24 Chapter 2 INTRODUCTION Chronic coronary syndrome (CCS) remains the leading cause of death worldwide in both men and women.1-3 CCS has multiple underlying pathophysiological mechanisms and clinical presentations. Classically, CCS has most frequently been associated with the presence of obstructive epicardial coronary artery disease (oCAD). However, more recently, there is an increasing understanding of the role of coronary microvascular dysfunction (CMD) in the pathophysiology, symptomatology and adverse clinical outcome of patients with CCS. To date, the invasive diagnosis of CCS has focused mainly on the detection of oCAD, which is known to be more prevalent in men than women 4, 5 irrespective of the presence of typical angina symptoms or positive non-invasive ischemia testing.5, 6 Despite this, there exists an apparent clinical outcome paradox, with women more frequently experiencing cardiovascular death in CCS compared to men.7 One hypothesis to explain this differential outcome between the sexes in CCS may be that there is a higher prevalence of CMD, and thus adverse cardiovascular outcome,8 in women as compared to men.7-9 However, data supporting this rationale is currently lacking, owing to previous studies reporting on sex differences in the prevalence of CMD being small and in highly selected patient groups. Accordingly, in order to adequately inform on the prevalence of CMD in symptomatic patients with CCS presenting to the catheterization laboratory, we investigated the relationship between patient sex and the different endotypes of CCS, as well as their association with long-term clinical outcomes in the large multicenter ILIAS registry. PATIENTS AND METHODS Study population The ILIAS registry is a multi-center, global registry of patients with accompanying comprehensive invasive epicardial and microvascular physiological assessment and associated clinical outcomes. The registry consists of prospectively gathered from 20 expert medical institutes in the Netherlands, Korea, Japan, Denmark, Spain, Italy and the United States of America. Patients were enrolled into the ILIAS registry if they underwent clinically indicated coronary angiography and comprehensive invasive physiological assessment of at least one native coronary artery. Patients with hemodynamic instability, significant valvular pathology, prior coronary artery bypass graft surgery, as well as culpritvessels of acute coronary syndromes were excluded.
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