4 ms·

> 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 tha

by darawk 5y ago

> 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.

sooheon 5y ago
> 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 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).
- lvass 5y ago
  That's just one disease, that one wouldn't expect to be associated with low cholesterol to begin with, though.
  - sooheon 5y ago
    There exist MR studies on cholesterol levels vs. longevity as well: https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14811 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.... These nits really aren't worth picking over when you haven't presented any RCT or MR evidence for your alternative theories.

by darawk 5y ago

sooheon 5y ago

> 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 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).

lvass 5y ago
That's just one disease, that one wouldn't expect to be associated with low cholesterol to begin with, though.
- sooheon 5y ago
  There exist MR studies on cholesterol levels vs. longevity as well: https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14811 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.... These nits really aren't worth picking over when you haven't presented any RCT or MR evidence for your alternative theories.