Gut microbiota, immune cell traits, and major adverse cardiac events

As one of the primary composite endpoints in cardiovascular clinical research, major adverse cardiac events (MACE) are associated with poor clinical outcomes in patients with cardiovascular diseases. Gut microbiota and immune cells are increasingly recognized to be associated with MACE. However, the precise mechanisms remain unclear. We retrospectively analyzed the global burden of ischemic heart disease (IHD) and ischemic stroke (IS), 2 major contributors to the overall burden of MACE, by extracting data from the Global Burden of Disease database, and two-sample Mendelian randomization (MR) using the FinnGen R9 I9_CHD dataset as the outcome to investigate the genetically predicted associations between gut microbiota, immune cell traits, and major coronary heart disease events. In 2021, global IHD prevalence reached 254.3 million cases, a 1.4% increase from 1990, whereas IS prevalence declined by 39.6% over the same period. Results of Mendelian randomization analysis provided evidence supporting genetically predicted associations between 21 gut microbiota, 31 immune cells, and major coronary heart disease event. Sensitivity tests confirmed our findings. Additionally, mediation analysis suggested that the association between gut microbiota and major coronary heart disease event may be partly mediated through immune cell traits. Our study provides both an updated epidemiological profile of IHD/IS and genetic evidence linking gut microbiota and immune cell traits to coronary events, with immune cells potentially acting as mediators. These findings provide a foundation for future mechanistic studies and may facilitate the identification of candidate therapeutic targets, although further experimental validation is required.