Statin Question

[integral]

I didnt want to derail that other topic.

Last night I had a thought about this and wanted the practitioners on the forum perspective on it. If we generalize like this "statins have the ability to reduce the risk of major cardiovascular events up to 10% in primary prevention and 5% in secondary prevention over 5 years"

For the 80%-90% of people where statins lowered cholesterol but the patients still suffered an event, how do we know statins didnt make the situation worse for them?

What if its a bell curve where some patients who have the correct genetics benefit from statins up to 20% of the population while 60% it did not benefit them and 20% it made there situation worse? But studies focus on risk reduction so it will show a 20% reduction in cardiovascular events but ignore or not track the patients whos situation got worse, its a blind spot? Are there any studies that do the reverse and check risk increase by removing the patients that benefited from it?

Also if the issue is systemic and cholesterol is not the issue, why are we focusing on reducing cholesterol? About half of all patients who have cardiovascular events have normal to low cholesterol. 

Edited May 11, 2023 by integral

[Michael569]

you might find this debate interesting if you want to geek out and go really deep on the topic. They cover everything from Cholesterol to APoB to statins and PCSK9 inhibitors as well as challenge the model of 10-year risk vs 30-year risk based on Alan's 2020 review

I thought this was a very mature and comprehensive discussion. 

 

[integral]

@Michael569 Great talk, I love these guys. Im not getting one part, he goes in great length to explain how ApoB is a better risk assessment and has a very detailed explanation of how it all works, they seem to have good case to transition and advance the industry to move in this direction. Then at 1:08:52 they discuss people with normal to low risk assessment for ApoB but still contract Atherosclerosis young and have events young, he then say "I don't know, this is where research needs to be done". That would then mean his model of how and why Atherosclerosis happens within the human body is incomplete. Something is causing the ApoB protein to bind to the artery walls for some people and not others. That is what needs to be figured out, there is no model to be made with out this piece of the puzzle.

The discussion about the guidelines was fantastic. The only criticism I have is they are 100% focused on data, studies, scientific evidence that represents the tip of the iceberg of known information on these topics. As far as I'm concerned no real effort was put into any of this yet, minimal innovation, the financial incentive is not aligned with health yet and until that happens there will be no real advancements in knowledge or technology. Its the stone age of health care. The tools they have to work with is abysmal and they lack the imagination to see how behind there tools are and the industry is.

Create a machine that can see everything in the blood and display it in an app, on the app select the things you want to filter out and hte machine will filter out only does compounds. The application for this would be a endless, completely revolutionize health. Instead we have a archaic dialysis machine. INOVATE, DO SOMETHING! We need better tools.

There is a multi billion dollar untapped consumer health care boom around the corner. 

Where is the innovation and creative thinking? There spending all there intelligence micro progressing a sub field of a sub field and then publish a research paper on it. Instead of focusing on the 10x to 100x improvements we could be making in this domain.

The ball cant start rolling yet because the people attracted to health care careers are ISTJ and ESTPs and they love there comfort zone. Once the health care technology boom really starts to take off vai the incentive of consumer products more intuitive types will move into the domain rapidly progressing things. 

Edited May 12, 2023 by integral

[Michael569]

9 hours ago, integral said:

That would then mean his model of how and why Atherosclerosis happens within the human body is incomplete

Ofcourse it is incomplete. Even Alan at one point admits "I don't know where heart disease starts" and he says "I think it is in the proximal Aorta" 

So in a way, even the specialists on cardiology don't fully understand the disease. Being able to admit the limitations of one's knowledge is a very humble trait, this is why I loved this conversation, because they are both humble enough to admit that.  Basically, anyone in health who tells you they know it all are so full of shit that even their burps smell like farts. 

That's fine, our knowledge is evolving and new studies are coming out each month. I really like when Alan criticises the types of studies coming out right now - mechanistic trash focusing completely on the wrong stuff,  on rodents,  with cool pathways so that they get published and shared on social rather than something that would actually advance the field. 

9 hours ago, integral said:

The tools they have to work with is abysmal and they lack the imagination to see how behind there tools are and the industry is.

