Abstract 4658: Association of serum retinol with risk of overall and cause-specific mortality: A 30-year prospective cohort study

Abstract

Abstract Retinoic acid, an active metabolite of retinol, has been associated with increased overall and cardiovascular mortality. However, the association between retinol, the most biologically active vitamin A metabolite, and long-term mortality is unexplored. The objective of this study is to determine whether serum retinol is associated with overall and cause-specific mortality, and to elucidate the dose-response characteristics of the association. We conducted a prospective serological analysis of 29,104 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. Serum retinol was assayed at baseline using high-performance liquid chromatography, and multivariable-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and their two-sided 95% confidence intervals (CIs). During a 30-year follow-up through linkage with Finnish Causes of Death Registry, there were 23,797 deaths, including from cardiovascular disease (9,869), cancer (7,695), respiratory disease (2,161), diabetes mellitus (119), injuries and accidents (1,255), and other causes (2698). In the multivariable-adjusted model, participants with higher serum retinol experienced significantly lower overall mortality compared to men with the lowest concentrations (HRs=0.87, 0.84, 0.80 and 0.83 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001). After excluding the first 5 years of follow-up following blood collection, the associations were generally similar, with higher serum retinol being significantly associated with reduced overall mortality, as well as mortality from cardiovascular disease, heart disease, respiratory disease and other causes (reductions of risk from 15% to 32% for the highest versus lowest retinol quintiles). By contrast, the serum retinol associations with cancer and stroke mortality were not significant after excluding the first 5 years (HRs=0.91 and 0.89, Q5 versus Q1; Ptrend=0.09 and 0.21, respectively). The retinol-total mortality association was similar across subgroups of age, smoking intensity and duration, BMI, trial supplementation and duration of follow-up, but was modified by alcohol consumption, with a stronger inverse association among men who drank more (≥20.4 g/day; HRs= 0.82. 0.75, 0.74. 0.74, Q2-Q5 versus Q1, respectively; Pinteraction=0.002). In this large prospective cohort analysis, high serum retinol is associated with lower overall mortality, including deaths from cardiovascular disease, heart disease, respiratory disease and other causes. Our data provide evidence of the importance of vitamin A biochemical status for long-term health. Citation Format: Jiaqi Huang, Stephanie J. Weinstein, Kai Yu, Demetrius Albanes. Association of serum retinol with risk of overall and cause-specific mortality: A 30-year prospective cohort study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4658.