Abstract
Objective
To analyze the geographic variation in characteristics and treatment processes of patients with acute ischemic stroke (AIS) in coastal, island, and inland regions.
Methods
We conducted a retrospective, cross-sectional analysis of data from patients with AIS in southeastern China. We collected demographic and clinical information, including the time from stroke onset to treatment for those receiving reperfusion therapy, using a time-tracking table.
Results
Among 8069 patients with AIS, 26.6% received reperfusion therapy, with a higher proportion undergoing endovascular therapy in maritime hospitals than in inland hospitals (14.2% vs. 6.7%). Maritime hospitals had a higher prevalence of atrial fibrillation (15.1% vs. 11.9%) and cardioembolism (17.2% vs. 13.6%) than inland hospitals. Patients in maritime hospitals had shorter in-hospital processing times than those in inland hospitals (39 vs. 46 minutes). Island hospitals showed different patterns, with a shorter time from stroke onset to emergency room arrival (80 vs. 120 minutes) but a longer in-hospital process time (51 vs. 36 minutes), than coastline hospitals.
Conclusions
Our study suggests geographic variation in AIS characteristics and treatment processes across southeastern China, emphasizing the need for region-specific strategies. These findings are essential for tailoring public health policies and guidelines to improve stroke outcomes in various regions.
Keywords
Introduction
Stroke is a leading cause of death and disability worldwide, accounting for considerable direct and indirect costs to healthcare systems and societies. 1 Ischemic stroke represents approximately 80% of all stroke cases. 2 Reperfusion therapy, including intravenous thrombolysis (IVT) and endovascular therapy (EVT), is currently the most promising treatment for acute ischemic stroke (AIS).3,4 However, because of concerns about complications and limitations in medical resources, a large portion of eligible patients in China have not been able to receive reperfusion therapy. 5
Understanding the patterns of disease burden is critical for guiding public health decisions. The 2016 Global Burden of Disease Study showed notable spatial variability in cardiovascular disease and its major subcategories, including ischemic heart disease, hemorrhagic stroke, and ischemic stroke, in China. 6 This study suggested that economically developed coastal provinces tend to have a lower burden of cardiovascular disease. Similarly, the Global Burden of Disease study highlighted geographical disparities in stroke burden trends in the United States. 2 This study showed that the stroke incidence has decreased in older adults (50–74 years) in coastal areas, while increasing in younger populations (15–49 years) in the southern and midwestern regions. Recent studies have examined these trends. In 2022, a study summarized cardiovascular health in China, and emphasized the effect of urbanization and lifestyle changes, with a notable increase in disease prevalence in urban areas compared with rural areas. 7 In 2024, another study analyzed the stroke incidence in the United States, and showed improvements in stroke management and outcomes in urban centers relative to rural areas. 8
Although there have been many studies on ischemic stroke, research focusing on the differences between maritime and inland regions is limited, with little known about metrics related to reperfusion therapy processes. Additionally, unique island regions might show disease patterns that differ from those of coastal areas, which is a topic that has not been previously investigated. Therefore, in the current study, we analyzed the characteristics of patients with ischemic stroke in different hospitals from coastal, island, and inland regions in southeastern China to examine potential disparities in the context of reperfusion therapy and stroke management.
Methods
Patients and data collection
We conducted a retrospective, cross-sectional analysis of a database for consecutive patients with AIS, as confirmed by non-enhanced head computed tomography or magnetic resonance imaging. The patients were from three stroke centers in southeastern China, and the study spanned the period from November 2019 to November 2023. All patients’ details were de-identified to ensure anonymity, in accordance with ethical standards. The reporting of this study conforms to the STROBE guidelines. 9 We extracted demographic, clinical, and imaging data, including age, sex, and comorbid conditions, such as hypertension, diabetes mellitus, atrial fibrillation, previous stroke or transient ischemic attack (TIA), and the current smoking status. Additionally, we collected information on prior use of anticoagulants, antiplatelets, or statins, as well as the National Institutes of Health Stroke Scale (NIHSS) score at admission, infarct location, stroke etiology, the time from stroke onset to treatment in those who received reperfusion therapy, and the occlusion site in patients with large vessel occlusion (LVO) at the time of admission. We implemented a standardized data extraction process from electronic medical records to ensure consistent and accurate data collection, reducing recall bias in the process. This study received approval for a waiver of ethical approval and informed consent from the local human ethics committees at all three hospitals, and was conducted in accordance with the principles outlined in the Declaration of Helsinki. 10 The waiver of individual consent for this retrospective analysis helped reduce consent-related bias because all eligible patients were automatically included without selection on the basis of their ability or willingness to consent.
