Analysis of Repeated Measurements of Serum Carotenoid Levels and All-Cause and Cause-Specific Mortality in Japan

IMPORTANCE The associations of levels of diverse serum carotenoids ascertained via repeated measurements with all-cause, cancer, and cardiovascular disease (CVD) mortality risk have not been considered in previous prospective studies. OBJECTIVE To investigate the association between repeated measurement of serum carotenoid levels and all-cause and cause-specific mortality risk. DESIGN, SETTING, AND PARTICIPANTS This cohort study's baseline data were collected using information from physical examinations from 1990 to 1999. Eligible participants were followed up until December 2017, with a median (interquartile range) follow-up period of 22.3 (15.5-25.3) years. Included individuals were age 40 years or older at the baseline data collection, were residents of the study site in the town of Yakumo, Hokkaido, Japan, and participated in a physical examination at least once from 1990 to 1999. Among eligible participants, after excluding 332 individuals, 3116 individuals were included in the analysis. Data analysis was conducted in April 2020. EXPOSURES Repeated measurements of 6 serum carotenoid levels and 4 associated indices. MAIN OUTCOMES AND MEASURES All-cause, cancer, and CVD mortality, categorized by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, were recorded. A time-dependent Cox regression model was performed to examine associations between time-varying serum carotenoid levels and mortality. RESULTS Among 3116 individuals who received physical examinations, the mean (SD) age was 54.7 (10.6) years and 1883 (60.4%) were women. During the follow-up period, 762 deaths from all causes, 253 deaths from cancer, and 210 deaths from CVD were ascertained. In a time-dependent Cox regression analysis, for every 25% higher serum levels of total carotenoids, risks were statistically significantly lower for all-cause mortality (hazard ratio [HR], 0.85; 95% CI, 0.82-0.87; P < .001), cancer mortality (HR, 0.82; 95% CI, 0.78-0.87; P < .001), and CVD mortality (HR, 0.86; 95% CI, 0.81-0.91; P < .001). Using only baseline measures, for every 25% higher serum levels of total carotenoids, risks were also statistically significantly lower for all-cause mortality (HR, 0.92; 95% CI, 0.89-0.95; P < .001), cancer mortality (HR, 0.87; 95% CI, 0.83-0.93; P < .001), and CVD mortality (HR, 0.93; 95% CI, 0.88-0.99; P = .03) but with larger HRs than those associated with repeated measurements. CONCLUSIONS AND RELEVANCE This study found that higher levels of serum carotenoids in analysis using repeated measurements were associated with significantly lower all-cause and cause-specific mortality over a follow-up period of 25 years.