Abstract

Abstract Background Limited evidence exists regarding the association between remnant cholesterol (RC) and both all-cause and cardiovascular mortality. Also, the effect of age on the association between RC and the risk of mortality in general population has not been studied comprehensively. Therefore, the aim of this study is to investigate how age modifies the relationship between RC and the risk of all-cause and cardiovascular mortality. Methods A total of 21722 participants aged over 18 years were obtained from the National Health and Nutrition Examination Survey (1999–2018) , with follow-up mortality outcomes records linked to the National Death Index (NDI) until December 31, 2019 and divided into two groups (<65 years old and ≥65 years old).Weighted multivariable cox proportional hazards models and weighted restricted cubic spline (RCS) were used to estimate the relationship of RC with the risk of all-cause mortality and cardiovascular mortality among American adults. The age interaction between RC and all-cause mortality and cardiovascular mortality was assessed. Restricted cubic spline (RCS) and sensitivity analysis were also used. Results During a median 110-month follow-up, a total of 3176 (10.77%) all-cause deaths and 1002 (3.22%) cardiovascular related deaths were recorded. A significant age interaction between RC and all-cause or cardiovascular mortality was found. After adjusting for multiple potential confounding factors, higher RC was associated with an increased risk of all-cause mortality[RC per unit increase Hazard Ratio (HR) 1.45, 95% Confidence Interval (CI) 1.16–1.81, p=0.001] and cardiovascular mortality (RC per unit increase HR 1.80, 95% CI 1.15–2.84, p=0.010) specifically in the younger age group but not in the older age group. Consistent findings were observed in restricted cubic spline analyses and sensitivity analyses. Conclusion In our study, we observed that the association between serum RC and all-cause mortality and cardiovascular mortality was modified by age. Specifically, higher RC levels were found to be significantly associated with an increased risk of all-cause mortality and cardiovascular mortality exclusively in patients below 65 years old. This novel finding warrants further confirmation through randomized controlled trials to provide robust evidence.

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