Outcomes following acute stroke may vary depending on the gender of the patient (1, 2). Stroke is more common in women, among whom it is the fourth leading cause of death, as compared to the fifth leading cause in men (3, 4). The death rate following stroke is higher in women (women: 6.2%; men: 4.4%), resulting in 55,000 more excess deaths among women annually (3, 4). Stroke rates are especially high in women in the older age category (>80 years of age) (5). In women, stroke is the most common presentation of cardiovascular disease, whereas the leading manifestation in men is coronary artery disease (6). There is evidence that modifiable risk factors for stroke may affect men and women differently. For example, the effect of diabetes on stroke risk is greater in women compared to men (7). This is especially evident in the case of type 1 diabetes (7–9). Similarly, recent evidence suggests that hypertension may have a stronger association with stroke in women compared to men (8, 10, 11). There is also an association between increased body mass index (BMI), or obesity, and stroke, and this association also appears to be more prominent in women (8). Atrial fibrillation, an important risk factor for stroke, is more frequent in women (7), and the risk of stroke is particularly high in women older than 65 years of age (12). Additionally, there are several important female-specific risk factors that also contribute to the risk of stroke in women (13–15).

Women are less likely to receive appropriate treatment for acute stroke (1, 2). Several factors may contribute to the provision of suboptimal treatment for women. First, the diagnosis of acute stroke is often missed in women. In a recent cross-sectional analysis of misdiagnosis of acute stroke, women had 25% lower odds of the correct diagnosis being made (16, 17). A higher frequency of atypical stroke symptoms in women may contribute to the misdiagnosis of stroke (18). We have previously shown that stroke mimics are more common in women (19). This may also contribute to higher rates of misdiagnosis and delays in treatment. A recent meta-analysis showed that thrombolysis was offered less frequently to women, and that results indicating lower rates of treatment with rt-PA occurred most frequently in reports from Europe and the USA (20). Women are also more likely to have severe symptoms, another factor that contributes to poor outcomes following acute stroke (21).

Most of the sex- and gender-related research on stroke diagnosis, treatment, and outcomes has been published in Europe and North America (1, 2). The effects of gender and sex on outcomes of stroke have not been thoroughly studied in populations in the Middle East or Southeast Asia. Regarding Qatar specifically, we have previously published work on the topics of ethnic variation (22), stroke risk factors (23), clinical presentation (24), thrombolysis in acute stroke management (25), and short-term (26) and long-term (27) outcomes of stroke in the population of Qatar. We have also shown that post-stroke depression tends to be more common in women in Qatar (28). We now present our experience based on analysis of a large database of prospectively collected data on 7,300 patients; using these data, we studied the risk factors, presenting symptoms, administration of reperfusion treatment, course of disease during hospital stay, and short- and long-term prognosis in male and female patients admitted to the hospital following acute stroke.

All patients with acute ischemic stroke (AIS) who were admitted to the Hamad General Hospital (HGH) between January 2014 and January 2022 were included in the study. Clinical information was entered prospectively in a database, as reported in previously published work (22–24). The hospital has a dedicated stroke ward, admits more than 95% of stroke patients in Qatar, and is the only center where AIS treatment with intravenous thrombolysis and mechanical thrombectomy is offered. The clinical information collected on all patients admitted to the HGH included prehospital Modified Rankin Scale (mRS) score, vascular risk factors, mode of transportation, symptom severity, time to CT, and “door-to-needle” time in cases where thrombolysis was offered. Clinical evaluation included the severity of stroke as measured by the National Institute of Health Stroke Score (NIHSS). Treatment at admission and discharge was recorded for all patients. We also documented any medical complications that developed during admission, including aspiration pneumonia, bedsores, bladder infections, and any systemic sepsis. All patients were assessed on the mRS at discharge and at 90 days following acute stroke. In the current study, we also reviewed the state-wide Cerner medical records of the patients to document any vascular complications following discharge.