Reperfusion treatment and time-tracking table
Clinicians recommend different reperfusion therapy approaches depending on patients’ needs, which may include IVT alone, EVT alone, or a bridging therapy that combines both IVT and EVT. A suitable mismatch profile might guide the choice of reperfusion therapy in patients who undergo multimodal imaging beyond the conventional treatment window.11–13 Variations in individual clinician’s decisions for reperfusion therapy exist, though these are likely minimal because of national guidelines. The patient’s economic status and insurance coverage may also influence treatment choices, potentially reflecting regional differences, which is one aspect analyzed in this study.
To monitor the efficiency of the procedures, we prospectively recorded the start and end times of each step using a dedicated time-tracking table. The recorded times included the duration from the onset of symptoms of stroke to arrival at the emergency room (onset to door time), from emergency room arrival to treatment (door to needle or puncture time), and from the onset of symptoms to treatment (onset to needle or puncture time). The tracking table was completed within 24 hours after the procedure and securely managed by a specifically designated individual.
Statistical analysis
Data are presented as the median (interquartile range [IQR]) or number (%). The independent samples t-test or Mann–Whitney U test was used to compare continuous variables, while the chi-square test or Fisher’s exact test was used to compare dichotomous variables between groups. Statistical significance was set at a p value <0.05. All statistical analyses were performed with IBM SPSS software package, version 23.0 (IBM Corp., Armonk, NY, USA).
Results
Patients
During the study period, 8069 patients with AIS were enrolled from three stroke centers in Southeastern China (Figure 1). Among them, 3359 (41.6%) were treated at inland hospitals, while 4710 (58.4%) were treated at maritime hospitals. Among those treated at maritime hospitals, 204 (4.3%) patients were from island-based hospitals. Among the included patients, the median age was 69 years (IQR 60–78 years), with 3157 women (39.1%). The median baseline NIHSS score was 3 (IQR 1–6). Overall, 2147 (26.6%) patients received reperfusion therapy.
Flowchart showing the distribution of patients with acute ischemic stroke across hospitals in different regions and the details of their reperfusion therapy.
Comparison of patients with AIS between maritime and inland hospitals
Table 1 shows comparison of the characteristics of patients with AIS in maritime and inland hospitals. There was no significant difference in age or sex between patients in maritime hospitals and those in inland groups. The proportion of patients with hypertension or current smoking was also similar between these groups of patients. However, patients in maritime hospitals had a significantly higher prevalence of diabetes mellitus and atrial fibrillation than those in inland hospitals (both p < 0.001). However, patients in inland hospitals more frequently had ischemic stroke or TIA (p < 0.001), and more frequent use of prior antiplatelets (p = 0.001) and statins (p < 0.001) than those in maritime hospitals. Despite differences in the prevalence of atrial fibrillation, a low proportion of patients in both types of hospitals had prior anticoagulant use, with no significant difference between them. Patients in maritime hospitals had a significantly higher percentage of patients with cardioembolism and a higher NIHSS score at admission than those in inland hospitals (both p < 0.001).
Comparison of patients with acute ischemic stroke between maritime and inland hospitals.
Data are the mean ± standard deviation, n (%), or median (range).
TIA, transient ischemic attack; NIHSS, National Institute of Health Stroke Scale.