The tools we have right now are the tools we need. Not everything that is new is necessarily better. Diagnostic tools are pretty good, they are standardised and can usually predict a disease fairly efficiently. Of course with the application of genetic medicine and nano tech, the field is likely to advance even further as long as they are applied properly. I'm all for continuous advancement but not at the expense of practicality (e.g. lot of companies nowadays sell tests and assessments which are just fucking garbage, inaccurate, irrelevant and completely misleading the patient down numerous dead ends. 

Not just that but I am sometimes getting clients who worked with naturopaths and functional med practitioners who send them for overpriced shitty tests like Organic Acids, complex methylation panels, all sorts of weird guts tests, hair analysis tests - because they have no idea what to do with those people so they keep coming up with ways to avoid admitting that. Of course in the end the client is 5 grant shorter and not an inch closer to getting better and on the top of that the reputation of the industry is slowly sinking. 

So yah, new isnt always better. We need to balance the new with the proven-to-work

 

Edited May 12, 2023 by Michael569

[LSD-Rumi]

@integral Cardiovascular disease is multifactorial. It is caused by inflammation, high sugar levels, high blood pressure, high cholesterol, and lipids level, and also genetics play a huge role too. All these things make what we call atheroma in blood vessels, this structure is a collection of lipids and calcium in the body of the blood vessel and it is very fragile. At some point, it explodes and causes a cardiovascular event. So by lowering lipids, lowering blood glucose, and controlling blood pressure, you decrease the progression and enlargement of this atheroma, but once it is there, it is there, you can just delay its progression

22 hours ago, integral said:

. If we generalize like this "statins have the ability to reduce the risk of major cardiovascular events up to 10% in primary prevention and 5% in secondary prevention over 5 years"

Statins are very effective, don't undermine them.

"The Lancet in 2018 included 28 randomized controlled trials with over 186,000 participants and found that statin therapy was associated with a 21% relative risk reduction in major vascular events (i.e., nonfatal myocardial infarction, coronary heart disease death, stroke, or coronary revascularization).

Another meta-analysis published in the Journal of the American Medical Association in 2019 included 43 randomized controlled trials with over 300,000 participants and found that statin therapy was associated with a 27% relative risk reduction in major cardiovascular events (i.e., major coronary events, strokes, and coronary revascularizations)." chatgpt

22 hours ago, integral said:

About half of all patients who have cardiovascular events have normal to low cholesterol. 

And that's why it is called a multifactorial disease. If you have high cholesterol levels, you get treated with statins, if you don't, other factors are addressed.

 

[undeather]

Quote

Ofcourse it is incomplete. Even Alan at one point admits "I don't know where heart disease starts" and he says "I think it is in the proximal Aorta" 

I dont think coronary heart diesease starts in one particular area.
In fact, one of the most surprising facts about heart catheter or ultrasound examinations is how unintuitively scattered plaque-formations can be in certain patients. You see someone with a completely fucked up left main coronary artery (multiple high grade blockages) but an almost juvenile right coronary artery with zero signs of atherosclerosis. Patients whose aorta looks like a corroded ruber tube, but whose coronary arteries are seemingly untouched. Others who show zero sign of plaque formation in their carotids, but completely end stage atherogenesis in their heart. 

There are of course clusters, for example in bifurcation types - where you clearly see one kind of plaque formation much more often than others:

Also, in general - if you find atherosclerosis in one place, the chance is high that you have it somewhere else as well (its a systemic occurance). That said, there is a big individual component which makes it really difficult to predict where it might cause serious problems down the line. My heuristic is that our individual vascular anatomy is the main predictor where plaques might gain a foothold faster. Differences in flow dynamics which make the endothelium in one specific place more susceptible to dysfunction - where it's almost prone to create an inflammatory response and ApoB emplacement. Besides that, there seem to be "structural" weak spots, which could stem from saltatory downregulations of protective fibers (like elastin) in our arterial tissues. All this and much more will at the end decide where damage occurs fastest.

But then again, this is somewhat speculative  

Edited May 12, 2023 by undeather

[integral]

2 hours ago, LSD-Rumi said:

"The Lancet in 2018 included 28 randomized controlled trials with over 186,000 participants and found that statin therapy was associated with a 21% relative risk reduction in major vascular events (i.e., nonfatal myocardial infarction, coronary heart disease death, stroke, or coronary revascularization).

