Eating butter is good for your heart. As long as your triglycerides and HDL (AKA "good cholesterol") are low, elevated LDL (AKA "bad cholesterol") is associated with lower all-cause mortality.
Maybe in some cross sectional or cohort studies with poor adjustment models we might see such a signal? Several states of poor health drive LDL down because of those diseases (e.g. having cancer can result in lower LDL, having a heart attack can massively lower LDL), so if we look at study designs that don’t take this into consideration, it can appear that high LDL is protective because of reverse causation.
However, I’m not aware of any evidence that takes this into account showing higher LDL associated with lower ACM. What’s your evidence for such a claim?
Yeah, this is a good example of what I’m talking about - you take a bunch of people at risk of diseases that lower LDL-c as a result of having that disease.
They actually acknowledged that reverse causation is a risk here and so ran a sensitivity analysis by excluding patients with less than 5 years of follow up (a nice way of saying “patients who died within 5 years of the LDL-c reading”), the idea being that if these results were likely being driven by reverse causation, you’d expect to see an attenuation of the results.
I’d point out that even if we didn’t, five years is a bit of a weird cutoff - plenty of LDL-c lowering diseases take much longer to kill the average person. Moot point though, because excluding those participants attenuated the result to the degree that the association with LDL-C and mortality became statistically insignificant.
Quite why the authors said “we’re aware that reverse causation is a risk factor, let’s run a test to check if it’s likely influencing the results” and then completely ignored the fact the results suggested it was influencing the findings, is anyone’s guess.
So yeah, basically huge confounder seems to be in play that likely explains the “paradox”.
However, I’m not aware of any evidence that takes this into account showing higher LDL associated with lower ACM. What’s your evidence for such a claim?