The Protective Impact of Residual Cholesterol on Mortality Risk in Oldest Old

Abstract Background: Residual Cholesterol (RC), similar to triglycerides, is recognized as an underlying mortality risk factor in the general adults,but it is unknown whether risks also increase with advancing age. Evidence regarding the effect of RC on cause-specific mortality risk among older adults, specifically the oldest old (80 years and above), are lacking. Methods: We encompassed 4,289 Chinese older adults from the Healthy Aging and Biomarkers Cohort Study (a prospective, community-based cohort study, 2008–2021). RC was calculated using the formula of fasting total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. The Cox proportional hazards models and Fine-Gray’s semi-parametric method for competing risks analysis were used to estimate the association between RC and all-cause and cause-specific mortality risk, respectively. Results: As compared with participants in the lowest tertile RC group, the adjusted hazard ratio (HR) for those in the highest tertile were 0.868 (95% CI: 0.784–0.960) for all-cause mortality. A significant inverse linear relationship between RC levels and the risk of all-cause mortality, indicating a consistent decrease in risk until a threshold of 0.88 mmol/L is reached. An increment of 0.1 mmol/L of RC was associated with a reduction of 3.4% in all-cause mortality risk and a 5.6% decrease in non-CVD mortality. The inverse linear association remained significant for the oldest old, but not younger older adults. Conclusions: In the oldest old, a higher concentration of RC was associated with a lower risk of all-cause and non-CVD mortality. The paradoxical association between higher RC and lower risk of mortality risk among the oldest old suggests that cholesterol-lowering therapy should be carefully considered for the oldest old with elevated concentrations of RC, as it may provide little to no benefit and could even be potentially harmful.