Background: Over half of women who present with angina are found to have negative coronary angiographic assessments. Of these patients, up to 50% are diagnosed with coronary microvascular dysfunction (CMD), which refers to pathologic changes within the small vessels of the coronary circulation. The hallmark of the pathophysiology of CMD is that endothelial damage, which occurs due to a multitude of conditions and risk factors, is the inciting event for the development and progression of CMD. CMD leads to a mismatch in myocardial demand and perfusion, leading to signs and symptoms of cardiac ischemia in the absence of obstructive lesions in the major vessels. CMD can be diagnosed through a variety of both invasive methods that allow a more specific evaluation of the microvasculature and non-invasive imaging techniques, such as cardiac positron emission tomography (PET) and magnetic resonance imaging (MRI). Risk factors for CMD overlap significantly with those of obstructive coronary artery disease (CAD)-hypertension, hypercholesterolemia, and diabetes remain salient predictors. However, these conditions only account for 20% of CMD cases in females.

Findings: Women have sex-specific risk factors such as menopause, pregnancy, polycystic ovarian syndrome (PCOS), and a higher proclivity toward chronic inflammatory disorders. Estrogen has a cardioprotective effect by increasing production of nitric oxide, a potent vasodilator released by endothelial cells. As a result, the hormonal changes of menopause may accelerate endothelial damage, and in turn, CMD. Current treatments focus on addressing the risk factors of cardiovascular disease, such as anti-hypertensive drugs, weight loss, and glucose control.

Conclusion: Given the multifactorial nature of CMD in women, and the extensive atypical risk factors for cardiac disease, a more nuanced approach is needed that addresses the varied pathophysiology of CMD.