REVIEW ARTICLE A Meta-Analysis of the Association between Helicobacter pylori Infection and Risk of Coronary Heart Disease from Published Prospective Studies Jing Sun, Pooja Rangan, Srinidhi Subraya Bhat and Longjian Liu Department of Epidemiology and Biostatistics, School of Public Health, Drexel University, Nesbitt Hall, 3215 Market St., Philadelphia, PA 19104, USA Keywords Meta-analysis, Helicobacter pylori, cardio- vascular risk factor. Reprint requests to: Longjian Liu, Department of Epidemiology and Biostatistics, School of Public Health, Drexel University, Nesbitt Hall, 3215 Market St., Philadelphia, PA 19104, USA. E-mail: Longjian.Liu@Drexel.edu Abstract Background: The association between helicobacter pylori (Hp) infection and coronary heart disease (CHD) has long been debated, and the results from previous meta-analysis are varied. Aims: The aim for this study was to identify the association between Hp and CHD using published perspective cohort studies. Materials and Methods: A systematic review and meta-analysis were per- formed on studies published from January, 1992 to April, 2014. All studies included used data from prospective cohort studies of CHD events or CHD deaths. Random effect models were applied in all estimations. Results: H. pylori infection increased the risk of CHD events by 11% (19 studies, n = 22,207, risk ratio (RR) = 1.11, 95% confidence interval (CI): 1.01–1.22). This effect was greater for studies that had less than 5 years’ fol- low-up time (RR = 1.15, 95% CI: 1.00–1.32). However, this effect was not significant for studies that had follow-up times ≥10 years (n = 5100, RR = 1.04, 95% CI: 0.87–1.24). Neither Cag-A seropositive nor Cag-A sero- negative strains of H. pylori were associated with a significantly increased risk of CHD events or deaths based on the current published data. Conclusion: In conclusion, H. pylori infection increased the risk of CHD events, especially in a patient’s early life, but this association was weaker or might be masked by other CHD risk factors in long-term observations. Atherosclerosis is the primary cause of coronary heart dis- ease (CHD), although other factors could play a role in the development of the disease [1]. Previous studies have suggested that some microorganisms and viral infections, including Helicobacter pylori, chlamydia pneumonia, and cytomegalovirus, also contribute to the development of CHD or have been identified as stimuli contributing to ischemic events [2–5]. Helicobacter pylori (H. pylori) infec- tion has long been associated with gastroduodenal lesions, and such chronic inflammation may trigger an immune response. In previous studies, anti-H. pylori immunoglob- ulin G (IgG) had been associated with an increased risk of CHD [6,7]. Several studies have also observed that CHD patients with H. pylori infection also have a higher preva- lence of positive cytotoxin-associated gene-A (Cag-A) antibodies [8,9]. Cag-A-positive H. pylori is a subtype of H. pylori that has been long associated with higher risk of gastric cancer and greater potential to stimulate immune responses compared to the other subtypes. Although the evidence from several studies has shown a positive association between H. pylori infection and CHD, others have indicated that the association is insignificant or only due to confounding effects [10– 12]. Several previous meta-analyses [13–15] also have provided evidence supporting or opposing the potential association between H. pylori infection and CHD events. Theses controversial results leave the H. pylori – CHD association studies under debate for years. In this study, we aimed to extend previous studies by examining the associations of H. pylori infection and Cag-A strains of H. pylori infection with the risk of CHD using a standard systematic review and meta-analysis © 2015 John Wiley & Sons Ltd, Helicobacter 21: 11–23 11 Helicobacter ISSN 1523-5378 doi: 10.1111/hel.12234