Coronary Artery Disease in Women: Sex-Specific Pathophysiology, Risk Factors, Clinical Presentation and Management

Cardiovascular disease remains the leading cause of mortality among women worldwide, yet coronary syndromes in women continue to be under-recognized and insufficiently represented in clinical research. This review summarizes sex-specific pathophysiological mechanisms, risk factors, clinical presentation, and management considerations in women with coronary syndromes. Women are more likely than men to present with non-obstructive and non-atherosclerotic ischemic phenotypes, including ischemia or angina with non-obstructive coronary arteries, coronary microvascular dysfunction, myocardial infarction with non-obstructive coronary arteries, spontaneous coronary artery dissection, vasospastic angina, and Takotsubo syndrome. These entities often require diagnostic strategies beyond the detection of flow-limiting epicardial stenosis, including cardiac magnetic resonance imaging, intracoronary imaging, and coronary function testing. Traditional cardiovascular risk factors remain important, but several female-specific risk enhancers, including premature menopause, adverse pregnancy outcomes, polycystic ovary syndrome, autoimmune disease, and psychosocial stressors, further modify risk and remain incompletely integrated into routine clinical assessment. Women may also experience diagnostic delays due to symptom misclassification, lower baseline troponin concentrations, and clinical algorithms historically derived from male-predominant populations. Management should follow guideline-directed therapy when appropriate, while recognizing sex-related differences in pharmacology, bleeding risk, revascularization outcomes, and the need for phenotype-specific treatment in INOCA, MINOCA, SCAD, and Takotsubo syndrome. Finally, transgender and gender-diverse individuals remain largely absent from cardiovascular trials, highlighting the need for inclusive research frameworks that distinguish sex, gender identity, and hormone exposure. Improved recognition of sex- and gender-related differences is essential to advance equitable cardiovascular care.