Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study. Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40–69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline. With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80–1.24) for men and 0.80 (0.65–0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285). Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.

中文翻译：

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社区居住成年人血清总胆红素与代谢综合征发生风险之间关系的性别差异：使用 16 年以上纵向队列数据进行倾向评分分析

关于代谢综合征 (MetS) 可识别风险的研究正在进行中，越来越多的证据表明胆红素是一种有效的抗氧化剂和针对 MetS 的细胞保护剂。然而，关于胆红素和 MetS 之间的关系存在相互矛盾的结果。我们的研究旨在通过纵向前瞻性研究中对男性和女性的数据进行单独分层来验证这种关联。数据来自韩国疾病控制和预防中心提供的韩国基因组流行病学研究。对 5,185 名 40-69 岁成年人（3,089 名男性和 2,096 名女性）未接受 MetS 的数据进行了分析。参与者根据血清总胆红素水平的性别特异性四分位数进行分组，并每两年进行一次随访，为期 16 年（直到 2018 年）。采用对数秩检验根据性别特异性血清总胆红素四分位数获得 MetS 累积发生率的 Kaplan-Meier 曲线，并分析代谢综合征事件的风险比 (HR) 和 95% 置信区间 (CI)在倾向评分匹配消除基线差异后，使用多重 Cox 比例风险回归分析模型。随着血清总胆红素四分位数的增加，男性和女性每 1000 人年的发病率成比例下降。经过倾向评分匹配并调整混杂变量后，最高四分位数相对于最低四分位数的 MetS 的 HR（95% CI）男性为 1.00（0.80-1.24），女性为 0.80（0.65-0.99）。血清总胆红素的较高四分位显示女性中 MetS 的累积发生率显着较低（对数秩检验 p = 0.009），但在男性中则不然（对数秩检验 p = 0.285）。女性血清总胆红素水平与 MetS 显着负相关，但在男性中没有观察到显着相关性。在临床环境中按性别预测 MetS 事件时，应注意血清总胆红素影响的性别差异。