Stroke is the second leading cause of death worldwide 1 and is becoming increasingly common in young adults. Reference Kissela, Khoury and Alwell2 In Canada, approximately 5% of strokes occur in adults under the age of 45 years Reference Edwards, Kapral, Lindsay, Fang and Swartz3 and 15%–20% occur under the age of 60. Reference Singhal, Biller and Elkind4,5 Despite recent efforts at public education, many young adults consider stroke as a disease of elder people, which may contribute to decreased recognition of stroke symptoms and delays to seeking medical attention. Reference Shipley, Luker, Thijs and Bernhardt6 Previous studies have also reported sex differences in stroke knowledge, with young women having poor knowledge of stroke symptoms. Reference Madsen, Baird, Silver and Gjelsvik7 Hospital arrival is one of the first critical steps in early stroke management. Delayed presentation can lead to ineligibility for acute stroke treatments and worse stroke outcomes. Reference Majersik, Smith, Zahuranec, Sánchez and Morgenstern8,Reference Bunch, Nunziato and Labovitz9 Current acute stroke treatments – thrombolytic therapy with alteplase 10 and endovascular therapy (EVT Reference Goyal, Demchuk and Menon11 ) – are most effective when given early. Reference Saver12–Reference Howard, Schwamm and Donnelly16 Indeed, younger patients are more likely to receive acute treatments if they arrive by ambulance. Reference Nagaraja, Bhattacharya and Norris17
Public awareness campaigns, which include the international standard FAST (Face, Arms, Speech, Time to call 911) acronym, Reference Goldstein and Simel18,19 have been established to increase stroke awareness in Canada, yet few studies have explored ambulance utilization and hospital arrival time in young patients with stroke symptoms, and fewer have compared the prehospital behavior of men and women as well as younger and older patients with stroke symptoms. We sought to investigate age and sex differences in arrival by ambulance, time to arrival and trends over time between 2003 and 2016 in Canada. We hypothesized greater ambulance utilization and faster time to hospital arrival among older adults.
Methods
We conducted a population-based retrospective study using administrative health data from the Canadian Institute of Health Information databases. All Canadian citizens (population 37,058,856 20 ) have access to medical care under a single-payer universal healthcare system, separately administered in each province. We used the Discharge Abstract Database (DAD) 21 database to obtain administrative, demographic, and diagnoses data from health encounters in the context of acute inpatient care across hospitals in Canada, except for the province of Quebec. This includes data from a dedicated stroke Special Project (CIHI # 340), which was implemented in 2009 to collect additional core stroke performance improvement indicators. 22 Reporting to Special Project 340 is mandatory for all stroke centers in Ontario and mandated in specific or all regions by most other provinces. 23,24 In these administrative datasets, the coding of stroke and vascular risk factors has been shown to have high sensitivity and specificity. Reference Kokotailo and Hill25 The current analysis included all patients admitted to any acute inpatient care unit between the fiscal years 2003/2004 to 2015/2016 with a primary discharge diagnosis of ischemic stroke (ICD-10 codes I63 and I64, H34.1), subarachnoid hemorrhage (SAH; I60), intracerebral hemorrhage (ICH; I61), transient ischemic attack (TIA; G45, H34.0 without G45.4), and cerebral venous sinus thrombosis (I67.6, G08). Multiple stroke subtypes (ischemic, SAH, ICH, TIA, venous thrombosis) were included since, at the onset of symptoms and when calling 911, people do not yet know which stroke type they have. Demographics, stroke subtype, and arrival by ambulance were obtained from DAD database between 2003/2004 to 2015/2016, and stroke onset to hospital arrival (emergency department triage time) was obtained specifically from Project 340 data between 2009–2010 and 2015/2016. Within the administrative data, a significant increase in stroke risk factors and prevalence was observed at the age of 45 years; therefore, “young stroke” was defined as stroke occurring between 18 and 44 years of age.