The proportion of patients receiving reperfusion therapy was similar between maritime and inland hospitals (Table 2). However, the proportion of patients who underwent EVT was higher in maritime hospitals than in inland hospitals (p < 0.001). Among patients who received reperfusion therapy, those in maritime hospitals had a significantly longer time from stroke onset to arrival at the emergency room, but the in-hospital process took less time, than those in inland hospitals (both p < 0.001). There was no significant difference in the site of occlusion for LVO between patients in the two types of hospitals.
Comparison of reperfusion therapy data in patients with acute ischemic stroke between maritime and inland hospitals.
Data are n (%) or median (range).
IVT, intravenous thrombolysis; EVT, endovascular thrombectomy; LVO, large vessel occlusion.
Comparison of patients with AIS between island and coastline hospitals
Table 3 shows comparison of the characteristics of patients with AIS in island and coastline hospitals. Patients in island hospitals were more likely to be men (p = 0.040) and tended to be younger (p = 0.065) than those in coastline hospitals. Patients in island hospitals also had a lower prevalence of comorbid hypertension (p < 0.001), diabetes (p = 0.001), and current smoking (p < 0.001), but a higher prevalence of atrial fibrillation (p = 0.004). In contrast, patients in coastline hospitals had a higher prevalence of prior ischemic stroke or TIA and more frequent use of statins (p = 0.011), but not antiplatelets. Despite differences in the prevalence of atrial fibrillation, both groups of patients had a low proportion of prior anticoagulant use, with no significant difference between them. Island hospitals had a higher percentage of patients with cardioembolism (p = 0.046) and patients had higher NIHSS scores upon admission than those in coastline hospitals (p < 0.001).
Comparison of patients with acute ischemic stroke between island and coastline hospitals.
Data are the mean ± standard deviation, n (%), or median (range).
TIA, transient ischemic attacks; NIHSS, National Institute of Health Stroke Scale.
The patients in island hospitals did not receive in-hospital EVT. Table 4 shows comparison of IVT data between patients with AIS in island hospitals and those in coastline hospitals. Among those who received IVT, patients in island hospitals had a shorter time from stroke onset to arrival at the emergency room, but the in-hospital process took longer, than those in coastline hospitals (both p < 0.001).
Comparison of intravenous thrombolysis data in patients with acute ischemic stroke between island and coastline hospitals.
Discussion
In this study, we examined the similarities and differences in the characteristics of patients with AIS from various geographic locations in southeastern China, with a focus on the effect of coastal and island environments. Patients with AIS treated at maritime and inland hospitals showed differences in vascular risk factors and stroke etiology. A notable trend was that the prevalence of cardioembolic stroke increased progressively from inland hospitals to coastline and island hospitals. This finding was accompanied by a corresponding rise in the baseline severity of stroke, in line with a higher proportion of patients with atrial fibrillation. In patients who received reperfusion therapy, those treated at maritime hospitals had a higher proportion of EVT than those treated at inland hospitals, indicating that these patients often had a longer travel time to the hospital but shorter in-hospital process times. These differences may be associated with regional traffic conditions and the distribution of medical resources.
