35 Sex Differences in Chronic Coronary Syndrome: Data from the ILIAS Physiology Registry (risk ratio 1.45). Our study complements the study of Meliva, which suffers from inherent limitations as a systematic review such as the a large heterogeneity in the incorporated studies, regarding prevalence of CMD, different inclusion criteria and methods to calculate CFR according to the studies. There is continued debate on the optimal invasive CFR cut-off value to define an abnormal result. Specifically, a recent ESC consensus paper16 recommends CFR≤2.0, whereas CFR ≤2.5 may better relate to pathophysiological changes in the coronary circulation and prognosis in ANOCA patient.16, 21, 22 Cognizant of these variations in CFR cut-off value, we performed our analysis according to both CFR≤2.0 and CFR≤2.5. Our results remained unchanged independent of the CFR cut-off value used. Therefore, regardless of the CFR-derived definition for CMD, CMD was more prevalent in women presenting with CCS compared to men. This consistent finding underscores the importance of detailed physiological interrogation of the coronary microcirculation for diagnostic purposes in both sexes once obstructive CAD has been ruled out. Prognostic values according to sex and CCS-endotypes In our study sex was an independent predictor of TVF at 5-year follow-up, with men demonstrating a worse prognosis compared to women. Presumably, this finding is driven by both an overrepresentation of men in the obstructive CAD and revascularization groups, as well as men having a worse prognosis in the normal coronary artery group compared to women. According to our results, men seem to benefit more from a revascularization compared to women. With respect to the finding that obstructive CAD and revascularization were more prevalent in men, this might be related to sex differences in atherosclerotic plaque size, composition and the propensity to rupture. Another hypothesis could be that women suffer from CMD after revascularization, in which the relationship between underlying CMD and coronary arteriosclerosis mediate a worse outcome.23 A recently published meta-analysis of Kelshiker et al. has shown that a reduced CFR is strongly associated with an increased risk of all-cause mortality and MACE across a broad range of patient groups and different pathologies.29 CCS-endotypes Of the total population, 30.8% of the patients had no evidence of abnormal coronary physiology as identified by combined pressure and flow measurements. There are several explanations for the angina-like symptoms in the absence of epicardial or microcirculatory disease. Vasomotor dysfunction presenting as coronary vasospasm can be caused by hyper reactivity of the vascular smooth muscle cells and encompasses focal or diffuse epicardial and microvascular vasospasm. Another cause of vasospasm is the acute activation of coronary mast cells. Mast cells play a role in regulating vascular function by producing vasoactive substance, such as histamine. The effect of histamine is mediated through activation of H1 and H2 coronary receptors. Coronary arteries can be hypersensitive to histamine, leading to vasoconstriction.24, 25 Vasospasm can be assessed 2
RkJQdWJsaXNoZXIy MTk4NDMw