Comprehensive Endotyping of Patients With Angina and Nonobstructive Coronary Arteries: A Report From the J‐CMD

BACKGROUND: Angina with nonobstructive coronary arteries (ANOCA) is frequently driven by coronary vasospasm and coronary microvascular dysfunction (CMD). Despite recommendations for comprehensive invasive testing to phenotype ANOCA, prospective data on the prevalence and interplay of these endotypes remain limited. We aimed to investigate the prevalence, clinical correlations, and overlap of epicardial vasospasm, microvascular spasm, and CMD, defined by a coronary flow reserve <2.0. METHODS: We analyzed the data from a prospective, multicenter nationwide registry of the J-CMD (Japanese Association of Coronary Microvascular Dysfunction; UMIN000047609). Patients with ANOCA underwent standardized intracoronary functional testing, including acetylcholine-based spasm provocation and coronary flow reserve assessment. The distribution of the endotypes (epicardial vasospasm, microvascular spasm, isolated CMD, and CMD with spasm) was investigated according to sex and age tertiles. RESULTS: =0.011). While microvascular spasm was more prevalent in women, CMD was associated with older age, female sex, hypertension, and diabetes. Intriguingly, the prevalence of these endotypes varied with age in women, a pattern not observed in men. CONCLUSIONS: Among patients with ANOCA, coronary vasospasm and CMD were prevalent and frequently coexisted, demonstrating distinct sex- and age-related patterns. These findings offer novel insights into the heterogeneous pathophysiology of ANOCA and reinforce the importance of comprehensive invasive assessment in establishing a precise diagnosis and guiding targeted therapy.