Causal Effect ofHelicobacter PyloriInfection on Coronary Heart Disease is mediated by Body Mass Index: A Mendelian Randomization Study

Abstract

AbstractBackgroundMore than half of the world’s population have been infected withH. pylori, however the relationship betweenH. pyloriinfection and coronary heart disease (CHD) is unknown.MethodsThis study used mendelian randomization (MR) analyses. The instrument variables forH. pyloriinfection were genetic variables (rs10004195 and rs368433) obtained from a published study. The outcome data included diagnosis, prognosis, and pathogenesis data for CHD, which were extracted from the public genome-wide association studies database, mainly from the CARDIoGRAMplusC4D consortium, UK Biobank, IEU database, and FinnGen database. MR analyses were performed per outcome database and were conducted by reverse analysis. Two step MR analyses were used to explore indirect pathogenic factors ofH. pyloriinfection.ResultsGenetically-predictedH. pyloriinfection was causally associated with body mass index (BMI) (β, 0.022; 95% CI, 0.008–0.036;p-value = 0.001), but not with the diagnosis of CHD (OR, 0.991; 95%CI, 0.904–1.078;p-value = 0.842, IEU database; OR, 1.049; 95% CI, 0.980–1.118;p-value = 0.178, FinnGen database) and prognosis of CHD (OR, 0.999; 95% CI, 0.997–1.001;p-value = 0.391, IEU database; OR, 1.022; 95% CI, 0.922–1.123;p-value = 0.663, FinnGen database). The causal effect ofH. pyloriinfection on CHD is mediated by BMI. Inverse MR showed no causal effect of CHD onH. pyloriinfection.ConclusionsOur findings confirm the causal effect ofH. pyloriinfection on CHD is mediated by BMI. Eradication or prevention ofH. pyloriinfection may have a clinical benefit for patients with CHD indirectly.Clinical PerspectiveWhat Is New?Genetically-predictedH. pyloriinfection was causally associated with body mass index, but not with the diagnosis and prognosis (major adverse cardiovascular events) of coronary heart disease.The causal effect ofH. pyloriinfection on coronary heart disease is mediated by body mass index. Inverse mendelian randomization analyses showed no causal effect of coronary heart disease onH. pyloriinfection.What Are the Clinical Implications?Our findings confirm that the causal effect of H. pylori infection on coronary heart disease is partially mediated by body mass index.Eradication or prevention of H. pylori infection may have a clinical benefit for patients with CHD indirectly.