Racial and ethnic differences in access to care and treatment in patients with suspected acute stroke: A retrospective, observational, cohort study

Background: Data regarding unequal diagnostic and therapeutic access in patients with acute stroke based on ethnicity and race are inconclusive in Europeans. The objectives of our study were to evaluate the effect of race/ ethnicity on access to acute stroke care and treatments and outcomes. Methods: In this retrospective cohort study, we enrolled adult patients admitted to the emergency department of a comprehensive stroke center for suspected stroke. Based on race/ethnicity, patients were divided into two main groups: Western European Whites (WEW) and non-Western European Whites (nWEW). We also divided the nWEW group into four subgroups based on the Office of Management and Budget classification of human races and ethnicities (White-Others, Hispanic, Asian, Black). Univariate comparisons and logistic regression analyses were also performed. Results: 9167 patients were enrolled in the study: 582 in the nWEW and 8585 in the WEW group. Patients with ischemic stroke in the nWEW group were significantly younger than those in the other group ( p < 0.001). Once adjusted for possible confounders, belonging to the nWEW group was found to be an independent predictor of a lower likelihood of receiving revascularization treatments ( p = 0.006), regardless similar onset-to-door times. There were no differences in stroke outcomes and prevalence of stroke mimic diagnosis between the groups. Conclusions: Racial/ethnic disparities in healthcare represent a challenging issue, even in universal healthcare systems, that should be addressed promptly through education campaigns of healthcare personnel and implementation measures, such as integrating readily available interpreter staff for medical emergencies.


Introduction
Stroke is a leading cause of mortality and disability worldwide [1].Despite its high prevalence across countries, stroke does not affect all human races in the same way and could be defined as a "racial inequitable" disease [2].
Race influences stroke etiopathogenesis because many modifiable and non-modifiable risk factors for stroke are more prevalent in African-Americans and Hispanics than in Whites and Asians [2].As a direct consequence, stroke incidence is more prevalent in Blacks and Hispanics than in White people [3,4].On the other hand, access to revascularization treatment [5] does not appear to be guaranteed to ethnic minorities, although in recent years stroke care limitations appear to be reduced [6].
As a result, stroke outcomes are influenced by ethnicity, with higher stroke mortality in Blacks than in Whites, with a downward trend with increasing age of the subjects [4].Conversely, cerebral haemorrhage is more prevalent in Black and Asian populations than in Whites [7,8], but it is associated with a better prognosis in racial/ethnic minorities [9].
Race also influences the rate of admission to the Emergency Department (ED) for stroke-mimicking conditions, which are less frequent in Hispanics and Asians [10], but more frequent in Blacks [11] than in Caucasian patients.
However, most studies were conducted in the United States of America, where the ethnic and racial composition is different from Europe and Italy, where epidemiological studies investigating the impact of race/ethnicity on stroke features, management, and outcomes are lacking.Moreover, the different organization of the health systems could play a role in limiting access to timely and appropriate medical treatments based on race and ethnicity.
Italy is a country in which, similar to other European realities, in recent decades, there has been a strong increase in immigration rates, particularly those coming from eastern European countries, so much so that today people with foreign citizenship account for 9 % of the total population [12].Despite this, systematic racism against ethnic/racial minorities in Italy represents an important problem, as evidenced by the existence of large inequalities in the educational status, socioeconomic status, overqualification, and housing conditions of the foreign population [13].Although the universal, tax-funded healthcare system that is in force in Italy should ensure access to urgent care and treatments for all, there are no direct studies investigating this issue from a racial/ ethnic perspective.A recent scoping review highlighted that individuallevel racism plays a major role in driving health inequalities, while evidence of racism on institutional and structural levels remains extremely scarce, even in other European countries [14].
Based on these premises, the primary objective of our study was to evaluate the effect of race/ethnicity on access to care and treatment of patients with acute stroke in our comprehensive stroke centre in Rome.Second, we evaluated the effects of race and ethnicity on stroke outcomes.Finally, we investigated the racial/ethnic differences in the rate of ED admission for stroke mimics.