Another meta-analysis published in the Journal of the American Medical Association in 2019 included 43 randomized controlled trials with over 300,000 participants and found that statin therapy was associated with a 27% relative risk reduction in major cardiovascular events (i.e., major coronary events, strokes, and coronary revascularizations)." chatgpt

Yes but out of the 79% of people who did not benefit from statins, what did statins do to there bodies and what percentage of them statins made there situation worse? What percentage of people in does studies did statins have no benefit and gave them debilitating symptoms, is it around 21%? There is a bell curve and we are only looking at risk reduction, meaning we only look at the one part of it. How do we know for 21% of people statins changed there hormones that then changed there eating habits or exercise habits causing a multifactorial change in there life style. Why did some people benefit and not others? Did statins cause behaviour changes for some people that then reduced there risk? If we give someone caffeine and nicotine supplement what is the risk reduction? There are endless experiments we cant conduct because its not ethical enough to conduct them because participants will need to die from ineffective treatments. 

Edited May 12, 2023 by integral

[LSD-Rumi]

34 minutes ago, integral said:

Yes but out of the 79% of people who did not benefit from statins,

No! you got it wrong. The percentage of 27% reflects how much reduction in disease risk happened in the majority of the population that was studied.

Edited May 12, 2023 by LSD-Rumi

[integral]

16 minutes ago, LSD-Rumi said:

No! you got it wrong. The percentage of 27% reflects how much reduction in disease risk happened in the majority of the population that was studied.

How is a general statement like this useful at the individual level? For some people at the individual level statins did not reduce there risk and could of exasperated the problem by increasing stress hormone. Where is the data on this? 

[Michael569]

1 hour ago, undeather said:

Differences in flow dynamics which make the endothelium in one specific place more susceptible to dysfunction - where it's almost prone to create an inflammatory response and ApoB emplacement. Besides that, there seem to be "structural" weak spots, which could stem from saltatory downregulations of protective fibers (like elastin) in our arterial tissues. All this and much more will at the end decide where damage occurs fastest.

can you tell more about this: What are the factors that influence endothelial integrity? Is that genetically given? Is it because of the sheer stress of the ejection from the left ventricle or more like wear & tear over time? 

How (and why) do elastin fibres in certain areas become weaker? Does it have anything to do with diet, antioxidant status, and collagen repair? What are things we know that weaken these fibres? 

Is this where particle size comes in? 

What about systemic effects of things like histamine on endothelial permeability? 

Edited May 12, 2023 by Michael569

[LSD-Rumi]

2 hours ago, integral said:

How is a general statement like this useful at the individual level? For some people at the individual level statins did not reduce there risk and could of exasperated the problem by increasing stress hormone. Where is the data on this? 

Dude, this is the percentage of how much decrease in disease risk experienced by the average of patients, some benefit more and some benefit less. Now, every drug has side effects and those are not major unless in rare cases. The benefit outweighs the risk by a large margin. Statins are demonized by the public for no reason, they literally save lives. hypertension drugs may cause depression for example in 5% of patients, so do we stop using them, No, unless depression occurs.

Maybe we could do more research on who's expected to benefit less from these drugs but until then they will remain a pillar in the treatment of heart disease 

[undeather]

3 hours ago, Michael569 said:

can you tell more about this: What are the factors that influence endothelial integrity? Is that genetically given? Is it because of the sheer stress of the ejection from the left ventricle or more like wear & tear over time? 

How (and why) do elastin fibres in certain areas become weaker? Does it have anything to do with diet, antioxidant status, and collagen repair? What are things we know that weaken these fibres? 

Is this where particle size comes in? 

What about systemic effects of things like histamine on endothelial permeability? 

In general mechanical (i.e high blood pressure) and chemical (i.e high blood sugar-> glycation) stressors,
As you can imagine, it's an incredibly complex mechanism that over time wears down the structural and functional integrity of your blood vessles. This then leads to  up-regulation of adhesion molecules, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, platelet activation, cytokine elaboration, and vascular smooth muscle cell proliferation and migration.
Basically all that shit you dont want

It's nature & nurture. Nature being genetics - meaning your individual tissue specific resistance which is mainly defined by your genetics. Then of course nurture - which are all the risk factors that are invoved in atherogenesis.

