Coronary artery disease is responsible for up to 17 million deaths worldwide each year19, while UA can lead to serious complications such as myocardial infarction and sudden cardiac death. Therefore, further understanding of risk factors for adverse outcomes in patients is needed. In this study, we investigated the clinical significance of serum Helicobacter pylori CagA antibody levels in UA patients. The results demonstrated important associations between serum Helicobacter pylori CagA antibody levels and clinical factors, severity, and prognosis in UA patients.
SYNTAX is a coronary angiography scoring system that reflects the complexity and burden of coronary artery disease (CAD). According to the 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization, the SYNTAX score can be used to assess the severity of coronary artery stenosis 20. Anatomical SYNTAX score has been proven to predict the occurrence rate of major adverse cardiac events (MACE) and long-term prognosis in stable CAD patients undergoing coronary artery revascularization 21. Xu et al. also demonstrated that a high SYNTAX score is an independent predictor for MACE in UA patients after medical treatment 22. In our study, we similarly found that SYNTAX score was a risk factor for adverse outcomes in UA patients. Furthermore, we observed that the CagA-positive group of UA patients had significantly higher SYNTAX scores compared to the CagA-negative group. This finding suggests that CagA positivity may be associated with more severe coronary artery disease and may indicate a higher risk of adverse cardiovascular events in these patients.
Additionally, we also found significant differences in lipid metabolism and inflammatory markers between the CagA-positive and CagA-negative groups. In other disease types, Yang et al. found that the CagA-IgG positive group had significantly higher levels of TC, TG, and LDLC compared to the CagA-IgG negative group 23. Huang et al. demonstrated that patients with coronary heart disease in the Helicobacter pylori CagA group had significantly elevated levels of total cholesterol, low-density lipoprotein, lipoprotein B, serum hsCRP, and oxLDL, as well as a significant increase in the severity of coronary artery atherosclerosis 24. In our study, we found that UA patients in the CagA-positive group had significantly higher levels of serum TC and hs-CRP compared to the CagA-negative group. However, there was no significant difference in LDLC levels between the two groups. In clinical practice, it is generally desired to have lower LDLC levels in UA patients 25. The discrepancy between our study and previous research findings could be attributed to variations in inclusion/exclusion criteria, sample size, different patient characteristics, and comorbidities. This suggests that further studies are needed to validate our findings. H. pylori has been shown to induce chronic low-grade inflammation, which can trigger a cascade of events leading to endothelial dysfunction, plaque instability, and thrombosis, ultimately contributing to the development of UA26. Mechanistically, Li et al. confirmed that CagA promotes plaque growth in early stages of atherosclerosis in apolipoprotein E-deficient mice and enhances the expression of adhesion molecules and inflammatory cytokines in mouse aortic endothelial cells (MAECs) 16. Our findings support previous research indicating an association between serum Helicobacter pylori CagA antibody positivity and lipid metabolism as well as inflammatory response.
In addition to the above associations, our study demonstrated a positive correlation between CagA antibody levels and SYNTAX scores. Higher CagA antibody levels were associated with more severe coronary artery disease, indicating a potential role of CagA antibodies as a biomarker for disease severity in UA patients. In other studies, CagA antibodies have also been used as biomarkers for certain diseases. For example, Shiota et al. demonstrated a positive correlation between the presence of anti-CagA antibodies and gastric cancer, suggesting that anti-CagA antibodies can serve as a biomarker for gastric cancer in East Asian countries 27. Lu et al. showed that CagA-positive expression is associated with the severity and prognosis of gastric adenocarcinoma, indicating that CagA expression could be a promising biomarker for metastasis and prognosis in gastric adenocarcinoma, as well as a potential therapeutic target 28. Moreover, we found that CagA antibody levels could predict the occurrence of major adverse cardiovascular events (MACE) within one year in UA patients. This highlights the potential utility of CagA antibody levels as a prognostic indicator for UA patients. These findings underline the importance of considering CagA antibody levels alongside traditional risk factors for risk stratification and management of UA patients.
There are several limitations to this study. Firstly, it is a single-center study with a relatively small sample size, which may limit the generalizability of the findings. Secondly, we only measured a subset of clinical factors and serum markers. Thirdly, the specific mechanisms underlying the association between CagA positivity and UA could not be determined in this study. Further clinical and basic research is needed to confirm our findings and investigate the underlying mechanisms.