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New insights into sex differences – aortic stenosis, ischaemic heart disease and plaque progression

Three interesting presentations from the abstract-based on-demand programme at ESC Congress 2020 provide more evidence that sex really does matter in cardiology.

Coronary Artery Disease, Acute Coronary Syndromes, Acute Cardiac Care
Diseases of the Aorta, Peripheral Vascular Disease, Stroke
Cardiovascular Disease in Special Populations

In a Rapid Fire Abstract presentation, Doctor Yohann Bohbot (University Hospital of Amiens, France) described an analysis of 2,429 male (51.5%) and female (49.5%) patients with severe aortic stenosis. Women who presented with aortic stenosis were found to be older, were more often symptomatic, had smaller aortic valve area and greater ejection fraction than men. Of note, the cumulative 5-­year incidence of aortic valve replacement (AVR) was 79 ± 2% for men and only 70 ± 2% for women (p<0.001). Indeed, being male was independently predictive of AVR (odds ratio 1.49; 95% confidence interval [CI] 1.18–1.97; p=0.011). Estimated 5-year survival was lower for women compared with men (62 ± 2% vs. 69 ± 1%, respectively, p<0.001). However, after propensity matching for patient characteristics and management (AVR), women had better 5-year survival than men (69 ± 2% vs. 62 ± 2%; p=0.023), as seen in the general population. The authors concluded that excess mortality in women appears to be related to a combination of late diagnosis plus less frequent and later AVR referral than in men.

Disparities by sex were also seen in an ePoster about patients with ischaemic heart disease (IHD) and left ventricular dysfunction, which was first-authored by Doctor Misha Dagan (The Alfred Hospital, Melbourne, Australia). Data were prospectively collected from a multicentre registry database (2005–2018) on pharmacotherapy after percutaneous coronary intervention (PCI) and long-term mortality (median 4.7 years follow-up) in IHD patients with left ventricular ejection fraction <50%. Of the total 13,015 patients analysed, 2,634 (20.2%) were women.

Overall, a similar proportion of women (72.7%) and men (72.2%) were on optimal medical therapy (OMT) at 30 days, defined as a beta­blocker and an angiotensin­-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) ± mineralocorticoid receptor antagonist (MRA). However, women were less likely to be on an ACEi/ARB than men (80.4% vs. 82.4%; p=0.02) and more likely to be on an MRA (12.1% vs. 10.0%; p=0.003). Aspirin use was similar between sexes (95.3% vs. 95.9%), while women were less likely to be on statins (93.5% vs. 95.3%, p<0.001) and a second antiplatelet agent (94.4% vs. 95.6%; p=0.007). Women had significantly higher unadjusted long­term mortality of 25.4% compared with 19.0% for men (p<0.001). Moreover, Kaplan­-Meier analysis demonstrated that men on OMT had the longest survival overall and women on sub-­OMT had significantly poorer outcomes compared with men on sub­-OMT over 14 years. After adjusting for OMT and other comorbidities, there was no difference in long­-term mortality between sexes (hazard ratio 0.99, 95% CI 0.87–1.14; p=0.94), suggesting that increased unadjusted long­-term mortality in women is likely due to differing baseline risk.

Related to physiological differences, Doctor Mohammed El Mahdiui (Leiden University Medical Center, the Netherlands) and co-investigators presented an ePoster on the natural history of plaque progression in females and males. Studies have previously been performed in high-risk populations needing invasive imaging; however, the current investigation used serial coronary computed tomography angiography, which permits fast and non-invasive quantification of coronary artery disease in low-intermediate risk patients.

In this per-lesion analysis of 211 patients (male, 69%; female, 31%), males had larger fibro-­fatty percentage atheroma volume (PAV) compared with females, although the rate of change did not differ. Younger women <55 years showed more regression of fibrous PAV and non-­calcified PAV compared with males. No differences in the rate of plaque progression or plaque composition changes were seen between males and females in the older age group.

Analyses such as these highlight the physiological differences between sexes and also potentially avoidable discrepancies with respect to treatment – both aspects require further research and appropriate measures to ensure that all patients, whatever their sex, receive optimal care.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.