Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps

The existence of sex differences in the epidemiology, presentation, diagnosis, and management of coronary artery disease (CAD) has been a subject of growing inquiry for the past several decades. The prevailing paradigm is that the prevalence of anatomically obstructive disease of the epicardial coronary arteries is less common in women than similarly aged men, while nonobstructive and microvascular ischemic disease is more prevalent in women. Although both “patterns” of coronary atherosclerosis are associated with angina and cardiovascular events, the dominant diagnostic and therapeutic tools used in cardiology have focused on the male-predominant pattern of anatomically obstructive epicardial CAD. This has raised justified concerns about the under-diagnosis and under-treatment of symptomatic women with nonobstructive CAD. However, as recent research has begun to highlight the importance of nonobstructive CAD and coronary physiology in men as well as women, adjustments to this paradigm and greater attention to nonobstructive CAD are necessary. The present manuscript seeks to review key insights as well as substantial knowledge gaps regarding sex differences and nonobstructive CAD.