The ISCHEMIA trial will keep shedding light. The latest data show important differences between men and women as regards disease severity and its correlation with symptoms. Women have more angina than men but have less extensive ischemia.
These findings were presented virtually at the ACC 2020, cancelled by COVID19, and suggest that, in addition to obstructive coronary artery disease, other factors might play a role.
Why do women show more symptoms? A reductive point of view claims they have a different pain threshold, but there might be other factors at play. There are several interesting hypotheses (especially suitable for quarantine) from differences in myocardial innervation to differences in endothelial function, and microvascular function. A few studies even suggest emotional stress most likely is what triggers ischemia in women and this would not be associated to obstructive CAD severity.
Whatever the answer, something is obvious: women behave differently compared to men when it comes to ischemia and symptoms. At first glance, there is nothing striking about this old information. However, this outdated information had multiple confounders that the ISCHEMIA study does not have.
The ISCHEMIA randomized 5179 patients to an invasive strategy of coronary angiography followed by revascularization, when needed, plus optimal medical treatment vs. an initial conservative strategy vs. optimal medical treatment alone.
Patients were randomized prior angiography and blinded coronary CT angiography that ruled out left main disease (or any disease of comparable severity), while confirming the presence of CAD.
Out of 2262 women and 6256 men evaluated (not all were randomized, hence the difference in n), women more often presented non obstructive CAD vs. men (34% vs 11%; p<0.001). Obstructive CAD was defined as lesions of at least 50% stenosis in any epicardial vessel. Seeing as one of the inclusion criteria of this study was the presence of obstructive CAD, it included far fewer women.
In the randomized cohort, women presented less ischemia in the stress imaging, a difference driven by patients undergoing nuclear stress imaging. The echo stress test did not show significant differences in ischemia severity between both sexes.
Despite the less amount of obstructive CAD and the less severe results by nuclear stress imaging, women referred significantly more symptoms. Compared against 37% of men, only 27% of women claimed to be symptom free (p<0.001). On multivariable analysis, female sex resulted an independent predictor of angina (OR 1.41; 95% CI 1.13-1.76).
Original Title: Sex differences in severity of coronary artery disease, ischemia, and symptom burden in patients with moderate or severe ischemia: insights from the ISCHEMIA trial.
Reference: Reynolds HR et al. ACC 2020 virtual.
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