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

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Abstract

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 article seeks to review key insights as well as substantial knowledge gaps regarding sex differences and nonobstructive CAD.

Section snippets

Background

Ischemic heart disease (IHD) is the leading cause of mortality of women in all age groups [1]. At 50 years of age, the average lifetime risk of developing IHD in women is approximately 40% [2]. Overall, despite mortality from IHD in the United States steadily declining from the 1960s, the rate of mortality reduction in women has down-trended more slowly than that of men [1]. The exact factors contributing to poorer outcomes for women diagnosed with IHD have yet to be fully elucidated, but there

Challenges in detection

Among those with stable IHD, defined as chronic stable angina due to epicardial stenosis, microvascular dysfunction, vasospasm or symptomatic ischemic cardiomyopathy, nearly 60–70% of women and 30% of men have nonobstructive CAD [6]. However, it is challenging to determine the exact prevalence of nonobstructive CAD because of the aforementioned definitional heterogeneity as well as because the diagnosis has long been contingent on the performance of ICA. Studies have estimated a prevalence of

Assessment: Recent insights and shortcomings

As a consequence of the heterogeneity of definitions and the much greater attention to obstructive CAD, the assessment and risk stratification of nonobstructive CAD is far less elaborated. Nonobstructive CAD encompasses a wide spectrum of findings spanning minimal plaque to diffuse atherosclerosis. The risk of events appears to increase stepwise with the global atherosclerotic burden as defined by coronary segments with plaque by CCTA [28] or vessels diseased by ICA [7], although the

Treatment: More knowledge gaps than evidence

The substantial knowledge gaps regarding the ideal treatment of nonobstructive CAD have only recently gained wider attention. Overall, there are no specific guideline recommendations for this group of patients beyond risk factor modification. The preponderance of large secondary prevention trials required either anatomically obstructive CAD or a clinical event (e.g., myocardial infarction) for entry and excluded patients with nonobstructive disease. In contrast, trials specifically focusing on

Conclusions

After being overlooked for long, there is increasing appreciation of the clinical significance of nonobstructive CAD. Advances in both noninvasive and invasive testing will undoubtedly continue to challenge the paradigm that this is a “women׳s problem” while providing insights into meaningful sex differences. Although at present there are substantial knowledge gaps, it is hoped that ongoing research efforts will continue to improve the detection, assessment, and treatment of nonobstructive CAD

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    The authors have indicated that there are no conflicts of interest.

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