Study design and population
This was a single-center, retrospective, observational, cohort study conducted on adult patients admitted to the ED of a comprehensive stroke center, from January 1, 2015, to December 31, 2022, for a suspected diagnosis of ischemic or hemorrhagic stroke and, for this reason, undergoing clinical evaluation by neurologist experts in cerebrovascular diseases.Our comprehensive stroke centre is, accordingly to the "hub & spoke stroke model" [15], the reference hospital for the entire north portion of the Lazio region.Because of the extension of the area covered by its stroke network and the fact that the hub-and-spoke model is widespread in many Italian regions, we can assume that our population is representative of that present in Italy and other reference stroke hospitals.
Race and ethnicity were self-reported by the study participants or, in case of diminished capacity, by their caregivers at the time of the triage assessment [16].Race categories were defined by investigators based on the US Office of Management and Budget's (OMB) Revisions to the Standards for the Classification of Federal Data on Race and Ethnicity [17].Therefore, we considered the following racial/ethnic categories: Hispanic White, Black, and Asian.Since no patients self-identified themselves as belonging to the group "Native Hawaiian or other Pacific Islander", we did not consider this racial subgroup.Finally, to better reflect the European socio-cultural context, we further divided the group of White patients in "Western European Whites" (WEW) and "Other Whites" (OW).This stratification was based on the peculiar economic/social composition of European countries, characterized by the systemic racism of Western Europeans against people from Eastern Europe due to the cultural and political differences among these geopolitical blocks and the relatively recent rise in East-to-West migration [18].Furthermore, there are large differences in terms of life expectancy, standardized mortality rates for cardiovascular diseases, lifestyle behaviours, and many more, between Eastern and Western European countries [19].Because individual racial/ethnic subgroups had a small sample size, we decided to assemble all racial/ethnic categories, except that of WEW, into a single group, called non-Western European Whites (nWEW), to investigate possible differences in management and outcomes between the predominant racial group and ethnic/cultural minorities.
Patients who met the following criteria were included in the study: 1) presentation to the ED for a suspected stroke, 2) clinical evaluation during their ED stay by a physician expert in cerebrovascular diseases, 3) adult age (≥18 years).Exclusion criteria were: 1) pregnancy, 2) insufficient or inadequate clinical information to define discharge diagnosis, 3) direct transfer from the ED to another hospital.
Due to the retrospective nature of the study and anonymous data collection, patients' informed consent was waived.This study was conformed to the principles of the 1964 Declaration of Helsinki and its later amendments.The research protocol was approved by the ethics committee of Fondazione Policlinico Universitario "A Gemelli" IRCCS-Rome (prot.number#0025817/22).This study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies.

Data collection
Clinical and demographic data were anonymously and retrospectively collected by electronic medical record screening by four investigators who were highly experienced in stroke management (J.D.G., I.S., P.A.R., and S.B.).The following data were collected for each included patient: sex, age, country of origin, racial/ethnic belonging, systolic and diastolic blood pressure, heart rate (HR), peripheral oxygen saturation (SaO2), body temperature, main symptoms at the time of ED admission as defined by triage personnel, comorbidities based on patient history, and Revascularization Treatments (RTs).The time elapsed from the onset of symptoms to ED arrival (Onset to Door Time, ODT) was stratified into three categories: "<6 h", "6-24 h", and ">24 h".
Based on the income of the origin country of the patients, we divided the study population into two groups: "High income" vs "Others", including in the second group all the countries classified as "low", "lower-middle", and "upper-middle" income according to the 2018 Update of the World Bank classification [20].We chose the 2018 update because we believe that it is more representative of our patient population enrolled between 2015 and 2022.
The mode of patient arrival to the ED was classified as "Emergency Medical Service" (EMS) or "walk-in".
For each included patient, the main discharge diagnosis was categorized into one of three possible options: stroke, stroke mimic, or Transient Ischemic Attack (TIA).Stroke was defined as the sudden onset of a new focal neurological deficit of vascular origin at a site consistent with the territory of a major cerebral artery, and was categorized as ischemic or hemorrhagic.Transient Ischemic Attack was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia without acute infarction.Stroke mimics were defined as patients who presented to the ED with stroke-like symptoms and were admitted by the personnel of the triage with a diagnosis of "suspected stroke"; however, after work-up, a stroke or TIA was not determined.
The Charlson Comorbidity Index (CCI) was calculated for each study participant based on the summary of patients' comorbidities, and the National Institute of Health Stroke Scale (NIHSS) was used to determine symptom severity at admission for all patients who were diagnosed with stroke (both ischemic and hemorrhagic) at discharge.

