic cause.
It's a journey.
It was such a strange feeling. It's a weird feeling to know you're brain just isn't working as it has always worked.
Do you have any info on good ways to nail down personal sources of inflammation relevant to cardio health, or do you think that just general anti-inflammatory diet/habits is the best we can do right now? We were hunting down a source of mold in our house recently due to some blood markers recently, which got me thinking about inflammation sources and cardio health (we found a big patch of mold between our floors and removed it, blood markers immediately improved).
For the average person, diet and lifestyle choices could be enough, but adherence can be difficult. Monitoring LDL as an imperfect but useful marker and then introducing low-dose statins on a sliding scale proportions to severity is a good idea.
Statins are not completely side effect free (no medication really is) but they’re generally well tolerated. Statin side effects are an interesting area of research because they have a very high nocebo effect rate: People hear so much about statins and their side effects from popular media that when they’re prescribed a statin in older age they start thinking everything is a side effect of the statin. There are some actual known side effects of statins which scale with dose and some of which can be maybe offset by supplements like CoQ10, but the side effects are generally mild. I’d take the side effects over heart disease after watching some older family members struggle and then die due to heart problems.
This is not pedantry, this is a vital problem of hundreds of millions of currently living people, many of which don't even know their own status.
I believe this can be done in the near future, there are some interesting initiatives in this direction, but it is very much not a solved problem.
Taking satins is proven to reduce heart disease rates, but there are lots of other drugs that lower LDL... many with much more efficacy than satins.
These non-satin drugs do not reduce heart disease rates significantly.
There something else going on here. High LDL is correlated with the development of heart disease, but it does not cause heart disease. Satins do reduce the risk of heart disease and they do reduce LDL, but their positive effect on heart disease rates is not caused by reduced LDL.
You realize this sentence is an oxymoron?
Unless you meant to say "it does not cause the development of heart disease". I agree correlation is not causation.
Edit: this was written before OP edited their comment
No it isn't.
Think of heart disease as slow, long-term damage to the cardiovascular system, and cholesterol is what the body uses as a bandaid.
If you have a lot of LDL cholesterol available, your body will use a lot of it, and you'll have stiffer arteries. If you don't have much available, it takes longer for the bandaids to build up.
This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
> This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
That’s one potential explanation, but I don’t think it’s the most likely one. We tend to see non significant ACM in smaller, less powered trials, or those with lower LDL-c lowering. ACM is simply a less sensitive endpoint - if you have a treatment that reduces CVD incidence, then the “CVD incidence” endpoint will give you significant results with fewer CVD event differences between study arms compared to ACM since your power to detect differences is diluted by other fatal events that aren’t affected by statins (cancer, motor accidents etc).
Across different genetic variants, lower lifetime LDL -> lower risk of death. Check out figure 3.
The causality of LDL -> plaque buildup -> 55-60% [1] of heart disease related deaths is also well understood, so it seems clear to me that preventing plaque buildup in the first place prevents over half of heart disease related deaths.
Would like to know if you disagree, "Minimize LDL at all costs" goes current mainstream medical guidance, so I'd like to disconfirm my beliefs if possible.
[1] Number from deep research.
A clinical score changing with treatment is not unconfounded by mendelian randomization. When the genetics are clearly more complex than what you are mathematically randomizing for, the control doesn't solve the confounding. eg you haven't suddenly "proven" the effects are non-genetic. We already knew heart disease is non-mendelian. But showing something is non-mendelian doesn't mean you've shown it's not genetic. I hope that clarifies, because I'm not sure I can explain it to you in simpler terms.
This is quite the tone to take when the actual point being made has demonstrably sailed over your head, considering the reference provided to you explains it very clearly.
Which is more likely - nigh on every lipidologist, cardiologist and nutrition researcher is wrong, or you might have made a mistake yourself?
> Mendelian is characterized by effects having strong influence from a single gene. Heart disease is clearly more complex than gene -> heart disease
This seems like a misunderstanding. A single SNP clearly can affect CVD risk, that’s precisely what the paper shows. The assumptions required for an MR study to be valid do not include “the outcome must only be affected by a single gene and no other gene”. It’s required that there’s no pleiotropy present in the exposure (I.e. the SNPs). The exposure here isn’t heart disease, it’s SNPs that affect LDL-c levels, and the outcome being measured is CVD. So your point doesn’t pose an issue for the study and the inferences it makes.
But honestly - just read the paper. I think both that paper and the EAS consensus paper are very approachable.
The cited study addresses this, which is why I pointed to figure 3. They argue that if genes were causing heart disease not through LDL in any meaningful way, you wouldn't expect such a clean dose-response consistency across different genetic variants - it would be more jagged.
[1] https://en.wikipedia.org/wiki/Mendelian_randomization#Defini...
Here is a simple primer on mendelian randomization: https://www.psomagen.com/blog/what-is-mendelian-randomizatio...
Please review the key principles and assumptions section. Using MR to control for genetic confounding of heart disease fails all assumptions. Thats why it quite directly does not follow.
This is why the paper presented does not support the claim that LDL is the sole source of heart disease. I'd be interested to hear what the authors of that paper (which is legitimate) think about it being used to support the OP's claim because "mendelian randomization".
