a Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
b Department of Cardiology and Epidemiology, Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine , Shiyan , China.
Ann Med. 2018 Feb;50(1):16-25. doi: 10.1080/07853890.2017.1377846. Epub 2017 Sep 18.
Total bilirubin (TBIL) is known to be inversely associated with coronary heart disease (CHD) risk, however, whether this association is dose-response remains inconsistent and it is unclear which subtype of bilirubin is responsible for the potential protective effect.
We included 12,097 participants who were free of CHD, stroke, cancer and potential liver, biliary and renal diseases at baseline from September 2008 to June 2010 and were followed-up until October 2013. Cox proportional hazards models were used to assess the hazard ratios (HR) and 95% confidence interval (95% CI) of bilirubin with incident CHD risk.
The adjusted HRs for incident CHD increased with increasing direct bilirubin (DBIL) (p for trend = .013). Participants within the highest quintile of DBIL had 30% higher risk of incident CHD compared to those in the lowest quintile (95% CI: 1.07, 1.58). In contrast, compared with subjects in the lowest quintile of TBIL, those in the third quintile had the lowest of 24% risk for CHD incidence (95% CI: 0.63, 0.92), which showed a U-shaped association (p for quadratic trend = .040).
DBIL was associated with a dose-response increased risk for CHD incidence. However, a U-shaped association existed between TBIL, indirect bilirubin and incident CHD risk. Key messages Direct bilirubin is independently associated with incident coronary heart disease (CHD) in a dose-response manner. A similarly consistent U-shaped association was found between total bilirubin, indirect bilirubin and incident CHD. The potential protective effect of total bilirubin within the normal range on incident CHD should be mainly attributed to mild-to moderate elevated levels of indirect bilirubin.
总胆红素（TBIL）与冠心病（CHD）风险呈负相关，但这种关联是否呈剂量反应关系尚不一致，也不清楚哪种胆红素亚型对潜在的保护作用负责。
我们纳入了 12097 名参与者，他们在 2008 年 9 月至 2010 年 6 月基线时无 CHD、中风、癌症以及潜在的肝、胆道和肾脏疾病，并随访至 2013 年 10 月。使用 Cox 比例风险模型评估胆红素与 CHD 发病风险的风险比（HR）和 95%置信区间（95%CI）。
随着直接胆红素（DBIL）的增加，CHD 发病的调整后 HR 增加（趋势 P 值=0.013）。与 DBIL 最低五分位的参与者相比，DBIL 最高五分位的参与者 CHD 发病风险增加 30%（95%CI：1.07，1.58）。相比之下，与 TBIL 最低五分位的受试者相比，TBIL 第三五分位的受试者 CHD 发病风险最低，为 24%（95%CI：0.63，0.92），呈 U 形关联（二次趋势 P 值=0.040）。
DBIL 与 CHD 发病风险呈剂量反应关系。然而，TBIL、间接胆红素与 CHD 发病风险之间存在类似的一致性 U 形关联。总胆红素在正常范围内对 CHD 发病的潜在保护作用主要归因于间接胆红素的轻度至中度升高。
