The study examined the relationship between psychosocial stress and coronary heart disease (CHD) through DNA methylation analysis in postmenopausal women. The research included 3,857 women from the Women's Health Initiative who completed a questionnaire about stressful life events and provided blood samples. During follow-up averaging 16.7 years, 841 DNA methylation sites related to stress were identified. Created methylation risk scores (MRS) predicted CHD occurrence with 1.33-1.37 times higher risk and explained 16.5-17.7% of the association between stress and CHD. Results were independently validated in two additional studies. Cell-type-specific analysis revealed that the greatest number of stress-related methylation sites predicting CHD were found in monocytes. The study supports methylation scores as novel biomarkers for stress-related CHD.