Background and aims: Bilirubin, a breakdown product of heme metabolism, has been shown to be protective against cardiovascular mortality; however, it is also a marker of liver function. There are limited data on the longitudinal changes in bilirubin with aging in a population-based cohort of older adults. This study was designed to determine whether serum bilirubin changes with age in older adults, and to evaluate whether age attenuates the association between bilirubin and mortality.
Methods: This is a prospective cohort study of 2364 participants with a mean age of 70 years, who completed a research clinic visit from 1984 to 1987, and 1703 participants who returned for a second research visit approximately 8 years later. Cross-sectional and longitudinal multivariable-adjusted analyses were performed to examine the association between serum bilirubin, aging, and mortality.
Results: In cross-sectional analyses, when the cohort was divided into quartiles of age, higher baseline serum bilirubin levels were associated with older age in analyses adjusted for sex, body mass index (BMI), alanine aminotransferase (ALT), albumin, and metabolic traits (P-value <0.001). In longitudinal analyses, among the subset of participants who had two research visits, aging remained significantly associated with an increase in bilirubin in multivariable-adjusted models (P-value <0.0001). When the longitudinal cohort was divided into bilirubin quartiles, Kaplan-Meier analysis showed an incremental reduction in survival with higher bilirubin levels (P-value = 0.002); however, this association between bilirubin quartile and mortality was no longer significant after adjusting for age (P-value 0.30), suggesting higher bilirubin in older age does not confer survival advantage.
Conclusions: Serum bilirubin levels gradually increase with age in older adults. Elevated bilirubin in older individuals is not associated with improved survival as previously reported in middle-aged populations.
Keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma glutamyl transpeptidase; LDL, low-density lipoprotein; MELD, model for end stage liver disease; MRP2, multi drug resistance protein 2; UGT, uridine diphosphate-glucuronosyltransferase; aging; bilirubin; liver; mortality.