Gut microbes are important for the development of atherosclerotic cardiovascular disease (ASCVD), and the dietary index for gut microbiota (DI-GM), a new measure of gut flora-friendly diets, has not been systematically investigated in relation to ASCVD. This study aimed to evaluate the correlation between DI-GM and the risk of ASCVD in American older adults, also to analyze the mediating role of body mass index (BMI). Researchers selected 2234 elderly participants ≥ 65 years of age from the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018 for a cross-sectional cohort study. Stratified analyses were taken based on DI-GM quartile. To achieve our research objectives, we employed logistic regression analysis, smooth curve fitting, interaction effects analysis, and mediation analysis. After adjusting for confounders, individuals with higher DI-GM had a significantly lower risk of ASCVD (highest quartile vs. lowest quartile OR = 0.73, 95% CI: 0.52–1.01, P < 0.001). DI-GM was linearly negatively associated with ASCVD (P = 0.13) and the association was stable in the diabetes subgroup (interaction P > 0.05), but age, gender and BMI may modify the association between DI-GM and ASCVD (interaction P < 0.05). BMI mediated 11.51% of the association between DI-GM and ASCVD (95% CI: 2.54%-54.1%, P = 0.016). DI-GM is likely to be a promising indicator for the assessment of the risk of ASCVD, with BMI exhibiting a partial mediating effect in this association. Future studies should prioritize a comprehensive investigation of the underlying mechanisms by which DI-GM contributes to atherogenesis, with the aim of enhancing the efficacy of early prevention strategies for ASCVD.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with atherosclerosis being the primary pathological substrate underlying most CVD. Epigenetics, defined as a set of regulatory mechanisms that dynamically modulate gene expression patterns or protein functional states through chemical modifications without altering the primary sequence of the genome, has been increasingly recognized as a pivotal driver in the pathogenesis of various diseases. Histone post-translational modifications, such as acetylation, methylation and lactylation, are catalyzed by specific enzymes and are essential for the regulation of gene expression, which in turn influences cellular functions and the progression of diseases. Notably, dysregulation of specific histone modifications is closely associated with the onset and progression of cardiovascular disorders. Accumulating evidence has demonstrated that aberrant histone modifications disrupt vascular cell homeostasis and contribute to atherogenesis by shaping the transcriptional landscape of vascular cells. On the one hand, histone modifications directly influence cellular functions (e.g., endothelial barrier integrity, macrophage lipid phagocytosis, and vascular smooth muscle cell phenotypic switching) and thereby drive atherosclerotic progression. On the other hand, these epigenetic modifications are dynamically modulated by major atherogenic risk factors, including dyslipidemia, pro-inflammatory cytokine release, and hemodynamic stimulation. This review focuses on the multifaceted roles of histone post-translational modifications in mediating vascular dysfunction during atherosclerosis, with an emphasis on the molecular mechanisms linking specific modifications to pathological cellular behaviors. Additionally, we highlight emerging therapeutic strategies targeting histone modification pathways, with the goal of advancing the development of precision diagnostics and interventions for atherosclerosis.