But, > only 10% of people with hypercholesterolemia received lipid-lowering therapy Wouldn't this be much higher in the UK cohort? Also, > The sex- and age-

But, > only 10% of people with hypercholesterolemia received lipid-lowering therapy Wouldn't this be much higher in the UK cohort? Also, > The sex- and age- specific levels of TC in the current study of Koreans were lower than those reported in other high-income countries, including Japan, England, and the US Which would reduce the effect (relative to what was found in the analysis of UK data) even further. I don't think it adds a whole lot to talk about the confounding variables of this nature - it's an observational study, so of course it will have all sorts of confounding variables. If you are going to make a strong case that controlling for a specific confounding variable would reverse the relationship though, you should quantify the impact. It's unclear to me that statin usage would make a large difference, given that the study notes it wasn't a popular treatment. My general feeling is that these types of studies tend to end up measuring overall health - given that most of the factors that lead to high cholesterol level were controlled for (BMI, physical activity, smoking status, drinking, etc) - and the average person in any population is relatively healthy and well-adjusted to the common diet, any large deviation from the norm in any direction statically makes it likely that the subject has some health issues. What would be interesting to see in a meta-study is whether the optimal level of cholesterol either was consistent across populations that had very different averages or it tends to be near the median in each population. The former would be evidence that it's an independently meaningful biomarker; the latter would be evidence that it's just measuring how normal you are.