The role of helicobacter pylori in coronary heart disease : laboratory, observational, and interventional studies

<p dir="ltr"><b>Background</b></p><p dir="ltr">Helicobacter pylori (H. pylori) infects nearly half of the world's population and causes gastritis, peptic ulcers, and malignancy. It has also been associated with atherosclerosis and coronary heart disease (CHD). Moreover, infection with H. pylori may complicate treatment in patients with established CHD taking antithrombotic therapy by increasing the risk of upper gastrointestinal bleeding. The link between H. pylori infection and CHD remains unclear, and there are no large randomised trial data on the effects of eradicating H. pylori in patients with CHD on gastrointestinal bleeding and cardiovascular outcomes.</p><p dir="ltr"><b>Methods and results </b></p><p dir="ltr"><b>Study I</b>: Coronary artery smooth muscle cells from three donors were co-cultured with recombinant fragmented CagA protein. Effects on inflammation and calcification were evaluated using qPCR, ELISA, and a calcification assay. CagA induced a pro-inflammatory response by upregulating inflammatory cytokines and COX-2. It also increased BMP2 expression, a key regulator of calcification, and promoted cell calcification in a calcification assay.</p><p dir="ltr"><b>Study II</b>: A prospective nested case-control study that assessed the association between H. pylori serology and incident MI in 826 health examination participants and matched controls, incorporating CagA status, temporal trends, and national registry-derived data on socioeconomic status. No significant association between H. pylori- or CagA seropositivity and incident MI was found (odds ratio 1.15, 95% CI 0.94-1.42).</p><p dir="ltr"><b>Study III</b>: A prospective biomarker study in 1061 patients with MI that investigated the association between H. pylori, CagA serology and cardiovascular and inflammatory biomarkers. Preselected biomarkers were analysed, followed by an exploratory analysis incorporating all 175 biomarkers. Associations between H. pylori status, the top biomarker predictors, and post-MI outcomes were assessed. Patients with H. pylori infection had higher CRP concentrations, with higher levels in those who were also CagA-positive. Biomarkers moderately predicted H. pylori status, and three inflammatory biomarkers were the strongest predictors. Two of the biomarker predictors, but not H. pylori independently, were associated with MACE and all-cause mortality.</p><p dir="ltr"><b>Study IV</b>: A cluster randomised crossover clinical trial with registry-based data collection in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) designed to determine if routine H. pylori screening reduces the incidence of upper gastrointestinal bleeding (UGIB) in patients with MI, and secondarily to assess effects on cardiovascular outcomes and mortality. In total, 35 Swedish hospitals were cluster-randomised to either routine H. pylori screening of patients with type-1 MI using the urea breath test or usual care for one year, followed by a crossover to the alternate allocation for another year. A total of 18 466 patients were followed up. During screening periods, 6 480 patients (70%) underwent testing, of whom 1 532 (23.6%) tested positive for H. pylori. After a median follow-up of 1.9 years, 299 patients in the screening group and 336 in the usual care group experienced UGIB (rate ratio 0.90, 95% CI 0.77-1.05). Subgroup analyses suggested heterogeneity in treatment effect, with a screening benefit among patients with anaemia and chronic kidney disease.</p><p dir="ltr"><b>Conclusions</b></p><p dir="ltr">Prospective data did not demonstrate a strong association between H. pylori and incident MI, although a small effect cannot be excluded. CagA induces pro- inflammatory and pro-calcific responses in CASMCs. In patients with MI, H. pylori, particularly with CagA-positivity, was associated with higher systemic inflammation, reflected by elevated CRP levels. Inflammatory markers also emerged as predictors of H. pylori status. Routine screening for H. pylori with the urea breath test in a Swedish MI population did not reduce UGIB or improve outcomes, but targeted screening and eradication in patients at high bleeding risk may represent a clinically relevant strategy to reduce UGIB.</p><h3 dir="ltr">List of scientific papers</h3><p dir="ltr">I. Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells <b>Martin O Sundqvist</b>, Jonatan Wärme, Robin Hofmann, Sven- Christian Pawelzik, Magnus Bäck International Journal of Molecular Sciences 2023 Mar 11;24(6):5392 <a href="https://doi.org/10.3390/ijms24065392" rel="noreferrer" target="_blank">https://doi.org/10.3390/ijms24065392</a></p><p dir="ltr">II. Seroprevalence of Helicobacter pylori and incident myocardial infarction - A population-based Swedish nested case-control study <b>Martin O Sundqvist</b>, Per Svensson, Stefan Söderberg, Ingvar A Bergdahl, Patrik Wennberg, Per Tornvall, Jonas S O Andersson, Robin Hofmann International Journal of Cardiology 2025 Feb 15:421:132917 <a href="https://doi.org/10.1016/j.ijcard.2024.132917" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.ijcard.2024.132917</a></p><p dir="ltr">III. Helicobacter pylori, Inflammation and Long-term Outcome in Patients with Acute Myocardial Infarction <b>Martin O Sundqvist</b>, Jonatan Wärme, Marcus Hjort, Per Tornvall, Tomas Jernberg, Bertil Lindahl, Alexandru Schiopu, Tomasz Baron, Stefan H Jacobson, Thomas Kahan, David Erlinge, Jonas Spaak, Robin Hofmann Helicobacter 2026 Mar-Apr;31(2):e70116 <a href="https://doi.org/10.1111/hel.70116" rel="noreferrer" target="_blank">https://doi.org/10.1111/hel.70116</a></p><p dir="ltr">IV. Helicobacter pylori Screening After Acute Myocardial Infarction The Cluster Randomized Crossover HELP-MI SWEDEHEART Trial Robin Hofmann, Stefan James, <b>Martin O. Sundqvist</b>, Jonatan Wärme, Oskar Angerås, Joakim Alfredsson, David Erlinge, Gabriel Arefalk, Göran Arstad, Simon Blomberg, Ole Fröbert, Kristina Hambraeus, Per M. Hellström, Jörg Lauermann, Matthias Lidin, Lars Lindhagen, Georgios Mourtzinis, Carolina Schoede, Erik Thunström, Birgitta Voldberg, Henrik Wagner, Ollie Östlund, Tomas Jernberg, Magnus Bäck JAMA 2025;334;(13):1160-1169 <a href="https://doi.org/10.1001/jama.2025.15047" rel="noreferrer" target="_blank">https://doi.org/10.1001/jama.2025.15047</a></p>