We evaluated differences between men and women in terms of mode of transportation to the hospital, time from onset to presentation to the emergency department, severity of stroke symptoms, type of stroke, and whether the patient was treated with thrombolysis and thrombectomy. In addition, we monitored the rate of complications, length of stay in the hospital, and changes in treatment of risk factors at the time of discharge. The primary short-term outcome measure in the present study was a comparison of mRS scores at 90 days between female and male patients. An mRS score of 0–2 was considered a good outcome, and an mRS score of 3–6 was defined as a poor outcome. For analysis of long-term outcome, we compared the rate of major adverse cardiovascular events (MACEs) among men and women at 1 year. The occurrence of MACEs (defined as cardiovascular mortality; all-cause mortality; fatal or non-fatal myocardial infarction; recurrent stroke; and revascularization procedures, i.e., coronary artery bypass graft or percutaneous coronary intervention) during follow-up after the index event was also compared.

The study was approved by the Institutional Review Board, Hamad Medical Corporation at the Medical Research Center (MRC-01-20-1135) and the Institutional Review Board of Weill Cornell Medicine—Qatar (1932095-1/22-00016).

Informed consent: This was a registry study; hence, consent was not applicable.

This is the largest study using prospectively collected data on the role of sex in terms of evaluation, management and prognosis, and long-term outcomes for ischemic stroke patients in the Middle East. The patients represented multiple ethnicities, but were predominantly Arabic or from Southeast Asia. The significantly higher average age among women reflected the disproportionately high number of young male expatriate workers in Qatar compared to women, as we have previously reported (22–26). We have previously shown that stroke occurs at a younger age among expatriate subjects and that this is likely to be related to undiagnosed or poorly controlled risk factors. We have also previously shown that a higher incidence of lacunar stroke occurs among patients with a low NIHSS score, which is also related to poorly controlled hypertension and diabetes (22–26).

The present research revealed that, despite presenting with more severe stroke, women reported to the hospital later, underutilized the ambulance service, and were significantly less likely to receive intravenous thrombolysis treatment. In addition, the time to treatment (door-to-needle time) was also significantly delayed in women compared to men. The significantly higher rate of medical complications among women while in hospital can be explained by the older age of this group, the higher incidence of diabetes and obesity, and the likelihood of more severe stroke at presentation. These are all likely contributors to lower rates of recovery at discharge and at 90-day follow-up. Despite greater severity of stroke, fewer women than men were admitted for rehabilitation. Our research also showed that the incidence of MACEs during the 1-year follow-up period was significantly higher among women. This may in part be explained by their older age and the more frequent presence of diabetes. However, significantly fewer women were receiving antithrombotic, antidiabetic, or statin medications at the time of discharge, even though the incidence of diabetes was higher in women. These are important observations and require further analysis in the context of previously published literature on women and stroke. Special attention is required for women in order to improve awareness of the early signs of stroke, achieve rapid admission to the hospital, increase provision of reperfusion treatment, improve provision of care to prevent acute stroke-associated medical complications, and provide aggressive post-stroke care to improve prognosis and decrease the incidence of MACEs during follow-up.

Stroke is more common in women compared to men throughout life (1), and is especially prominent as a cause of death in the elderly (29). Elderly women are more likely to live alone and to have a higher degree of disability, making it more difficult for them to reach the hospital in good time (29). Treatable risk factors, including hypertension, diabetes, and atrial fibrillation, are also more common in the elderly and (as was evident from our study) may be undertreated. In our study, 50% of female patients with atrial fibrillation were not taking anticoagulation medication, and this likely accounted for the higher rate of cardioembolic stroke. We also observed that the use of statins was significantly lower in female patients at the time of discharge, despite this group having a significantly higher incidence of diabetes. Undertreatment of diabetes (30) and lower rates of statin use (31) in women have previously been noted. The use of antithrombotic medications was also significantly lower in women, an observation that has previously been noted (21). Our study shows that there focused attention needs to be placed on better management of vascular risk factors before and after stroke. Given the high rates of MACEs observed in women, this is especially critical following discharge after admission for acute stroke.

Women are significantly delayed in their arrival at the hospital and are less likely to receive rt-PA (32). In our study, fewer female patients presented within the 4.5-h time window, and women were less likely to use the ambulance service, which contribution to delay in their evaluation. The longer door-to-needle time observed in our study may also be a contributing factor in the fact that fewer female patients make a good recovery (33). Furthermore, women experience significantly higher rates of medical complications during hospitalization. Medical complications, especially aspiration pneumonia and sepsis, are important causes of increased mortality in stroke patients (34) and have been underreported in recent reviews on stroke in women (1, 2). Older age at presentation and greater neurological deficits at presentation are also important risk factors for medical complications in acute stroke patients. The combination of these factors likely contributed to the longer hospital stays and higher rate of mortality observed in women in our study. In our study, these higher rates of poor recovery and mortality in women persisted even after correction for the age difference in our multivariate analysis.

