Association between Time-Weighted Remnant Cholesterol and Incident Cancer: A Population-Based Chinese Cohort Study

Background: Remnant cholesterol (RC) is becoming an increasingly well-recognized risk factor for cardiometabolic diseases. However, no study has explored the predictive role of RC in new-onset cancer. This study aimed to examine the associations between RC and time-weighted RC with incident cancer in the general population. Methods: This was a retrospective population-based study enrolling patients attending family medicine clinics in Hong Kong between 1st January 2000 and 31st December 2003 with at least three RC measurements during follow-up visits. The primary outcome was new-onset cancer. The secondary outcome was cancer-related mortality. Multivariable Cox regression was used to evaluate associations between baseline RC and time-weighted RC with outcomes. Results: A total of 75,342 adults (39.7% males, mean age: 62.5 years old) were included. During a median follow-up of 16.8 years, 8335 (11.1%) incident cancer and 4349 (5.7%) cancer-related deaths were observed. After adjusting for potential confounders, one mmol/L increased of time-weighted RC was associated with 41% and 62% higher risk of incident cancer (HR, 1.41; 95%CI, 1.26-1.57; p<0.0001) and cancer-related mortality (HR, 1.62; 95%CI, 1.43-1.85; p<0.0001), respectively. However, no significant association between baseline RC with risk of new-onset cancer (HR, 1.04; 95%CI, 0.82-1.31; p=0.768) and cancer-related mortality (HR, 0.85; 95%CI, 0.61-1.17; p=0.315) in the adjusted model. The association between time-weighted RC and incident cancer was significant regardless of age, gender, and remained consistent amongst those with baseline use of most cardiometabolic agents, as well as those complicated with most comorbidities. Conclusions: Higher time-weighted RC was associated with increased risk of new-onset cancer and cancer-related mortality amongst the general population. ### Competing Interest Statement G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are directly received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871. The remaining authors have no disclosures to report. ### Funding Statement The authors received no funding for the research, authorship, and/or publication of this article. ### 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: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKWC IRB) (UW-20-250) and complied with the Declaration of Helsinki. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are not available, as the data custodians (the Hospital Authority and the Department of Health of Hong Kong SAR) have not given permission for sharing due to patient confidentiality and privacy concerns. Local academic institutions, government departments, or nongovernmental organizations may apply for the access to data through the Hospital Authority's data sharing portal (https://www3.ha.org.hk/data).