Please enlighten us how you know statin health effects are 100% related to the fact their usage happen to reduce TC measurements, as your entire post assumes that.
Alternative hypothesis: high cholesterol is correlated (a small part of TC is from eating) with some adverse medical condition that statins are effective against. From this cohort, statin users measure lower cholesterol and die less. That lower cholesterol is always desirable and we should stop eating eggs would make absolutely no sense.
However, logically my post does not entirely rely on knowing the precise in vivo mechanism of statins and their causal health effects. We only need to see that in RCTs, lowered cholesterol doesn't cause increased mortality as these observational studies would suggest. That is a pretty direct test of the null hypothesis.
edit re your alternative hypothesis: what is this underlying adverse medical condition, and how is it resolved by statins? Every source I can find agrees statins work straightforwardly by inhibiting biosynthesis of cholesterol in the liver.
> However, logically my post does not entirely rely on knowing the precise in vivo mechanism of statins and their causal health effects. We only need to see that in RCTs, lowered cholesterol doesn't cause increased mortality as these observational studies would suggest. That is a pretty direct test of the null hypothesis.
It doesn't quite prove that, though. It proves that statins do not increase mortality risk on net. But it doesn't prove that reducing cholesterol by other means wouldn't increase mortality risk. It's possible, for instance, that lower cholesterol does increase mortality, but that statins are offsetting that increase in some other way.
> it doesn't prove that reducing cholesterol by other means wouldn't increase mortality risk. It's possible, for instance, that lower cholesterol does increase mortality, but that statins are offsetting that increase in some other way.
It's within the realm of possibility, but very unlikely given the state of the evidence.
Ok, ignore statins because that seems to be a trigger. Another way to test this hypothesis is to look at people with polymorphisms in their lipid regulation genes that cause different cholesterol levels, ranging from familial hypercholesterolemia to the opposite, lifelong low cholesterol. Drugs don't come into this, so it's not an intervention trial or RCT, but it's called a Mendelian randomization trial. Here's one: https://www.jacc.org/doi/full/10.1016/j.jacc.2012.09.017
> All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I2 = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10−19).
If you don't assume we don't know nearly anything, you're bound to jump into some early and bad conclusions. I have no idea what such condition may be. Heck, a year ago we thought the human body had a different number of bones than we do now. We definitely do not understand how cholesterol in the diet or otherwise affects health, and using statin studies is a really long shot.
I think you have an axe to grind re: dietary cholesterol, which I have made no statements on one way or the other. Don't read more into my post than what's there.
Alternative hypothesis: high cholesterol is correlated (a small part of TC is from eating) with some adverse medical condition that statins are effective against. From this cohort, statin users measure lower cholesterol and die less. That lower cholesterol is always desirable and we should stop eating eggs would make absolutely no sense.