Statistical Analysis
Our primary outcome was frequency of ambulance utilization and secondary outcome was time to hospital arrival. Age, sex, Charlson comorbidity index, and stroke type, arrival by ambulance and last seen normal (time from symptoms onset to hospital arrival), were examined and compared between young and older stroke patients and by sex using chi-squared tests and Wilcoxon rank-sum tests. Linear and logistic regression analyses were performed to examine trends over time in prehospital behavior and examine predictors of arrival by ambulance, respectively.
Results
Data were analyzed from 547 hospitals in DAD excluding Quebec, representing 83% of all stroke cases in Canada admitted to emergency departments between 2003 and 2016. A total of 463,310 patients (50% men) were included, of whom 17,859 (3.9%) were less than 45 years of age. Ischemic stroke was more common among older patients than younger patients (68.1% vs. 49.5%), whereas ICH and SAH were more common among the younger patients (Table 1). Younger men, compared with younger women, were significantly more likely to have an ICH (16.8% vs. 11.9%, p < 0.001) and less likely to have SAH (19.7% vs. 25.7%, p < 0.001).
Table 1: Patient characteristics
Arrival by Ambulance
Overall, 66% of patients arrived by ambulance. Older patients were more likely to arrive by ambulance than to younger patients (66.1% vs. 62.0%; p < 0.001; Figure 1). Older women were more likely to arrive by ambulance than older men (68.4% vs. 63.9%; p < 0.001); however, no differences were observed between younger men and women. Ambulance use increased significantly between 2003 and 2016 for both younger (β = 0.37, confidence interval [CI] 95% 0.05–0.69, p = 0.028) and older (β = 0.84, CI 95% 0.46–1.21, p < 0.001) patients (Figure 2) and for all groups (older men, younger men, older women, all p-values <0.05), except younger women (Figure 3). TIA patients were significantly less likely to arrive by ambulance compared with other stroke types (51.8% vs. 68.7%, p < 0.001). Ischemic stroke patients were less likely to arrive by ambulance compared with patients with hemorrhages (66.6% vs. 78.0%, p < 0.001).
Figure 1: Ambulance utilization by age and sex.
Figure 2: Ambulance utilization over time by age.
Figure 3: Ambulance utilization over time by age and sex.
Logistic regression analysis (Table 2), including age, sex, stroke type, and interaction terms, revealed that older age, male sex, and stroke type were all significant predictors of arrival by ambulance (χ 2(Reference Goyal, Demchuk and Menon11) = 21930.17, p < 0.0001). An age × sex × stroke type interaction was observed, with older females with ischemic stroke being more likely to arrive by ambulance (p < 0.001).
Table 2: Predictors of arrival by ambulance
Arrival Time
Project 340 data were available for 59,894 patients. Between 2009 and 2016, median time from stroke onset to hospital arrival time was 6.8 h (interquartile range [IQR] = 13.1). Overall, older patients arrived significantly faster than younger patients (6.8 vs. 8.3 h; Z = 7.19, p < 0.0001, Table 2). Older women arrived to hospital faster than older men (6.6 vs. 6.9 h; Z = –4.52, p < 0.0001), whereas younger women arrive significantly later than younger men (9.2 vs. 7.5 h; Z = 2.90, p = 0.004).
Discussion
Early hospital arrival is one of the most critical steps in acute stroke care. Reference Saver12 Our results suggest that younger patients are less likely to utilize ambulance services and are more likely to experience delays to hospital arrival compared with older patients. Given that the ischemic brain ages 3.6 years each hour without treatment, Reference Saver12 the median delay of 1.5 h among younger patients compared with older in time to hospital arrival is clinically significant. While ambulance use increased due to the 2006 and 2014 Canadian Heart and Stroke Foundation campaigns, the rate of ambulance use has since plateaued. 26 The gap between older and younger patients in using emergency services is increasing with time – older patients show more growth in utilization than younger ones (Figure 2), suggesting that public awareness messaging may be more successful for older patients and campaigns to improve stroke awareness and knowledge targeted toward younger patients are needed. Reference Stroebele, Müller-Riemenschneider, Nolte, Müller-Nordhorn, Bockelbrink and Willich27,Reference Hodgson, Lindsay and Rubini28 Moreover, the time to hospital arrival we observed in all groups is beyond the recommended treatment window of 4.5 h for acute thrombolytic therapy with intravenous alteplase. Reference Boulanger, Lindsay and Gubitz29 While significant improvements have been made over the past decade in arrival by ambulance, ongoing public health messaging is warranted to increase awareness of the importance of early hospital arrival.
