Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Jinhua Wenrong Hospital, Jinhua, People's Republic of China.
Sci Rep. 2024 Sep 3;14(1):20451. doi: 10.1038/s41598-024-71497-x.
Bilirubin is widely recognized to possess antioxidant and anti-inflammatory characteristics. However, the relationship between bilirubin and coronary artery disease (CAD) remains controversial, particularly in individuals receiving Percutaneous Coronary Intervention (PCI). Given that statins may enhance the production of heme oxygenase-1 (HO-1) and bilirubin, we investigated the long-term cardiovascular prognostic role of bilirubin levels elevated by statin use in patients undergoing PCI. Data of 6945 subjects undergoing PCI were enrolled in this study. We divided the patients into two groups based on serum total bilirubin (TB) levels detected prior to PCI. The high TB group consisted of patients with serum TB values > 8.4 μmmol/L, while the low TB group consisted of patients with serum TB values ≤ 8.4 μmmol/L. The median follow-up time was 836 days. Cox proportional hazards models were performed to evaluate the hazard ratios (HRs) and 95% confidence interval (CI) for the incidence of major adverse cardiovascular event (MACE) associated with bilirubin levels. The association between TB levels and risk of MACE was significant [adjusted HR = 0.557, 95% CI (0.59-0.96), p = 0.020). Linear analysis was performed to determine the association between preadmission usage of statin and bilirubin level. The preadmission usage of statin independently linearly increases TB [adjusted-β = 0.371, 95% CI (0.134-0.608), p = 0.002] and direct bilirubin (DB) [adjusted-β = 0.411, 95% CI (0.300-0.522), p < 0.001). Mediation analysis demonstrated a direct protective role of preadmission statins treatment (β = - 0.024, p < 0.01), TB (β = - 0.003, p < 0.05) and DB (β = - 0.009, p < 0.05). Furthermore, it was found that TB (4.0%) and DB (12.0%) mediated the relationship between preadmission statins therapy and MACE. Bilirubin has a protective effect against MACE. In patients with normal bilirubin level undergoing elective PCI, preadmission statin use elevated bilirubin levels, which were independently associated with a lower incidence of MACE over the long-term follow-up period.
胆红素被广泛认为具有抗氧化和抗炎特性。然而，胆红素与冠状动脉疾病（CAD）之间的关系仍存在争议，尤其是在接受经皮冠状动脉介入治疗（PCI）的患者中。鉴于他汀类药物可能增强血红素加氧酶-1（HO-1）和胆红素的产生，我们研究了他汀类药物使用引起的胆红素水平升高对接受 PCI 的患者的长期心血管预后的作用。本研究纳入了 6945 例接受 PCI 的患者的数据。我们根据 PCI 前检测的血清总胆红素（TB）水平将患者分为两组。高 TB 组包括血清 TB 值>8.4μmmol/L 的患者，低 TB 组包括血清 TB 值≤8.4μmmol/L 的患者。中位随访时间为 836 天。使用 Cox 比例风险模型评估胆红素水平与主要不良心血管事件（MACE）发生率相关的危险比（HR）和 95%置信区间（CI）。TB 水平与 MACE 风险之间存在显著关联[校正 HR=0.557，95%CI（0.59-0.96），p=0.020]。进行线性分析以确定入院前使用他汀类药物与胆红素水平之间的关联。入院前使用他汀类药物独立地呈线性增加 TB[校正-β=0.371，95%CI（0.134-0.608），p=0.002]和直接胆红素（DB）[校正-β=0.411，95%CI（0.300-0.522），p<0.001]。中介分析表明入院前他汀类药物治疗（β=-0.024，p<0.01）、TB（β=-0.003，p<0.05）和 DB（β=-0.009，p<0.05）具有直接保护作用。此外，发现 TB（4.0%）和 DB（12.0%）介导了入院前他汀类药物治疗与 MACE 之间的关系。胆红素对 MACE 有保护作用。在接受择期 PCI 的胆红素水平正常的患者中，入院前使用他汀类药物可升高胆红素水平，且与长期随访期间 MACE 发生率降低独立相关。
