Background: Hypercholesterolemia is a well-established risk factor for coronary heart disease, but the association between cholesterol level change and mortality is not fully understood. We aimed to investigate the association of 2 year (2002-2003 to 2004-2005) change in cholesterol with all-cause and cause-specific mortality in a population-based cohort study.
Methods and findings: The study population consisted of 269,391 participants aged more than 40 years who were free of myocardial infarction, stroke and cancer using the Korean National Health Insurance Service-National Health Screening Cohort. Cholesterol levels were classified into 1st, 2nd and 3rd tertiles during each of the first and second health examinations, respectively. The participants were followed-up for all-cause and cause-specific mortality from 1 January 2006 to 31 December 2013. Compared to participants who stayed within the 2nd tertile group for cholesterol during both the first and second examinations, participants who became or maintained cholesterol levels to the 1st tertile during the second examination had increased risk of all-cause mortality [adjusted hazard ratio (aHR) with 95% confidence interval (95% CI) = 1.28 (1.18-1.38) in 1st/1st, 1.16 (1.07-1.26) in 2nd/1st and 1.47 (1.32-1.64) in 3rd/1st tertile levels, respectively]. In addition, increased or persistent high cholesterol levels to the 3rd tertile was associated with elevated risk for all-cause mortality [aHR (95% CI) = 1.10 (1.01-1.20) in 1st/2nd, 1.16(1.03-1.31) in 1st/3rd and 1.15(1.05-1.25) in 3rd/3rd tertile levels].
Conclusions: Changes in cholesterol levels in either direction to low cholesterol or persistently low cholesterol levels were associated with higher risk of mortality. Particularly, spontaneous decline in cholesterol levels may be a marker for worsening health conditions.