Zhang Weibo, Zhang Hailing
Foshan Fosun Chancheng Hospital, Guangdong, 528031, China.
Int J Cardiol Cardiovasc Risk Prev. 2025 Jul 15;26:200471. doi: 10.1016/j.ijcrp.2025.200471. eCollection 2025 Sep.
Acute upper gastrointestinal hemorrhage (UGIH) combined with acute coronary syndrome (ACS) poses a significant clinical challenge linked to oxidative stress, while elevated serum glutathione peroxidase (GSH-Px) levels may provide a protective effect.
A two-phase study was conducted. First, Mendelian randomization (MR) analysis using three GSH-Px-associated SNPs (rs6993770, rs1097234, rs4149991) was performed to assess causality between genetically predicted GSH-Px activity and UGIH-ACS risk, leveraging public GWAS data. Second, a randomized, double-blind, placebo-controlled trial (RCT) enrolled UGIH-ACS patients (n = 110) to received oral selenium (200 μg/day) or placebo for 8 weeks. Comparisons were made with a UGIH-only control group (n = 78) and healthy controls (n = 83). Serum GSH-Px levels, 90-day mortality, rebleeding rates, and major adverse cardiovascular events (MACE) were analyzed.
MR analysis showed no significant causal link between GSH-Px activity and UGIH-ACS risk (IVW OR: 0.966, 95 % CI: 0.873-1.069, p = 0.502), but the weighted median method suggested a marginal protective trend (OR: 0.958, 95 % CI: 0.918-1.000, p = 0.048). Sensitivity analyses confirmed robust estimates with low heterogeneity. In the RCT, selenium supplementation significantly increased GSH-Px levels (+51.9 % vs. +6.0 %, p < 0.001), reduced 90-day rebleeding (12.0 % vs. 22.7 %, p = 0.014), and lowered MACE risk (9.1 % vs. 21.8 %, p = 0.042).
While MR analysis found no strong causal link between GSH-Px activity and UGIH-ACS risk, the weighted median method indicated a marginal protective trend, underscoring GSH-Px's role in oxidative stress modulation. Selenium supplementation significantly increased GSH-Px activity (+51.9 %, p < 0.001), reduced rebleeding, and lowered MACE risk, supporting its potential as adjunctive therapy for UGIH-ACS and warranting further investigation into additional mechanisms.
急性上消化道出血（UGIH）合并急性冠状动脉综合征（ACS）是一个与氧化应激相关的重大临床挑战，而血清谷胱甘肽过氧化物酶（GSH-Px）水平升高可能具有保护作用。
进行了一项两阶段研究。首先，利用公开的全基因组关联研究（GWAS）数据，使用三个与GSH-Px相关的单核苷酸多态性（SNP）（rs6993770、rs1097234、rs4149991）进行孟德尔随机化（MR）分析，以评估基因预测的GSH-Px活性与UGIH-ACS风险之间的因果关系。其次，一项随机、双盲、安慰剂对照试验（RCT）纳入了UGIH-ACS患者（n = 110），给予口服硒（200μg/天）或安慰剂，持续8周。与仅患有UGIH的对照组（n = 78）和健康对照组（n = 83）进行比较。分析血清GSH-Px水平、90天死亡率、再出血率和主要不良心血管事件（MACE）。
MR分析显示GSH-Px活性与UGIH-ACS风险之间无显著因果关系（逆方差加权法比值比：0.966，95%置信区间：0.873-1.069，p = 0.502），但加权中位数法显示出微弱的保护趋势（比值比：0.958，95%置信区间：0.918-1.000，p = 0.048）。敏感性分析证实了具有低异质性的稳健估计。在RCT中，补充硒显著提高了GSH-Px水平（+51.9%对+6.0%，p < 0.001），降低了90天再出血率（12.0%对22.7%，p = 0.014），并降低了MACE风险（9.1%对21.8%，p = 0.042）。
虽然MR分析未发现GSH-Px活性与UGIH-ACS风险之间有强烈的因果关系，但加权中位数法显示出微弱的保护趋势，强调了GSH-Px在氧化应激调节中的作用。补充硒显著提高了GSH-Px活性（+51.9%，p < 0.001），降低了再出血率，并降低了MACE风险，支持其作为UGIH-ACS辅助治疗的潜力，并需要进一步研究其他机制。