Our study showed a significantly lower rate of good recovery in women compared to men. Multiple factors likely contributed to this difference, as discussed above in detail. Women had a 50% lower rate of recovery even after correction for age, risk factors, and occurrence of complications in the hospital. However, a meta-analysis published recently has suggested that baseline differences in age, vascular risk factors, and stroke etiology can explain most of the sex-related difference in mortality (2, 35). In our population, the higher door-to-needle time for women may also be related in part to local social and ethnic practices. Traditionally, treatment-related decisions are made by male members of the family. It is not uncommon to wait for a male family member (for example, the patient's husband or brother) to arrive at the hospital before treatment can be initiated.

Few studies have been conducted on the long-term risk of MACE in women (1–4). We have previously shown that depression is more common in women following a stroke in our population (28), and depression has been found to be associated with slower post-stroke recovery (28). There are additional significant factors that may also contribute to the fact that fewer women make a good recovery and that MACEs occur at higher rates in women. Women are more likely to experience mobility issues (36), cannot tolerate pain well (1, 2), and are more likely than men to be single or widowed (1, 2). In a recent study conducted in London, in which patients were followed for more than 10 years following acute stroke, women were older and had significantly poorer outcomes in terms of activities of daily living (37). Despite their older age at presentation, women were less likely to experience recurrent strokes and had a lower rate of death during follow-up (37). In our study, we observed a higher rate of MACE in women during 1-year post-stroke follow-up. This may in part be related to lower rates of preventive treatment at the time of discharge. Despite the higher incidence of diabetes in women, we noticed that the use of antidiabetic medications and statins was lower in women than in men.

Our study shows that attention to some of the factors identified may lead to better outcomes in female patients. Vascular risk factors, especially diabetes, hypertension, obesity, and atrial fibrillation, were more common in women, and yet at the time of discharge, women were less likely to be offered statins and antithrombotic medications. Women were also less likely to receive rehabilitation treatment and had higher all-cause mortality during follow-up. Attention to strategies that may improve early admission to hospital, higher rates of thrombolysis, reduction in medical complications, and improved management of vascular risk factors may contribute to improving the care of female patients who suffer from acute stroke. The results are similar to those of a recent report from China on 9,038 patients, among whom stroke occurred at an older age and the outcomes were worse in women (38). The unfavorable outcome remained after correction for age, risk factors, and onset-to-door time (38). Lower acceleration of biological age for ischemic stroke in women may in part explain the older age at presentation (39).

There are limitations to our study. This was a single-center study and therefore may not reflect stroke practices across the entire Middle East. The data were collected prospectively for entry into the Qatar stroke database, but the analysis was retrospective and therefore did not have prespecified objectives. The male patients included were younger and the majority were expatriates, while the women were older and a larger proportion represented the Qatari and Arab population. The older age is likely responsible for the higher percentage of women who made a slower recovery, but does not explain why fewer patients were offered thrombolysis acutely or the lower rates of treatment with preventative therapies. For analysis of MACE incidence, we used electronic medical records. We may have missed clinical events occurring in patients who did not go to the hospital or who may have received treatment outside the country. Finally, the population of Qatar is skewed, with a larger proportion of younger expatriate men. This may account for the higher percentage of women in the older segment of the patient population.

In summary, we present a large study from the Middle East on sex differences in the management of acute stroke. Our study shows that, compared to men, women are significantly older at presentation, experience longer delays in coming to the hospital, and are less likely to receive thrombolysis. We also showed that women are more likely to suffer in-hospital complications and make a slower recovery. Despite higher rates of disease burden and vascular risk factors, fewer women are discharged on antithrombotic, statin, or antidiabetic medications.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The study was approved by the Institutional Review Board, Hamad Medical Corporation at the Medical Research Center (MRC-01-20-1135) and the Institutional Review Board of Weill Cornell Medicine-Qatar (1932095-1/22-00016). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

HN, NA, and AS: conceptualization, design, and drafting of the manuscript. HN, MA, BK, AN, NA, and AS: acquisition, analysis, and interpretation of data and technical and administrative support. SK, SA, and AS: critical review. RS, ST, and NA: statistical analysis. All authors contributed to the article and approved the submitted version.