The association between time-weighted remnant cholesterol and cardiovascular and non-cardiovascular mortality: A population-based cohort study

Background: Remnant cholesterol (RC) have been suggested as a significant mediator of atherosclerotic cardiovascular diseases. However, the relationship between RC with cause-specific mortality in long-term remained uncertain. This study aimed to investigate the association between time-weighted RC and cause-specific mortality outcomes. Methods: This retrospective population-based study enrolled patients attending family medicine clinics in Hong Kong between 1st January 2000, to 31st December 2003 with at least three RC testing results during follow-up. The time-weighted RC was calculated by the products of the sums of two consecutive measurements and the time interval divided by the total time. The primary outcomes were all-cause mortality and cause-specific mortality outcomes. Cox regression and marginal effective plots were applied to identify associations between time-weighted RC and mortality. Results: A cohort of 75,342 patients (39.69% males, mean age: 61.3 years old) with at least three valid RC test were included. During up to 19 years of follow-up, in the multivariate model adjusted for demographics, comorbidities, medications, and time-weighted laboratory results, time-weighted RC was associated with all-cause mortality (Hazard ratio [HR]: 1.41; 95% Confidence Interval [CI]: 1.35-1.48) but not RC (HR: 0.99; 95% CI: 0.89-1.10). Time-weighted RC was also associated with increased risks of cardiovascular-related mortality (HR: 1.40; 95% CI: 1.27-1.54), cancer-related mortality (HR: 1.59; 95% CI: 1.43-1.77), and respiratory-related mortality (HR: 1.33; 95% CI: 1.20-1.47). The exploratory analysis of the cause of death demonstrated that time-weighted RC was associated with Ischaemic heart disease, cerebrovascular-related and pneumonia. Conclusions: Time-weighted RC was independently associated with all-cause mortality and cause-specific mortality outcomes amongst the general population. Keywords: Cause-specific mortality, Low-density lipoprotein, Very-low-density lipoprotein, Intermediate-density lipoprotein, Remnant cholesterol, Atherosclerosis, Cardiovascular disease