Women Show Lower Risk of Early Stroke Deaths, Poststroke Infections

Investigators suggest that sex-specific strategies should be invoked to reduce the amount of early stroke deaths after observations suggest that female sex is linked to lower risk of stroke-related events.

A study published in Neurology Clinical Practice found lower risk of 30-day death after stroke was associated with female sex, when compared with male sex. According to investigators, this may be explained by a survival advantage in poststroke infections for women.

A total of 17,956 patients with acute ischemic stroke were included, 41.3% of whom were women (n = 7413). During the 30 period after stroke onset, the cumulative number of all-cause deaths was 219 for men (2.1%) and 230 for women (3.1%). Although this crude 30-day death rate was higher in women than in men (HR, 1.50; 95% CI, 1.25-1.80), adjustment for age and stroke severity revealed a lower risk for women (HR, 0.76; 95% CI, 0.62-0.92). Inclusion of prestroke mRS score, however, did not reduce the HR for 30-day death in women compared to men (HR, 0.93; 95% CI, 0.76-1.113). 

In the first 5 days after stroke onset, a total of 167 deaths (37.2%) occurred, with 137 due to direct neurologic sequelae (82.0%), 10 due to acute infections (6.05%), and 20 due to other causes (12.0%). When looking at overall deaths within 30 days, proportions were 47.0% due to neurologic sequelae, 24.3% due to acute infections and 28.7% due to other causes. Using competing risk models, analyses suggested women were less likely to die due to acute infections, with a subdistribution HR of 0.33 (95% CI, 0.20-0.54). 

Investigators, including corresponding author Masashiro Kamouchi, MD, PhD, Department of Health Care Administration and Management, Graduate School of Medical Sciences, in Kyushu, Japan, further evaluated the association between sex and occurrence of acute infection during stroke treatment in 13,821 patients with a hospital stay of 30 days or less, including 5496 women (39.8%). Women were found to be associated with lower risk of acute infections during hospitalization (odds ratio, 0.62; 0.52-0.74) and lower risk of death due to such infections (subdistribution HR, 0.52; 95% CI, 0.33-0.83). 

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“Despite the growing awareness of the importance of reducing deaths caused by secondary complications after stroke, little attention has been given to sex differences in the risk of death from poststroke complications,” Kamouchi et al wrote. “Our results suggest a higher risk of death from infections after ischemic stroke in men, emphasizing the need for sex-specific strategies for the early prevention and improved management of poststroke infections.”

Participants were included form the Fukuoka Stroke Registry (FSR), a multicenter hospital-based registry in which 18,165 patients were enrolled between June 2007 and September 2019 for acute ischemic stroke, including transient ischemic stroke. After excluding 209 patients with missing data, 15,554 patients were included in the the follow-up study, comprising the prospective cohort, and anonymized data was included from 2402 patients, comprising the retrospective cohort, which were then included in the survival analysis. In both the prospective cohort (n = 12,018) and retrospective cohort (n = 1803), analyses of acute infections were limited to 13,821 patients who were hospitalized for 30 days or less. 

When analyzing differences in baseline characteristics between men and women, women were generally older and more likely to have dyslipidemia, atrial fibrillation, and chronic kidney disease. Although, women were less likely to have diabetes mellitus and prior stroke, and generally had lower body mass index. A higher number of women were categorized as dependent before the index stroke, with higher prestroke mRS scores. More severe neurologic impairment at admission, higher incidence of cardioembolic stroke, and receipt of reperfusion therapy were all also more likely for women than men. 

Limitations were cited due to the inclusion of patients from FSR participating hospitals, impacting generalizability of results, and the lower number of deaths within 30 days compared to other studies. Investigators attribute this to the registry including transient ischemic stroke patients, and the expertise of FSR participating hospitals. Selection bias could have been introduced due to the exclusion of patients with missing data and hospital stays longer than 30 days. Also, a lack of data on status following discharge to 30 days after stroke onset, impacting investigators’ ability to account for any deaths hat might have occurred in the retrospective cohort. The study focused on sex and not gender, which may limit the applicability of data to patients with discordant sex assigned at birth and gender. 

REFERENCE
Irie F, Matsuo R, Nakamura K, et al. Sex differences in the risk of 30-day death after acute ischemic stroke. Neurol Clin Pract. 2021;11(6):e809-e816. doi:10.1212/CPJ.0000000000001087