We also observed sex differences in ambulance utilization, with younger women being least likely to use ambulance services and older women being most likely. Interestingly, there has been no increase in ambulance utilization among young women since 2003, whereas ambulance use increased in all other groups. Women overall have better knowledge of stroke signs than men, and more women know at least one FAST sign of stroke compared with men. Reference Madsen, Baird, Silver and Gjelsvik7,30 However, young women specifically may have poor knowledge of symptoms. Reference Madsen, Baird, Silver and Gjelsvik7 Previous studies examining stroke knowledge among younger and older women have reported inconsistent findings. 30,Reference Ferris, Robertson, Fabunmi and Mosca31 Ongoing public educational programs, especially targeting younger women may further improve awareness of stroke and the need to seek urgent medical attention within this population. 32
This study has several unique strengths that facilitate analysis of prehospital use by age and sex, including the large sample size, with validated population level data and high external validity. One limitation of this study is that we used administrative health databases which only include data from hospitals and provinces that record and report such data, and do not have data available for analysis from the province of Quebec (where data are collected but not available for analysis), representing roughly 20% of strokes in Canada. Reporting these data is mandatory, so there are high rates of data capture for the rest of Canada. This study included patients with stroke symptoms who received a final stroke diagnosis. However, patients with other diagnoses may also experience stroke-like symptoms and were not included in this analysis. Therefore, we cannot comment on ambulance utilization among those with stroke-like symptoms who ultimately receive other diagnoses. In addition, given the large number of patients included in this analysis, we were powered to detect even small differences in ambulance utilization among the groups.
While beyond the scope of the current analysis, future work could examine how factors such as geographical location (urban vs. rural), socioeconomic status, current residence (e.g., home, long-term care, living alone or with family), and previous exposure to and knowledge of stroke impact timing and decision to call 911.
This study highlights that younger stroke patients, especially younger women, are less likely to utilize ambulance services and seek urgent medical attention for stroke. This may in part be due to limited stroke awareness and knowledge. Given the increasing incidence of stroke among young adults, Reference Kissela, Khoury and Alwell2 and the increasing evidence of disparities in stroke management for women, 32 targeted ongoing public health messaging as well as educational campaigns are required to ensure younger adults recognize stroke symptoms and seek timely care.
Acknowledgements
The analysis for this research was funded and provided in part by the Heart and Stroke Foundation of Canada as part of their Quality of Stroke Care in Canada stroke surveillance program. We are grateful for their collaboration and support. This study was also supported by funding from the following sources awarded to RHS: Heart & Stroke Foundation Clinician-Scientist Award, the Department of Medicine at Sunnybrook and University of Toronto, and the Ontario Neurodegenerative Disease Research Initiative through the Ontario Brain Institute (an independent, nonprofit corporation funded partially by the Ontario Government – the opinions results and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred).
Conflict of Interest
Dr. Swartz reports grants from Heart & Stroke Foundation Clinician-Scientist Award, grants from Ontario Neurodegenerative Disease Research Initiative through the Ontario Brain Institute, grants from Department of Medicine at Sunnybrook and University of Toronto, during the conduct of the study. Dr. Yu reports grants from Heart and Stroke Foundation of Canada, grants from Canadian Institutes of Health Research, grants from Academic Health Sciences Centres of Ontario, outside the submitted work. Dr. Lindsay works for the Heart and Stroke Foundation of Canada. The other authors have no conflicts of interest to declare.
Statement of Authorship
RHS and AK contributed to the literature search; RHS, MPL, AYXY, and AK designed the study and interpreted the data. RHS, CG, and AK analyzed the data. AK, RHS, MPL, CG, AYXY, SC, and PRV contributed to the writing of the manuscript and critical review and approval of the final manuscript.
