Body mass index found to mediate causal associations between Helicobacter pylori infections and coronary artery disease risk

By Pooja Toshniwal PahariaJan 23 2024Reviewed by Lily Ramsey, LLM

In a recent study published in Scientific Reports, researchers used the bidirectional Mendelian randomization (MR) method, using Helicobacter pylori infection as the study exposure, to investigate its causal relationship with coronary heart disease (CHD) diagnosis, prognosis, and potential pathogenesis.

Study: The causal effect of Helicobacter pylori infection on coronary heart disease is mediated by the body mass index: a Mendelian randomization study. Image Credit: K_E_N/Shutterstock.com

Background

H. pylori, a gram-negative bacterium, affects the stomach and duodenum and can cause systemic reactions such as abnormal glucose and lipid metabolism, blood hypercoagulability, chronic inflammatory reactions, and vitamin deficiency.

Helicobacter pylori is a leading cause of mortality in several nations; however, the association between Helicobacter pylori infection and coronary artery disease is unclear. Eradication therapy can reduce peripheral blood inflammatory cytokines associated with atherosclerosis and CHD development.

Further research is required to determine the causal association and whether routine H pylori screening and treatment can prevent and treat CHD.

About the study

In the present study, researchers used Helicobacter pylori infections as exposure and pathogenesis as the outcome for the bidirectional Mendelian randomization analysis to infer the associations between Helicobacter pylori infection and CHD diagnosis, pathogenesis, and prognosis.

They also explored the reverse causal association between coronary heart disease and Helicobacter pylori infection by two-step Mendelian randomization.

The researchers derived the genetic associations of coronary heart disease from CARDIoGRAMplusC4D Consortium data, including 60,801 case individuals and 123,504 controls from 48 research studies.

They used the FinnGen database to derive summary statistical information for coronary heart disease, angina pectoris, and myocardial infarction (MI) and the European Bioinformatics Institute (EBI) database to derive Helicobacter pylori infection data.

The team collected genome-wide association studies (GWAS) data to investigate causal effects between Helicobacter pylori infections and coronary heart disease, including heart arrhythmia, major-type adverse cardiovascular events (MACE), heart failure, stroke, heart attack, maximum heart rate (HR) during fitness test, and target HR attained data.

They used the MRC Integrated Epidemiology Unit (MRC-IEC) database to obtain vitamin data, the publicly accessible IEU database for inflammation data, and the United Kingdom Biobank (UKBB) database for lipid data.

The researchers determined the demographic features of genome-wide association studies data for Helicobacter pylori infection (pregnant females living in Avon, with expected dates of delivery between 1 April 1991 and 31 December 1992) and measured serological titers of antibodies associated with Helicobacter pylori infection using enzyme-linked immunosorbent assays (ELISA).

They acquired genetic IVs from previous literature and used them in the Mendelian randomization analysis of Helicobacter pylori infections and the non-alcoholic type of fatty liver disease (NAFLD).

The single-nucleotide polymorphisms (SNPs) rs10004195 and rs368433, present in the Fc gamma RIIA (FCGR2A) gene (at the 1q23.3 position) and Toll-like receptor 10 (TLR10) gene (at the 4p14 position), respectively, known to have strong associations with Helicobacter pylori infections, were used as instrumental variables (IVs) for analysis.

The team identified pathogenic mechanisms of Helicobacter pylori infections in CHD, including abnormal glucose and lipid metabolism, vitamin deficiency, and chronic inflammatory reactions.

They also analyzed whether Helicobacter pylori infections contributed to the occurrence of CHD through inflammatory mechanisms.

They identified the instrumental variables of CHD, MI, and angina pectoris from public GWAS summary data using three MR analysis methods: inverse variance-weighted (IVW), weighted median, and MR-Egger.

Results

Helicobacter pylori infections were associated with increased body mass index (BMI), a significant factor in CHD incidence. The infection's mechanism may be through the brain-gut axis, altering appetite and promoting energy intake, leading to increased BMI.  

The odds ratio (OR) for Helicobacter pylori infection was 1.0, with an IEU database showing an OR of 1.05 and FinnGen indicating an OR of 1.0. There were neither causal effects of CHD on Helicobacter pylori infections nor associations between Helicobacter pylori infections and CHD occurrence, angina pectoris, or MI.

In addition, H. pylori infection showed no causal effects on MACE, heart arrhythmia, heart attack, stroke, heart failure, target HR achieved, or maximum HR.

The study found no association between Helicobacter pylori infections and abnormal glucose and lipid metabolism, triglyceride levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) levels.

The team also found negative results for water-soluble vitamin B12 and vitamin C and B12 and fat-soluble vitamin D and no causal relationships between Helicobacter pylori infections and interleukins (IL)-4,6, 8, 10, 18, or tumor necrosis factor-alpha (TNF-α).

Conclusions

Overall, the study findings showed that BMI mediates the causal effects of Helicobacter pylori infections on CHD incidence; therefore, eradicating or preventing H. pylori infection may indirectly benefit CHD patients.

Study limitations include using serological samples for analysis, which might not truly represent Helicobacter pylori infections, and sample selection from European ancestry and, therefore, a lack of generalizability of the study findings. Stringent screening of instrumental variables might have also led to negative results.