Sex Differences in Severity of Stroke in the INSTRUCT Study: a Meta‐Analysis of Individual Participant Data

Abstract

Background Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale. Methods and Results We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population‐based stroke incidence studies (1996–2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke‐related clinical factors, comorbidities, and pre‐stroke function were obtained. Within each study, relative risk regression using log‐binominal modeling was used to estimate the female:male relative risk ( RR ) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study‐specific unadjusted and adjusted RR s, controlling for confounding variables, were pooled using random‐effects meta‐analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male RR for severe ischemic stroke was 1.35 (95% CI 1.24–1.46). The sex difference in severity was attenuated after adjustment for age, pre‐stroke dependency, and atrial fibrillation but remained statistically significant (pooled RR adjusted 1.20, 95% CI 1.10–1.30). There was no sex difference in severity for intracerebral hemorrhage ( RR crude 1.08, 95% CI 0.97–1.21; RR adjusted 1.08, 95% CI 0.96–1.20). Conclusions Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre‐stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre‐stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex differences in stroke severity may also be warranted.

Sex Differences in Disease Profiles, Management, and Outcomes Among People with Atrial Fibrillation After Ischemic Stroke: Aggregated and Individual Participant Data Meta-Analyses

“…16 The details of the design of INSTRUCT have been described elsewhere. 6,17,18 This analysis focused on participants with IS and AF in the INSTRUCT, and included nine studies whose investigators have agreed to participate ( Supplementary Table S1). [19][20][21][22][23][24][25][26][27] These studies were conducted in Australia, New Zealand, Brazil, Greece, Sweden, Portugal, Italy, and Estonia between 1993 and 2014.…”

Gender Differences in Outcomes after Non-traumatic Intracerebral Hemorrhage

“…They attributed this mostly to pre-stroke risk factors and recommended improving pre-stroke health in elderly women. They also recommended further study in the biological origins of these gender differences [17]. Similar recommendations can likely be made for ICH.…”

Machine learning to predict mortality after rehabilitation among patients with severe stroke

“…The covariates examined included age (per 5-year increase), marital status (married/not married), hypertension, diabetes, COPD, history of CAD, AF, anemia, renal dysfunction, time from stroke onset to rehabilitation admission, ischemic stroke, dysphagia, neglect, and motor and cognitive FIM scores at admission. These variables were selected based on prior studies showing an association with the outcomes of interest 6,30,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] . A multivariate logistic regression analysis with backward stepwise selection (p > 0.20 for exclusion) was performed to assess the association of covariates with 3-year mortality.…”