Differential age-specific effects of LDL cholesterol and body mass index on the risk of coronary heart disease

Background Low-density lipoprotein cholesterol (LDLc) and body mass index (BMI) are not always correlated and their relationship is probably dependent on age, indicating differential age-specific effects of these two factors on health outcomes. We thus aimed to discriminate the effects of LDLc and BMI on the risk of coronary heart disease (CHD) across different age groups. Methods This is a prospective cohort study of 368,274 participants aged 38-73 years and free of CHD at baseline. LDLc and BMI were measured at baseline, and incident CHD was the main outcome. Cox proportional hazards model and restricted cubic spline (RCS) regression were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of exposure on CHD. Results Similar relationships of LDLc and BMI with CHD risk were observed in overall population but in differential age-specific patterns. Across the age groups of <50, 50-54, 55-59, 60-64 and >=65 years, the LDLc-CHD association diminished with the adjusted HRs decreasing from 1.35, 1.26, 1.19, 1.11 to 1.08; while no declining trend was found in BMI-CHD relationship with the adjusted HRs of 1.15, 1.11, 1.12, 1.13 and 1.15, respectively. The interaction and mediation between LDLc and BMI on CHD risk were only present at young-age groups. And the LDLc-CHD but not BMI-CHD association was dependent on sex, metabolic syndrome and lipid-lowering drugs use. Conclusion There were differential age-specific effects of LDLc and BMI on the risk of developing CHD, calling for future efforts to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD. What Is New? What Are the Clinical Implications? ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial N/A ### Funding Statement This work was supported by the Natural Science Foundation of Fujian Province (grant no. 2022J01706) and the Start-up Fund for high-level talents of Fujian Medical University (grant no.XRCZX2021026) to Dr. Wuqing Huang, and by the Start-up Fund for high-level talents of Fujian Medical University (grant no. XRCZX2017035 and XRCZX2020034) to Dr. Weimin Ye. The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The North West Multi-Centre Research Ethics Committee has approved UK Biobank study (REC reference: 11/NW/03820) and all participants signed informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data from the UK Biobank is available to researchers upon a data access application. * BMI : body mass index CHD : coronary heart disease LDLc : low- density lipoprotein cholesterol MetS : metabolic syndrome MI : myocardial infarction PERM : percentage of excess risk mediated RCS : restricted cubic spline RERI : relative excess risk due to interaction.