A national and province-level study on the burden of cardiovascular disease from 1990 to 2016 in China showed that the number of prevalent cases has doubled since 1990, reaching nearly 94 million in 2016. 6 Coastal provinces with higher economic development appeared to have a lower cardiovascular disease burden in China. Similarly, in the United States, older adults (50–74 years) experienced a decrease in the incidence of ischemic and hemorrhagic stroke in coastal areas. 2 Our study, which was a cross-sectional analysis, focused primarily on data from southeastern China and involved patients who had already experienced AIS. We found that the proportion of recurrent stroke was significantly lower in patients from maritime hospitals than in those from inland hospitals. We also observed that regardless of the geographical location, the proportion of patients with prior antiplatelet and statin use was lower than the proportion of those with prior ischemic stroke or TIA, with statin use even lower than antiplatelet use. This finding suggests that there is room for improvement in secondary prevention. Additionally, our study indicated that the proportion of patients with diabetes was higher in maritime hospitals than in inland hospitals. A study in South Korea that used health insurance claim data to investigate the burden of disease in coastal areas showed that diabetes mellitus was the leading specific disease contributing to years lived with disability per 100,000 population. 14 In our study, the prevalence of atrial fibrillation was significantly higher in patients from maritime hospitals than in those from inland hospitals, but prior anticoagulant use was equally low in both groups. A community-based survey of 47,841 adults (aged 45 years and older) across seven geographic regions of China from 2014 to 2016 showed that only 6.0% of patients with high-risk atrial fibrillation received anticoagulation therapy. 15 In our study, the prevalence of cardioembolism in patients from maritime hospitals was significantly higher than that in those from inland hospitals, which is consistent with the higher prevalence of atrial fibrillation. Consequently, the baseline severity of stroke was slightly higher in patients from maritime hospitals than in those from inland hospitals.
Among the patients who received reperfusion therapy, those from maritime hospitals were more likely to undergo EVT than those from inland hospitals. There are two possible explanations for this finding. First, the higher proportion of cardioembolism in patients in maritime hospitals than that in those in inland hospitals might indicate a greater incidence of LVO. Second, there are relatively better economic conditions in coastal areas than in inland areas because EVT is still relatively expensive under China’s healthcare system. Patients in maritime hospitals had a longer time from stroke onset to arrival at the emergency room, which was likely due to traffic conditions and hospital distribution. However, the time from arrival at the emergency room to thrombolysis or puncture was shorter in patients in maritime hospitals than in those in inland hospitals. This finding suggests that maritime hospitals have a better in-hospital process, resulting in smoother operations.
A small proportion of patients were treated at island hospitals, and we found that they differed in several ways from those treated at coastline hospitals. Patients at island hospitals had a higher proportion of male sex and a lower prevalence of comorbidities, such as hypertension, diabetes, and current smoking, but a higher prevalence of atrial fibrillation than those in coastline hospitals This finding of patients at island hospitals was associated with a higher proportion of those with cardioembolic stroke and greater baseline stroke severity. Interestingly, a lower proportion of patients in island hospitals had prior stroke than those in coastline hospitals but they had a relatively high rate of prior antiplatelet drug use. This finding might be due to the application of primary prevention for cardiovascular diseases. However, because of the low use of statins, the observed pattern may reflect inconsistencies in primary and secondary prevention practices. Furthermore, patients in island hospitals had a shorter time from stroke onset to arrival at the emergency room than those in coastline hospitals. This finding is likely due to the island’s unique geography, which makes transportation to outside hospitals challenging but ensures close proximity to the local hospital. However, patients in island hospitals had a longer time from arrival at the emergency room to thrombolysis than those in coastline hospitals, indicating that stroke management processes within the hospital still require further optimization.
The reasons for geographic variations in the characteristics of AIS are complex. High temperatures during hot months may trigger first-ever strokes, while low air pressure can lead to depression and increased blood pressure, potentially exacerbating this effect. 16 Air pollution, particularly short-term increases in sulfur dioxide, nitrogen dioxide, and particulate matter 10 µm or less in diameter, could be major triggers for stroke-related hospitalizations. 17 Therefore, soil chemistry and physical properties could promote the growth and survival of microorganisms that may predispose individuals to stroke. A study from the South Carolina coastal area showed that the depth to the water table, drainage class, hydric rating (hydric soils), and pH (strongly acidic) were related to the stroke rate. 18 Dietary factors such as oily fish intake may reduce the progression of white matter hyperintensities of presumed vascular origin owing to the high content of omega-3 polyunsaturated fatty acids and other nutrients. 19 Although there is no direct evidence that oily fish intake reduces the stroke incidence, it could contribute to geographic differences in stroke etiology. In addition to natural environmental factors, we must also consider variations in transportation, healthcare resource distribution, physicians’ attitudes, and public education. These factors may influence the implementation of reperfusion therapy and primary/secondary prevention of ischemic stroke across different regions.
