Sex differences in characteristics, microbiology, management, and outcomes in infective endocarditis
Authors: Stahl A , Oestergaard L , Havers-Borgersen E , Emanuel Strange J , Voldstedlund M , Kober L , Fosboel E 
Published: November 2023

Abstract

Background
Infective endocarditis affects male patients more frequently, yet female sex has been associated with higher mortality rate in prior smaller studies. Unselected nationwide studies on sex differences in infective endocarditis are sparse and may help identify sex-related and universal prophylactic strategies.

Purpose
To investigate sex related differences in patient characteristics, practice patterns and outcomes in patients with infective endocarditis.

Methods
Between 2010–2020, we identified and characterized all patients with infective endocarditis according to sex. We used data from the Danish national registries including microbiological data, and outcome. Frailty was assessed by the sum of cardiovascular and non-cardiovascular comorbidities in each patient using the Hospital Frailty Risk Score. Mortality was compared in unadjusted analyses using Kaplan-Meier estimates for 90-day mortality following hospital admission and 5-year mortality following hospital discharge. In adjusted analyses, Cox regression was used for comparison of 90-day and 5-year mortality.

Results
We identified 6,259 patients with infective endocarditis including 2,047 (32.7%) female patients and 4,212 (67.3%) male patients. Female patients were older (median age 75.0 years (IQR 64.3–82.2 vs. 71.7 years (IQR 61.7–78.9) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%, p&lt;0.001). Female patients had lower education level, lower income and were more likely to live alone. Female patients had less cardiovascular comorbidity than male patients such as ischemic heart disease (25.2% vs. 34.8%), congestive heart failure (20.3% vs. 24.0%), prior myocardial infarction (7.8% vs. 14.3%), prosthetic heart valve (16.5% vs. 20.3%), and CIED (12.2% vs. 18.7%) (p&lt;0.01). Staphylococcus aureus was the most common microorganism in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus species than male patients (10.5% vs. 18.1%). Female patients were less often surgically treated (14.0% vs. 21.2%). The cumulative 90-day incidences of mortality from hospital admission were 30.9% (95% CI 28.9%–32.9%) in females and 23.6% (95% CI 22.3%–24.9%) in males (Figure 1). The cumulative 5-year incidences of mortality from hospital discharge were 59.8% (95% CI 57.4%–62.0%) in female patients and 53.0% (95% CI 51.3%–54.6%) in male patients. In adjusted analysis, female sex was associated with increased 90-day mortality (adj. HR 1.22, 95% CI 1.10–1.36), but no difference was found in 5-year mortality (adj. HR 1.02, 95% CI 0.93–1.12).

Conclusion
In infective endocarditis, female sex is associated with an increased 90-day mortality despite adjusting for age and frailty. However, this association is not found in long-term mortality. Female patients differ from male patients with lower prevalence of Enterococcus infective endocarditis and lower rates of surgery. Further research is needed to understand why these differences persist.