Statins lower all cause mortality. Statistically significant. Blue.
Risk ratio for a 0.5 mmol/l lower LDL cholesterol: 0.95 (0.92–0.99); p = 0.009
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In the absence of preexisting cardiovascular disease, statins have no benefit in primary prevention to lower all cause mortality rates. This appears to be true even in the presence of other risk factors.
It is, however, quite good for secondary prevention.
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Okay, interesting discussion.
I’ve now looked at all the trials.
All were about primary prevention. And in 2 studies of 11 were there people included with pre-existing disease, but not only (PROSPER and ASPEN). 9 of 11 trials were done with absence of preexisting cardiovascular disease.
Statins lower all cause mortality in primary prevention. Even without preexisting cardiovascular disease.
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The weight of the evidence in favor of statins is so high in my opinion that it does not even merit further discussions at this time.
I see no harm in taking them, in fact, quite the opposite. It is unlikely that any long-term, double-blind RCT is going to take place anytime soon. Until that happens and it proves statins are not beneficial, I will happily keep on taking my daily dose of atorvastatin.
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Absolute risk reduction of total mortality with statin usage is of the order of 0.8% and may not be due to its lipid reduction.
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Here’s a nice discussion on how much absolute risk reduction you’re getting out of it.
https://www.uspharmacist.com/article/statins-less-cv-risk-reduction-than-commonly-assumed
The ACM benefit is based on the amount of lipid reduction, for every 0.5 mmol/L LDL reduction a 5% lower ACM.
So it is precisely because of the lipid reduction.
Also remember these are short term trials. The MR and genetic studies show a very large decrease in ASCVD related events because of compounding benefits.
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I think you missed the point: “I see no harm in taking them, in fact, quite the opposite.”
Plus, my doctor whom I respect, prescribed them, I didn’t ask for them.
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I’m sure your cardiologist is very competent. Merely pointing out absolute risk reduction for purposes of discussion. Not attempting to diagnose or offer treatment advice.
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It depends anyway on treatment duration, background rate of events, level of LDL reduction, etc.
I would think one advantage of statins would be a redirection of cytosolic metabolism so that more acetyl-CoA is available for histone acetylation.
Indeed. Statins do behave as HDAC inhibitors which serves to increase histones acetylation and expression of p21 in human cancer cells. Could be useful in that regard as a cancer fighter, but of course unrelated to lipids.
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That’s an interesting point. If they only inhibit HDAC2, however, then I would think their effect on the availability of Acetyl-CoA is at least relevant. The level inhibition in the tens of micromolar is not out of line with many other HDAC inhibitors although the big question is the bioavailability of any one HDAC inhibitor.
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Are you concerned about acetyl Co A depletion with HDAC inhibition?
Yep glycine is another option - one can get a good amount from collagen peptides assuming tested no heavy metals
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I do agree there exists a lot of uncertainty regarding statin pleiotropic mechanisms, hence if patients not indicated and maybe high baseline risk with multiple risk enhancing factors - it’s difficult to predict for certain the actual all-cause mortality change in say 30 years.
That being said, you’re right that there isn’t any evidence for or against long term statin therapy in “healthy” people. Hence, if one already is on statins, there’s no real great evidence for it but I don’t see a reason to stop in absence of any clear side effects from the statin. I always emphasize “perfect” lifestyle factors first.
If one wants to bet on the LDL hypothesis there are plenty of other options to try first. Maybe one could consider soluble fiber/psyllium husk, glycine, and 100% cacao. I have doubts there is any significant possible harm from a quality diet rather than supplements. Avoiding very select types of saturated fats and processed oils (aldehydes and trans fats can form) may also be beneficial.
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I’m not a doctor, but out of all of the longevity/healthspan interventions, this is the most certain of them all IMO.
- Clear mechanism of action
- Mendelian randomization on mechanism, very positive results
- All cause mortality benefit in studies done, and primary prevention
- ASCVD benefit in studies done
- Genetic studies replicating similar results
- Log-linear causal relationships on LDL
“a lot of uncertainty about pleiotropy”
“LDL hypothesis”
“bet on it”
If this was an investment, I would invest 9.5 times out of 10.
If you don’t put other longevity/healthspan interventions under the same scrutiny and skepticism, especially now that there are also meta analysis of RCTS reviews showing ACM benefit:
Maybe check your biases.
Difficult to predict 30 years, no it’s not, if you extrapolate and use all available evidence which include very strong data from genetic studies and mendelian randomization. Can it be wrong? Yes. Unlikely? Yes, IMO.
Also I am not specifically talking about statins, but this entire area of apoB + non-HDL-c reduction.
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Long term studies of any kind of any kind of drug has never happened, and never will happen.
So it is about as useful to dismiss statins as anything else. We still take the other drugs, vaccines, and whatever else.
edit: are you also going to wait for 30 years until a hypothetical statin trial was completed from today?
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I totally agree.
There’s also citrus bergamot:
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Thats potentially an interesting paper. I am quite drunk at the moment so it is not a good time to go through that paper. However, my own experimentation which is primarily on myself is going quite well so I don’t think the idea that encouraging gene expression is bad is something I would agree with.
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