Outcome measures
We considered all-cause in-hospital mortality as the primary outcome measure in this study.The secondary outcome measures were hospitalization, hospitalization in the neurological department, need for mechanical ventilation, tracheostomy, and length of in-hospital stay (days).

Statistical analysis
Qualitative variables are expressed as absolute and relative percentage frequencies.The Gaussian distribution of the study variables was assessed using the Shapiro-Wilk test.Quantitative variables are reported as median and interquartile range (IQR).Comparisons among groups were performed using the χ2-test or Fisher's exact test for qualitative variables and the Mann-Whitney U test or Kruskal-Wallis test for numerical variables, as appropriate.We then performed multivariate logistic regression analyses, including variables that obtained a significant p-value (p < 0.05) in univariate comparisons and those selected by expert opinion.Correlations among variables were investigated using Spearman's correlation coefficient.All statistical analyses were performed using the Statistical Package for Social Science (SPSS) software v26® (IBM, Armonk, NY, USA).

Whole study population
A total of 518,195 patients were admitted to the ED of our polyclinic, and 10,332 (1,9 %) were evaluated for suspected stroke by a physician expert in cerebrovascular diseases.Of them, 1165 subjects met at least one exclusion criterion.The final study population included 9167 patients.In this cohort, 4677 patients (51.0 %) had a discharge diagnosis of stroke (4070 ischemic and 607 haemorrhagic), 882 (9.6 %) were diagnosed with TIA, and 3608 (39.4 %) were diagnosed with a strokemimicking condition.5559.
Several demographic differences were observed between the groups.Patients in the WEW group were significantly older than those in the other group (p < 0.001) and all came from a high-income country (p < 0.001).The male/female ratio, mode of ED arrival, and time elapsed from symptom onset did not differ significantly between racial/ethnic subgroups.However, many patients' comorbidities, neurological symptoms at onset, and physiological parameters at admission differed between the WEW and nWEW groups (Table 1).With the exception of the rate of hospitalization in the neurological department, which was higher in WEW patients (p = 0.011), in-hospital management was similar between the groups.The proportion of in-hospital deaths was higher in the WEW group (p < 0.001) than in the nWEW group.
Significant differences were also observed in the discharge diagnoses of the included patients (p < 0.001).Brain haemorrhages were more frequent in the WEW group, whereas ischemic strokes, stroke-mimicking conditions, and TIAs were more frequent in the racial/ethnic minority group.All the data are presented in Table 1.Details on demographic and clinical characteristics and stroke management of each individual racial/ethnic subgroup, are provided in Supplementary Table 1.

Ischemic stroke patients
We then considered the subgroup of 4070 patients with a discharge diagnosis of ischemic stroke, evaluating racial/ethnic differences in this specific sub-population.Also in this group, WEW patients constituted the vast majority of the population (3809, 93.6 %) and were significantly older (p < 0.001) than the others.The male/female ratio differed between the groups, females being more represented in the WEW group (p = 0.033).
The severity of stroke symptoms at onset was similar between the groups, as detected by the similar median NIHSS scores.Sensory impairment, dizziness, and headache were more frequent in nWEW than in WEW patients (p = 0.001, p < 0.001 and p < 0.001 respectively).The CCI was higher in WEW patients (p < 0.001), who were more frequently affected by peripheral artery disease (p = 0.003), major neurocognitive disorder (p = 0.006), COPD (p = 0.003), and solid cancer (p = 0.044).
Although nWEW patients tended to use EMS more frequently than WEW patients in reaching the ED, the latter had a shorter median ODT time.However, these differences were not significant (p = 0.054 and p = 0.066, respectively).As regards in-hospital management, it can be appreciated that racial/ethnic minority patients were classified less frequently at triage with "emergency" or "urgency" codes compared to others (p = 0.031).
The rate of RTs administration and stroke outcomes did not differ between the groups, with the exception of the rate of hospitalization in the neurology department (p = 0.009), which was higher in the nWEW group, and in-hospital death was more frequent in the WEW group (p < 0.001).For more details, please refer to Table 2.
A detailed description of the subgroup of patients with a discharge diagnosis of ischemic stroke divided by each individual racial/ethnic group is provided in Supplementary Table 2.

