Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia

Abstract

for the ISCHEMIA Research Group IMPORTANCE While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.OBJECTIVE To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. DESIGN, SETTING, AND PARTICIPANTSThis secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. INTERVENTIONS CCTA and angina assessment. MAIN OUTCOMES AND MEASURES Sex differences in stress test, CCTA findings, and symptom severity. RESULTS Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (352 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1363 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.3%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). CONCLUSIONS AND RELEVANCEWomen in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists

“…In a sub-analysis of the ISCHEMIA trial, women have more frequent angina with less extensive CAD and less severe ischaemia than men. 47 This was also shown in the large CorMICA trial. 48 These findings confirm important sex differences in the complex relationships between angina, atherosclerosis, and ischaemia.…”

“… 43 It is recommended to assess the CAC score in symptomatic women and those at intermediate cardiovascular risk. 43 , 47 …”

Sex differences in the association between PTSD symptoms with cardiac autonomic function and subclinical atherosclerotic risk

“…Conversely, our findings support a role for vasomotor dysfunction in the pathophysiology of PTSD‐mediated increases in CVD risk in women. Women have less atherosclerotic obstructive coronary disease than men but higher incidence of coronary vasospasm and stress‐induced myocardial ischaemia (Bairey Merz et al., 2006; Reynolds et al., 2020). It has been speculated that oxytocin release may alter functional connectivity between the ventromedial prefrontal cortex and amygdala diminishing anxiety and fear learning (Pooley et al, 2018a, 2018b).…”

COVID-19, the wake-up call for implementing sex and gender in cardiovascular disease

“… 7 Women have more frequent angina with less extensive obstructive coronary artery disease (CAD) and less severe ischemia than men. 8 , 9 In addition, coronary vasomotor disorders contribute importantly to the burden of anginal symptoms. Only recently, the first position paper has been published with clear guidance for patients with angina based on non-obstructive CAD (INOCA) with/without coronary vasomotor disorders.…”