Is that what we were arguing about? I guess it was. At some point in thinking about this my frame must have shifted into agreement with you. Of course there are other causes of heart disease besides LDL, like blood pressure, duh. The smooth dose response is about the particular gene not being linked to heart disease through something other than LDL, roughly.
In general, Ference’s explanation just seems more parsimonious than Schooling’s. It’s possible that they’re right, but I think they would need to show that the specific genes in Ference’s study are affected by age in this way.
I wouldn’t claim to be a great expert in MR, though. I can just about keep up with surface level understanding of them but once you get into the nitty gritty stats, pleitropy testing etc it’s a bit over my head tbh.
- LDL / ApoB
- Blood pressure
- inflammation (hs-CRP)
- Insulin resistance (HbA1c)
- Lp(a): strongest hereditary risk factor.
- eGFR: a measure of kidney function
Non-statin drugs like PCSK9 inhibitors have been shown to reduce heart attacks, strokes, and other cardiovascular events on top of statin therapy. One randomized control trial was FOURIER in 2017: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664Unfortunately, our biology isn't perfect.
Before hoping for a miracle, may I suggest adding more walks into your week?
I think your comment really owes the rest of us more explanation of this part.
As someone who rolled poorly on those genetic dice, I would like to complain. But also, disregarding a factor that impacts 20%[1] of the population seems disingenuous.
[1] - https://familyheart.org/family-sharing-tools/high-lpa-family...
I’m not saying either side is right but when it comes to your health why not evaluate as many opinions as possible.
I recently asked my doctor at Stanford - a pretty expensive hospital but one of the top cardio hospitals in the country - to get me an APoB test. He said that it may not be covered by insurance.
So instead I spend $360 or so on a year worth of biomarkers from Function Health that included ApoB and others
The author addresses a lot of the obvious gotcha points I see in the comments.
Although I don't think the author realistically explores the downsides of statin use, papering over the common side-effects.
- The blog seems to be associated with this Twitter account: https://x.com/sichuan_mala. That person seems to be a good friend of Cremieux¹.
- The article seems to have originally been published/unpublished in 2024 https://x.com/cremieuxrecueil/status/1922743591924899962
- It was only re-uploaded in September 2025 (?). There's some discussion of the claims under a tweet by Cremieux who announced the re-upload: https://x.com/cremieuxrecueil/status/1974990143544287715
sghiassy•1mo ago
My bet is close to none
agumonkey•1mo ago
noitpmeder•1mo ago
medstrom•1mo ago
bilsbie•1mo ago
WillAdams•1mo ago
Aurornis•1mo ago
Even without medications, we’ve had enough knowledge about diet and lifestyle factors that the average person (excluding generic abnormalities that lead to abnormally high risk) could reasonably avoid heart disease through lifestyle and diet alone. That’s easier said than done for a lot of people in the modern world, so it’s good that we have a few different medications on top of that knowledge.
dubeye•1mo ago
So it comes down to definition of 'resaonably'. diet and excercise will 'reasonably' reduce risk of most disease.
Aurornis•1mo ago
Same with medications? It’s well known that medications don’t eliminate risk.
For the average person without genetic outlier risk, perfect diet and exercise would definitely make heart disease a non-issue in their lifetime.
The risk your cardiologist is talking about is probably the risk that you have one of those genetic outlier conditions that require medication regardless of diet.
brandonb•1mo ago
From a biomedical standpoint, we have highly accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, knowledge of nutritional biochemstry, and next generation drugs like PCSK9 inhibitors and lepodisiran that can lower ApoB and Lp(a) by 90%. So there's no fundamental reason why cardiovascular disease has to be in even the top 10 causes of death.
Practically speaking, providing guideline-recommended preventive care would require ~27 hours per doctor per day. And the incentives are misaligned: health systems profit when hospital beds are full, so they lack the business model to actually invest in prevention.
So it's a clear illustration of a systematic gap between research and care delivery.
lm28469•1mo ago
Because most people don't give a shit about their health, no amount of pills will save you if you eat like the average american.
vladgur•1mo ago
loeg•1mo ago
vladgur•1mo ago
I’m not in love with the idea of sharing my biomarkers with multiple health-tech companies and really want a self-hosted solution to import biomarkers from multiple sources such as Apple Health, arbitrary csv and jsons while avoiding duplication.
Claude Code is something that will make this dream a reality for me pretty soon.
Do you have any tips on biomarker data design or import gotchas?
brandonb•1mo ago
vladgur•1mo ago
Im hoping to use LLMs to help with this process.
Will try to use LOINC dataset to standardize against
dubeye•1mo ago
the mainline guideline is more exercise and better diet which is the treatment to much more than just heart disease. that's not something 27 hours of doctors a day can provide unless you give them guns
the treatments reduce risk, but they don't change the fact the human body is very reliant on the heart and increasingly vulnerable to cardiac death with age, even with perfect biomarkers
dogmatism•1mo ago
it would take a lot more than that. Ain't no doc got all that time to go through all this with every person who should take cholesterol lowering medicine but wants to argue their internet sourced bs
lm28469•1mo ago
https://ec.europa.eu/eurostat/documents/4187653/10321616/dea...
https://ec.europa.eu/eurostat/statistics-explained/images/th...