Trajectory of Total Cholesterol in The Last Years of Life Over Age 80 Years. Cohort Study of 99,758 Participants

Background: Epidemiological studies suggest that lower total cholesterol (TC) may be associated with higher mortality. This study aimed to evaluate whether a decline in total cholesterol before death might account for the association of TC with mortality over age 80 years. Methods: Cohort study using primary care electronic health records of 99,758 participants aged 80 to 105 years from the UK Clinical Practice Research Datalink (CPRD). Hazard ratios (HR) for all-cause mortality were adjusted for age, gender, frailty, comorbidity, blood pressure and smoking. Fractional polynomial models were fitted to evaluate longitudinal trends in TC before death or end-of-study. Adjusted odds ratios were estimated using generalised estimating equations. Results: There were 63,630 women and 36,128 men, mean age 86 years, with 29,200 deaths. There were 41,164 treated with statins at cohort entry. Compared with TC values of 4.5 to 5.4 mmol/L, TC values <3.0 mmol/L were associated with higher mortality (statin treated HR 1.53, 95% confidence interval 1.43 to 1.64, P<0.001; not treated, 1.41, 1.29 to 1.54, P<0.001). A secular decline in TC values accelerated in the last two years of life. In the last quarter of follow-up, the adjusted odds of TC<3.0 mmol/L for those who died, compared with surviving participants, were 3.33 (2.84 to 3.91, P<0.001) for untreated and 1.88 (1.68 to 2.11, P<0.001) for statin treated participants. Conclusions: TC values show a terminal decline in the last years of life. Reverse causation may contribute to the association of lower TC with higher mortality in non-randomized studies.