34 Chapter 2 DISCUSSION The present study describes the sex-specific prevalence and clinical outcome of the different endotypes of symptomatic CCS patients referred for clinically indicated invasive coronary angiography in a large global patient cohort. The endotypes of CCS were comprehensively characterized by combined assessment of intracoronary pressure and flow to distinguish obstructive CAD, CMD and physiological normal endotype groups (Figure 4). The main study findings were as follows: In patients referred for invasive coronary angiography for the evaluation of CCS: 1) oCAD was significantly less prevalent and CMD was significantly more prevalent in women compared to men; 2) long-term cardiovascular outcomes (defined as TVF) were sequentially worst for patients with obstructive CAD, followed by patients with CMD. Conversely, patients with physiologically normal coronary arteries had the best long-term cardiovascular outcomes; 3) men experienced a worse 5-year TVF rate compared to women; 4) no sex-specific differences in prognosis was observed in the obstructive CAD, revascularization and CMD groups; and, 5) in the presence of oCAD (FFR≤0.80), men who underwent revascularization had lower risk of TVF at 5 years than men in whom revascularization was not performed. Conversely, this impact of revascularization was not identified in women. Invasive coronary physiological assessment in men and women Earlier studies have shown that women experience angina differently, have less extensive atherosclerosis and suffer from obstructive CAD less frequently compared to men.17-18 Yet, the prevalence of the distinct CCS endotypes across sexes encountered in catheterization laboratory in daily clinical practice is poorly understood. In the present large study, obstructive CAD was indeed less prevalent in women compared to men presenting with stable angina (15.5%, 210/1359 vs. 10.3%, 49/477). Additionally, we found a trend towards less revascularization in women compared to men (28.2%, 134/477 vs. 31.9%, 433/1359) suggesting an excess of obstructive CAD in men referred to the catheterization laboratory for suspected stable ischemic heart disease. This observation of the presence of exertional angina in the absence of obstructive CAD has been suggested by the Women’s Ischemia Syndrome Evaluation (WISE) study as being potentially related to a higher prevalence of CMD in women compared to men.5,19 However, the WISE-study is limited in its scope owing to its inclusion of only women. Accordingly, our study addresses this limitation by the inclusion of a multiethnic cohort of both men and women across multiple centers. Within this wider, clinically-representative, patient population, CMD was indeed significantly more prevalent in women compared to men (28.5% vs. 22.6%). Our findings are also consistent with a recent meta-analysis by Meliva et al.20, which similarly demonstrated a high pooled prevalence of CMD in ANOCA patients 41% (95% CI: 36–47%), with CMD being more prevalent in women compared to men
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