DNA methylation mediates MBSR induced cardioprotection in patients after PCI.

Mindfulness-Based Stress Reduction (MBSR) improves well-being in acute myocardial infarction (AMI) patients, but its molecular cardioprotective mechanisms are unclear. In this prospective pilot study, 51 post-PCI AMI patients (17 MBSR plus standard therapy, 34 controls) were assessed for inflammatory markers (CRP, IL-6, PCT), echocardiography, and functional capacity at baseline and 6 months. Genome-wide DNA methylation profiling in a subgroup (n = 5/group) assessed changes from baseline to 6 months within MBSR and compared groups at the 6-month follow-up. At follow-up, the MBSR group showed greater reductions in CRP, IL-6, and PCT (adjusted P = 0.001, < 0.001, 0.003), alongside improved left ventricular ejection fraction, global longitudinal strain, wall motion score index, and 6-minute walk distance; all remained significant after false discovery rate correction (all q < 0.05). MBSR induced widespread DNA methylation changes (7,665 intra-group and 7,791 inter-group differentially methylated sites), which were nominally enriched in pathways related to immune response, inflammation, oxidative stress, and neuroendocrine (HPA axis) regulation. Exploratory uncorrected analysis linked BRD4 hypermethylation with lower CRP (ρ=-0.601) and improved GLS (ρ = 0.802), and PTTG1IP hypomethylation with improved LVEF (ρ = 0.717). These findings suggest MBSR modulates the DNA methylome within a novel "epigenetic-inflammatory-cardiac functional axis", providing a mechanistic framework for its cardioprotective effects.