Association Between Total Cholesterol and All-Cause Mortality in Oldest Old: A National Longitudinal Study

Background: In the context of accelerated global aging, blood lipid levels are directly related to the health status of oldest old. The common sense is that lower serum cholesterol levels are better, as higher cholesterol levels increase the risk of cardiovascular disease. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over. Methods: In this retrospective longitudinal study, we selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome of our study was all-cause mortality. The univariate and multivariate cox regression analyses were used to estimate Hazard ratios (HRs) and 95% confidence interval values of all-cause mortality. To analyze further the relationship between total cholesterol and all-cause mortality, we stratified the participants into three groups (<3·40, 3·40-4·39, ≥4·39 mmol/L) base on the restricted cubic splines methods. The survival probability according to total cholesterol category was calculated using the Kaplan-Meier curves, and the log-rank test was performed to analyze differences between the groups. Findings: During the follow-up of three years, 282 participants died, 497 survived and 124 lost to follow-up. When the total cholesterol was used as a continuous variable, there was significant relationship between the total cholesterol and lower risk of all-cause mortality in the univariate (HR=0·85, 95% CI: 0·76-0·96; P=0·011) and multivariate(HR=0·88, 95% CI: 0·78-1·00; P =0·043) cox regression analyses. Based on the restricted cubic splines methods, the total cholesterol was converted from a continuous variable to a categorical variable. The populations were divided into three groups (<3·40, 3·40-4·39, ≥4·39 mmol/L) according to the total cholesterol categorized by cutoff values. Compared to the total cholesterol level of <3·40 mmol/L, populations in the total cholesterol level of 3·40-4·39 mmol/L (HR = 0·72, 95% CI: 0·53-0·97; P =0·029) and ≥4·39 mmol/L (HR =0·71, 95% CI: 0·52-0·96; P =0·029 ) groups had lower all-cause mortality in multivariate cox regression analyses and higher survival probability(log-rank P =0·018) in survival analysis. In addition, populations in the total cholesterol level of ≥3·40 mmol/L (HR = 0·71, 95% CI: 0·54-0·93; P =0·014) groups had a significantly lower risk of all-cause mortality and higher survival probability (log-rank P =0·006) than the populations in the total cholesterol level of <3·40 mmol/L groups. Interpretation: In oldest old aged 85 and older, serum total cholesterol levels are inversely associated with all-cause mortality. Total cholesterol < 3·40 mmol/L increases all-cause mortality risk in this age group, each 1 mmol/L reduction in total cholesterol increases the risk of death by 12% in this group. This finding suggested that total cholesterol should be maintained to acceptable levels ( ≥ 3·40 mmol/L) in oldest old to achieve longevity. Funding: Shanghai Three-year Action Plan for Public Health under Grant(GWV-10.2-XD13, GWV-10.1- XK15, GWV-10.1-XK18); Strategic collaborative innovation team (SSMU-ZLCX20180601); the National Key Research and Development Project (2018YFC1705100, 2018YFC1705103). Declaration of Interest: None to declare. Ethical Approval: The CLHLS study was approved by the research ethics committee of Peking University (IRB00001052-13074). All participants provided written informed consent.