Population aging leads to an increased incidence of coronary heart disease (CHD). Low‐density lipoprotein cholesterol (LDLc) and body mass index (BMI) are well-established determinants of CHD, both of which are complex phenotypes and shared lots of common risk factors. Besides, both obesity and high cholesterol have been involved in “paradox” phenomenon, defined as higher cholesterol or BMI being associated with an elevated incidence of diseases while paradoxically related to a reduced mortality 1, 2. Thus, it seems plausible to expect similar effects of these two factors on diseases. Nevertheless, emerging evidence found that LDLc and BMI were not always correlated, for example, findings from two large cross-sectional studies found that the association between BMI and LDLc was completely lost in population older than 60 years, indicating that the role of LDLc and BMI in diseases might not always stay in sync and probably varied by age [3]. A number of studies have investigated the age-specific role of LDLc in CHD but generated inconsistent results, and the influence of age was poorly demonstrated on the association between BMI and CHD 4, 5, 6, 7, 8, 9. To date, there is insufficient data discriminating the independent association of LDLc or BMI with the risk CHD across the lifespan.

The high prevalence of hyperlipidemia and obesity, as well as the demographic variation relevant to aging population, call for concerns to clarify the age-specific roles of LDLc and BMI so as to anticipate benefits that might be achieved via LDLc reduction or weight control at different ages. Hence, in this study, we aimed to explore how the relation between LDLc or BMI and the risk of developing CHD varied from mid-life through late-life. Given of the prior evidence regarding the impact of sex and metabolic disorders in the BMI-LDLc relationship and the known effect of lipid-lowering treatment on CHD, we also performed stratified analyses to explore whether the age-specific associations differ by sex, metabolic syndrome (MetS) and lipid-lowering drug use 3, 10.