Beyond Coronary Stenosis: A Mechanism-Based Approach to Ischemic Heart Disease in Women

Despite major advances in cardiovascular medicine, ischemic heart disease (IHD) in women remains underrecognized and undertreated. A substantial proportion of symptomatic women have no flow-limiting epicardial stenosis, and ischemia may arise from coronary microvascular dysfunction, vasospasm, diffuse atherosclerosis, plaque-related mechanisms, spontaneous coronary artery dissection (SCAD), or combinations of these processes. Female-specific biological factors—including hormonal transitions, vascular aging, inflammation, metabolic changes, and reproductive cardiovascular risk enhancers—modify the coronary substrate across the life course. This review integrates these determinants with contemporary coronary phenotyping and proposes a clinically oriented, mechanism-based framework for IHD in women. Multimodality imaging, invasive coronary functional testing, and intracoronary imaging are considered complementary tools for identifying predominant and coexisting mechanisms. Management should combine guideline-directed cardiovascular prevention with mechanism-targeted antianginal therapy and women-specific considerations, including reproductive planning, pregnancy counseling, medication safety, and psychosocial care. This framework is intended as a practical synthesis rather than a validated classification system and aims to support more precise diagnosis and individualized treatment of women with ischemic symptoms.