To address the geographic variations in stroke characteristics and outcomes identified in our study, practitioners should tailor their approaches on the basis of regional factors. In maritime and island hospitals, where there is a higher prevalence of atrial fibrillation and cardioembolic stroke, emphasis should be placed on early detection and aggressive management of atrial fibrillation with anticoagulation. Improving public education on stroke symptoms and prompt medical attention are crucial, particularly in areas facing transportation challenges. Additionally, optimizing in-hospital processes to ensure timely reperfusion therapy is recommended, especially in island hospitals with longer door to needle times. A consistent application of primary and secondary prevention measures, such as antiplatelets and statins, should be adapted to regional demographics to improve stroke outcomes. These recommendations could be integrated into clinical practice guidelines by emphasizing the need for region-specific strategies for stroke management and prevention. Guidelines should incorporate recommendations for enhanced public education, timely treatment, and optimized in-hospital procedures. Furthermore, guidelines could advocate for more aggressive management of atrial fibrillation and a more consistent application of preventive measures, tailored to the unique requirements of different geographic areas.
In addition to the regional recommendations, our study highlighted several important associations between clinical findings, imaging, and risk factors. The higher prevalence of atrial fibrillation in maritime hospitals corresponded with an increased incidence of cardioembolic stroke, which is often associated with LVO on imaging. This finding suggests the need for more aggressive anticoagulation strategies in these regions. Moreover, imaging showed that patients with diabetes were more likely to present with lacunar infarcts, while hypertension was associated with a higher risk of hemorrhagic transformation, particularly in patients undergoing reperfusion therapy. These associations suggest that tailored strategies that include clinical and imaging findings, in conjunction with regional factors, are essential for improving stroke outcomes. Integrating these insights into clinical practice guidelines would promote region-specific stroke management and prevention, ultimately enhancing patients’ care.
There are several limitations to this study. First, our study was limited to southeastern China, which may not be fully representative of the entire maritime region’s effect on ischemic stroke. Additionally, this was a cross-sectional study that did not analyze the stroke incidence rate. Second, the patients treated at different hospitals might not necessarily reside in the surrounding areas, although we estimate this proportion to be low, indicating a minimal effect on our results. Third, the data sample from island hospitals was relatively small, which suggests that specific characteristics of the hospital are more prominent. Different islands might have distinct influences, but regardless of this possibility, our study suggests that island regions may greatly differ from coastal regions.
In summary, our findings indicate the importance of considering geographic variations when formulating public health policies and allocating medical resources for ischemic stroke treatment in southeastern China. The observed differences in stroke etiology, particularly the increasing trend of cardioembolic stroke from inland to coastal and island hospitals, highlight the need for region-specific strategies to address stroke risk factors. Policymakers should be mindful of these geographic factors to optimize stroke care and ensure equitable distribution of healthcare resources across different regions. This study lays the groundwork for future research aimed at understanding the environmental and socio-economic factors driving these geographic variations. Further investigation is required to develop and evaluate tailored clinical guidelines and public health interventions, especially in managing atrial fibrillation and the optimization of in-hospital stroke care processes. Additionally, assessing the effect of primary and secondary prevention strategies on stroke outcomes across different regions might provide important insight for advancing stroke care.
Footnotes
Acknowledgements
The authors thank the principal investigators, research practitioners, and patients involved in the study.
Author contributions
All authors greatly contributed y to the research and the preparation of this manuscript. XDL, XCL, DZ, and DX conceived the study and designed the experiments. YS and MH conducted the experiments and collected the data. XDL and YS performed the data analysis and interpretation. XDL and XCL drafted the manuscript, and all authors reviewed and approved the final version of the manuscript.
Data availability statement
The datasets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Declaration of conflicting interest
The authors declare that there is no conflict of interest.
Funding
This work was supported by the Medical Science and Technology Project of Zhejiang Province (2023XY086).
