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
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 conduc...
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Elsevier
2025-09-01
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| Series: | International Journal of Cardiology. Cardiovascular Risk and Prevention |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772487525001096 |
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| author | Weibo Zhang Hailing Zhang |
| author_facet | Weibo Zhang Hailing Zhang |
| author_sort | Weibo Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-76e318b3bac44c7897e3d51a3a258abd |
| institution | Kabale University |
| issn | 2772-4875 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Cardiology. Cardiovascular Risk and Prevention |
| spelling | doaj-art-76e318b3bac44c7897e3d51a3a258abd2025-08-24T05:15:25ZengElsevierInternational Journal of Cardiology. Cardiovascular Risk and Prevention2772-48752025-09-012620047110.1016/j.ijcrp.2025.200471Elevated serum glutathione peroxidase levels reducing the risk of acute upper gastrointestinal bleeding combined with acute coronary syndrome: Evidence from observational, interventional, and Mendelian randomization studiesWeibo Zhang0Hailing Zhang1Foshan Fosun Chancheng Hospital, Guangdong, 528031, ChinaCorresponding author.; Foshan Fosun Chancheng Hospital, Guangdong, 528031, ChinaBackground: 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.http://www.sciencedirect.com/science/article/pii/S2772487525001096Glutathione peroxidaseAcute upper gastrointestinal hemorrhageAcute coronary syndromeMendelian randomizationSelenium supplementation |
| spellingShingle | Weibo Zhang Hailing Zhang 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 International Journal of Cardiology. Cardiovascular Risk and Prevention Glutathione peroxidase Acute upper gastrointestinal hemorrhage Acute coronary syndrome Mendelian randomization Selenium supplementation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Glutathione peroxidase Acute upper gastrointestinal hemorrhage Acute coronary syndrome Mendelian randomization Selenium supplementation |
| url | http://www.sciencedirect.com/science/article/pii/S2772487525001096 |
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