Predictors of revascularization treatments
Among the ischemic stroke patients, 946 underwent RTs (23.2 %).In the univariate comparison, no differences were found in the rate of RTs between the nWEW and WEW groups (p = 0.246).Patients who underwent RTs were significantly younger than those who did not undergo RTs (p = 0.001).Non-significant differences were found among physiological parameters, with the exception of median the HR, which was higher in non-treated patients (p < 0.001).Main symptoms at ED admission were significantly different between the groups: speech disorders (p < 0.001) were more frequent in patients undergoing RTs, while sensory impairment (p < 0.001), headache (p < 0.001), dizziness (p = 0.017), epileptic seizure (p = 0.003), and syncope (p = 0.017) were more frequent in non-treated patients.As expected, treated patients had a higher median NIHSS score (p < 0.001).
With regard to stroke management, patients undergoing RTs had longer hospital stays (p = 0.012) and were more frequently hospitalized   (p < 0.001), particularly in the neurology department (p < 0.001).
Although treated patients were more frequently subjected to mechanical ventilation and tracheostomy (both p < 0.001), no difference was found in the rate of in-hospital death.For more details, please refer to Table 3.
After adjusting for demographic and clinical-physiological parameters, mode of ED arrival, and ODT, we found that belonging to the nWEW group was an independent predictor of not undergoing RTs (p = 0.006) (Table 3).

Predictors of in-hospital death
Considering the subgroup of patients with a discharge diagnosis of ischemic stroke, WEW patients presented a higher rate of in-hospital death (p < 0.001).Moreover, coming from a high-income country (p < 0.001), and several demographic, clinical, and physiological parameters were associated with higher mortality (Table 4).Additionally, deceased patients had longer ODT (p < 0.001), arrived at the ED more frequently with EMS (p < 0.001), had a higher overall comorbidity burden (p < 0.001), had a higher NIHSS score (p < 0.001), and were less frequently subjected to RTs, although this difference was not statistically significant (p = 0.086).
In the multivariable logistic regression adjusted for parameters that differed significantly between the groups in the univariate comparison and for RTs, only age (p = 0.031) and NIHSS score at onset (p < 0.001) were independent predictors of in-hospital death.We decided not to consider the origin from a high-income country in the adjusted model because this parameter had a strong correlation with racial/ethnic belonging (Spearman's rho = 0.947, p < 0.001) (Table 4).

Stroke and TIA vs mimics
To evaluate the effect of race/ethnicity on ED visits for stroke mimics diagnosis, we performed an analysis comparing all the patients with a discharge diagnosis of ischemic/haemorrhagic stroke and TIA (5559/ 9167; 60.6 %) to the group of patients with a discharge diagnosis of a stroke-mimicking condition (3608/9187; 39.4 %).
In this comparison, the stroke mimic patients were significantly younger (p < 0.001) and more frequently female (p < 0.001) than stroke patients.No racial/ethnic differences were found between patients based on discharge diagnosis.Many physiological parameters, symptoms at ED admission, and comorbidities differed between the two groups.Please refer to the Supplementary Materials (Table S3).

