ArticleInternational journal of cardiology. Cardiovascular risk and prevention2025
Elevated serum glutathione peroxidase levels reducing the risk of acute upper gastrointestinal bleeding combined with acute coronary syndrome: Evidence from observational, interventional, and Mendelian randomization studies.
Article in International journal of cardiology. Cardiovascular risk and prevention, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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. Results: 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). Conclusion: 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.
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