Blood flow in arteries is not laminar, but pulsatory. Your left ventricle pumping creates a "puls wave" and your blood moves accordingly. The strength of that pulse wave (pulse pressure)  and the total pressures (general blood pressure) will define the mechanical tear on your artieries. Damage occurs over time of course.

Just like your stomach musculature is not perfectly consistent -> which might create hernias ..some parts of your arteries might not be consistently vested with the same amount of protective fibers! This is HUGELY speculative though and only based on some histological studies I read I have no idea how antioxidant status and collagen repair could play a role in that.

Particle size comes in later in the process of atherogenesis itself. A huge topic in itself.

OH boy, histamine and endothelial permeability is very complex and we need would need whole thread for that topic alone. 
There seems to be a strong correlation with histamine, endothelial permeability and your general cardiovascular diesase risk. It makes sense mechanistacally ( kind of ) but we need more data to act clincially. I have my own heuristic for that, maybe I can go deeper into that in the future - but it would exhaust my time window for now

[Schizophonia]

3 hours ago, LSD-Rumi said:

Dude, this is the percentage of how much decrease in disease risk experienced by the average of patients, some benefit more and some benefit less. Now, every drug has side effects and those are not major unless in rare cases. The benefit outweighs the risk by a large margin. Statins are demonized by the public for no reason, they literally save lives. hypertension drugs may cause depression for example in 5% of patients, so do we stop using them, No, unless depression occurs.

Maybe we could do more research on who's expected to benefit less from these drugs but until then they will remain a pillar in the treatment of heart disease 

Why not change your diet rather than taking and promoting a drug that will drastically impair your recovery abilities.

[integral]

6 hours ago, LSD-Rumi said:

Dude, this is the percentage of how much decrease in disease risk experienced by the average of patients, some benefit more and some benefit less. Now, every drug has side effects and those are not major unless in rare cases. The benefit outweighs the risk by a large margin. Statins are demonized by the public for no reason, they literally save lives. hypertension drugs may cause depression for example in 5% of patients, so do we stop using them, No, unless depression occurs.

Maybe we could do more research on who's expected to benefit less from these drugs but until then they will remain a pillar in the treatment of heart disease 

It doesn't work this way in practice, each case is different the individual is everything and your going to end up with major mistakes using generalized statistics. The data must break down each individual case to develop the correct strategy for diagnosis. How can the data not focus on the most vital components needed to differentiate the individuals? Lets forget statins as they appear to be regarded as the holly grain. The approach of using these generalizations to hedge your bets leads to giving people medication they don't need that worsen there situation. In the other thread Leo made it clear T3 and T4 does not work for him he said because its a systemic issue, but that testimony isn't really taken seriously. When the average person takes medication that don't help them they are far to unconscious to accurately asses that and never get off of it. 

Random testimony: My aunt at her second pregnancy testes low and was put on thyroid replacement. After that she developed intense panic attacks and her mental health diminished over time. She kept getting retested and they kept increase the dosage to keep her in range. Her life was absolutely destroyed by this approach. A very similar situation happened to me and when I explained to the doctor that I was 100% sure the thyroid hormone was causing my panic attacks as I'm highly stable person that have never had a panic attack before in my life. They told me i was crazy, pointed to there diploma hanging on the wall, explained how ranges work and literally yelled me out of there office fully offended that I challenged them, This happened twice in person and is happening again on this forum. I got off the medication, the daily seizers reduced every day over a period of 2 weeks until it completely stopped and I went normal. I got retested many times and my thyroid hormone is perfectly fine. I only experience seizers during the period I was taking it, so i know it was the medication, i also experienced a many bodily changes and health problems because of this event that cant be reversed. So then why was I initially put on thyroid hormone? Because 1 time I got tested and it was low so they put me on it following there guidelines. This kind of thing is happing at scale and why there is a over prescription epidemic. I told my aunt that her thyroid medication was causing the panic attacks and she of course said "I trust in doctors". The other day at 60 my father who gets tests every 2 weeks for years tested low once in 45 years, they of course instantly put him on replacement hormone. 

Edited May 12, 2023 by integral