Discussion
In this study, no difference was found in the rate of revascularization treatments for acute stroke between Western European Whites and non-Western European Whites.However, when adjusting for all relevant confounders, racial/ethnic minority patients were nearly two times less likely to receive RTs than WEWs, despite similar onset-to-door times.Despite this inequality, race/ethnicity was not associated with worst inhospital outcome after acute stroke, likely because of the younger median age of the nWEW group.
Unequal access to RTs for racial minorities has been widely described in the United States [6,21], where the black race is the least subjected to revascularization treatments [6].Unequal access to treatment has also been described in Europe [22], where a universal healthcare system should guarantee better uniformity of treatment than in other countries with an insurance-based healthcare system.One of the main causes may certainly be the low socio-economic status and, consequently, the low level of education that exposes racial/ethnic minorities to ignoring information campaigns both on the early symptoms of stroke and on the importance of promptly going to the ED [23].However, in our study, the difference in treatment rate persisted even when adjusted for ODT and mode of ED arrival, suggesting that the cause of this inequality should be sought in the in-hospital path and not in the pre-hospital phase.
To analyse the possible causes, it should be considered that there is a close link between being from ethnic minorities and poor knowledge of local and English language, particularly in recently immigrated people [24].In immigrants, language barriers may play a crucial role in limiting access to care, both in terms of the health literacy of patients and their relatives [25] and in terms of physicians' understanding of clinical history and symptoms.A Danish study by Mkoma et al. [26] strengthened this hypothesis, finding a lower chance of receiving RTs among immigrants than among Danish-born residents, a finding that was more pronounced when only non-Western immigrants were considered in the analysis.Interestingly, in our study, RTs were more frequent in subjects with speech disorders, that may be underdiagnosed in people with language barriers.Although previous studies conducted in the United States [27] and Canada [28] have reported no differences in access to acute stroke care based on patients' preferred language, in Italy, the limited development of health policies for migrants regarding access to health services [29] and the poor knowledge of foreign languages by healthcare professionals [30] make the language barrier a crucial factor for access to treatment of time-dependent diseases such as stroke.Furthermore, educational campaigns for the early recognition of stroke symptoms have been conducted in Italian, limiting their comprehensibility to non-Italian speakers [31].
Regarding stroke outcomes, we found that WEW had a higher incidence of in-hospital death compared to the racial/ethnic minority group, largely attributable to the older age of the former group.However, after adjusting for possible confounders, no effect of race/ethnicity on the incidence of in-hospital death was found, in contrast to some studies demonstrating an increased death rate among racial minorities [4,32].On the other hand, our results are in line with those of other studies describing similar mortality rates from stroke among different races [33,34].These seemingly discordant data relate to the different national health systems and different policies of immigrants' integration where the studies were conducted.
Moreover, we found a different prevalence of cardiovascular risk factors and other comorbidities among racial/ethnic groups, which could be largely explained by the older age of the WEW patients.As expected, similar findings were observed when considering only patients with a discharge diagnosis of ischemic stroke, confirming previous literature demonstrating that racial/ethnic minority groups tend to present with stroke at younger ages than Whites [4].
Regarding the relationship between stroke mimics and race/ ethnicity, some authors have reported a lower prevalence of stroke mimics in racial/ethnic minority patients compared to Whites [10,35], a finding that has not been confirmed by our study.Further studies are required to clarify this point.

Limitations
The main limitation of this study is its single-centre, retrospective design, which prevents the generalization of the results to the overall stroke population.Second, no information about immigration status, educational level, and languages spoken by the included patients was considered in the analysis.Although we found no significant differences in the outcomes of stroke patients based on race/ethnicity, we have no long-term data on this parameter.Additionally, we grouped all patients belonging to racial/ethnic minorities into one group to reduce possible biases related to the small sample size of each racial subgroup.Finally, we did not have data on the overall time spent living in Italy by the patients included in the study, thus limiting the possibility of exploring the effects of cultural factors on the study outcomes.

Conclusions
Racial and ethnic disparities in healthcare may be a critical issue, even in universal healthcare systems such as in many European healthcare systems.In our study, we highlighted unequal access to RTs  in non-Western European Whites, which persisted after adjusting for ODT and mode of ED arrival, suggesting that the causes of these inequalities should be sought in deficiencies in the hospital management phase.It is therefore a challenge that public health systems must face through the training of health personnel and the implementation of measures aimed at limiting this inequality, such as the hiring of multilingual interpreters who can be contacted 24 h a day in the context of emergencies.Further multicenter studies are needed to strengthen the evidence emerging from this study and to clarify the reasons for inequalities in stroke management.Declarations.

Fig. 1 .
Fig. 1.An illustration depicting the geographic origin of included patients.Percentages refer to the number of patients from each continent compared to the total number of study subjects.

Table 1
A descriptive table reporting the demographics, clinical characteristics, discharge diagnoses, and outcomes of the entire study population and the univariate comparison of these parameters between the WEW and nWEW groups.

Table 2 A
summary of the characteristic of the ischemic stroke population and a comparison between the WEW and the nWEW groups.

Table 3
Unadjusted and adjusted comparisons between patients with a discharge diagnosis of ischemic stroke who underwent revascularization treatments and those who did not receive acute stroke therapy.All categorical variables are reported as number and percentage (%), numerical variables are reported as median (IQR).Abbreviations: ED, Emergency Department; bpm, beats per minute; SaO2, peripheral oxygen saturation; AMI, Acute Myocardial Infarction; CAD, Coronary Artery Disease; TIA, Transient Ischemic Attack; COPD, Chronic Obstructive Pulmonary Disease; HIV, Human Immunodeficiency Virus; OR; Odds Ratio; CI, Confidence Interval.

Table 4
Univariate and multivariate comparisons between patients who survived and died during hospitalization.