Impact of Sex Difference on Severity and Functional Outcome in Patients with Cardioembolic Stroke

https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.07.016Get rights and content

Introduction

Female sex is a risk factor for thromboembolic events in Caucasian, but not in Japanese, patients with nonvalvular atrial fibrillation. However, it remains unclear whether the female sex is also a risk factor for severe stroke and unfavorable functional outcome in patients with cardioembolic (CE) stroke.

Methods

Three hundred fifty-five consecutive patients with CE stroke within 48 hours after onset and with a modified Rankin Scale (mRS) score of 1 or lower before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between female (n = 157) and male (n = 198) patients.

Results

The mean age was higher in female than in male patients (80 ± 8 versus 75 ± 9 years, P < .00001). The congestive heart failure, hypertension, age [≥ 75 years], diabetes, stroke/transient ischemic attack [TIA] (CHADS2) score before onset was similar between the two groups (median, 3 [2-4] in both groups). Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale (NIHSS), was higher in female than in male patients (13 [5-20] versus 8 [3-16], P = .0009). Functional outcome at discharge, assessed by mRS, was unfavorable in female than in male patients (3 [1-5] versus 2 [1-4], P = .005). An mRS score of 3 or higher at discharge was found more in female than in male patients (59% versus 39%, P = .0001). Multivariate analyses confirmed that female sex was a significant determinant of severe stroke (NIHSS ≥ 8) on admission (odds ratio [OR] to male = 1.97; 95% confidence interval [CI]; 1.24-3.15, P = .004) and for the mRS score of 3 or higher at discharge (OR = 1.83; 95% CI, 1.16-2.89; P = .01). Similar results were obtained by propensity-score matching analysis.

Conclusions

Female sex is a risk factor for severe stroke on admission and unfavorable functional outcome at discharge in Japanese patients with CE stroke.

Introduction

Female sex is a risk factor for thromboembolic events in patients of the Caucasian population with nonvalvular atrial fibrillation (NVAF).1 Accordingly, recent European and American guidelines recommend the congestive heart failure, hypertension, age [>75 years], diabetes, stroke/TIA, vascular disease, age [65-74 years], sex category [female] (CHA2DS2-VASc) score for thromboembolic risk stratification in patients with NVAF, which includes female sex (Sc) as a risk factor.2, 3 In contrast, female sex is not a risk factor for thromboembolic events in Japanese patients with NVAF.4 More importantly, when cardioembolic (CE) stroke occurs in patients with NVAF, it is still uncertain whether female sex is also a significant risk factor for severe stroke and unfavorable functional outcome. In the present study, we assessed this critical issue in Japanese patients with CE stroke.

Section snippets

Study Patients

Hirosaki Stroke and Rehabilitation Center (HSRC) has both a stroke care unit for acute therapy and a stroke rehabilitation unit for further rehabilitation therapy. Accordingly, all patients with acute ischemic stroke admitted to HSRC receive consistent therapies in the acute phase and subsequently in the chronic phase during hospitalization.

During a 3-year period from April 2011 to March 2014, a total of 516 consecutive patients with CE stroke were admitted to the HSRC for acute therapy within

Patient Profiles

A comparison of the clinical characteristics of the female and male patients in this study is shown in Table 1. The mean age was significantly higher in female than in male patients. All female patients were menopausal. The CHADS2 score was similar between the two groups, whereas the CHA2DS2-VASc score was significantly higher in the female than in the male patients, because this score includes female sex (1 point) as a risk factor by definition. Congestive heart failure was found more in the

Major Findings

In the present study, we found that female sex in patients with CE stroke is a significant predictor of severe stroke on admission and unfavorable functional outcome at discharge. Although female sex is not a risk factor for thromboembolic events in Japanese patients with NVAF,4 the present findings may lead to sex-specific prevention and treatment of CE stroke, especially focused on female patients.

Severe Stroke and Unfavorable Functional Outcome in Female Patients with CE Stroke

A number of studies investigating sex difference in stroke severity and functional outcomes in

Conclusions

Female sex is not a risk factor for thromboembolic events in Japanese patients with NVAF,4 but a risk factor for stroke severity and unfavorable outcome in patients with CE stroke. It is of significant interest to determine whether there is a racial difference in this discrepancy. In view of the clinical setting, more sex-specific prevention and treatment of CE stroke, especially focused on female patients, are warranted.

Acknowledgment

We gratefully thank Ms. Hiroko Kogawa for excellent technical support.

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Sources of funding: Dr. Hirofumi Tomita received research funding from Bayer HealthCare; Dr. Joji Hagii received research funding from Bayer Healthcare, and Speakers' Bureau/Honorarium from Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, and Pfizer; Dr. Norifumi Metoki received Speakers' Bureau/Honorarium from Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, and Pfizer; Dr. Minoru Yasujima received Speakers' Bureau/Honorarium from Bristol-Myers Squibb and Pfizer; Dr. Ken Okumura received research funding from Boehringer Ingelheim, Bayer Healthcare, and Daiichi-Sankyo, and Speakers' Bureau/Honorarium from Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Eisai. The other authors have no disclosure.

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