Effect of ambient temperature changes on the treatment and prognosis in patients with acute stroke receiving intravenous thrombolysis

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Methods: From August 2017 to July 2020, we enrolled patients with acute stroke treated with intravenous rt-PA from the Stroke Emergency Map Registry Center of Taiyuan, Shanxi Province. We analyzed patient characteristics, the severity of neurological impairment, and functional outcomes at 90 days. Results: We included 1,914 patients (median age, 65[56–74] years), of whom 870 (45.45%) received rt-PA during the cold season. Patients treated during the warm season exhibited a shorter time from onset to door and shorter time from onset to intravenous thrombolysis start. A nonlinear relationship was observed between the daily mean temperature on the day of stroke onset and neurological function recovery in patients 7 days post-intravenous thrombolysis. When the temperature was approximately 10°C, neurological recovery was relatively good at 7 days. Analyzing the exposure–response relationship at specific lag times (0 and 7 days) revealed that, compared to that at 7 days, the cumulative lag effect at 0 days significantly influenced patients' neurological function on the 7th day. Conclusion: Lower ambient temperatures are associated with delayed intravenous thrombolysis and poorer functional outcomes in patients with ischemic stroke. Moreover, low temperatures negatively impact neurological recovery in patients, although no significant lag effect was observed. Further studies are needed to minimize treatment delays in patients with stroke caused by adverse weather conditions and to potentially improve outcomes. ambient temperature acute ischemic stroke intravenous thrombolysis recombinant tissue plasminogen activator Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Stroke imposes one of the highest burdens of disability and mortality in China (Wu et al. 2019 ), with its incidence rate increasing annually (Liu et al. 2023 ). Among adults aged > 40 years in China, ischemic stroke accounts for approximately 86.8% of all stroke cases (Tu et al. 2023 ). Reperfusion therapy is the most effective evidence-based intervention for treating acute ischemic stroke (AIS) and is recommended for patients with AIS within 4.5 hof symptom onset (COR I; LOE A) (Powers et al. 2019 ; Berge et al. 2021 ; Liu et al. 2023 ). However, intravenous recombinant tissue plasminogen activator (rt-PA) treatment does not achieve optimal therapeutic effects and prognoses in all patients with AIS. Consequently, clinicians and researchers continue to explore the clinical prognostic factors influencing the use of rt-PA. Well-established factors include onset-to-thrombolysis time, baseline National Institutes of Health Stroke Scale (NIHSS) score, and pre-stroke risk factors such as hypertension, diabetes, obesity, and atrial fibrillation. Recently, the relationship between meteorological factors and stroke incidence has garnered increasing attention. Epidemiological evidence indicates that specific geographical or climatic conditions, especially fluctuations in ambient temperature, can contribute to seasonal changes in stroke incidence and mortality (Lim et al. 2013 ). Ischemic stroke incidence has been associated with sudden temperature changes and increased diurnal temperature variations, and the mortality rate has a V-shaped relationship with temperature (Lim et al. 2013 ). Lower temperatures may exacerbate neurological dysfunction and lead to poorer prognoses in patients with an initial ischemic stroke (Luo 2019; Matsumaru et al. 2020 ). However, although many studies have investigated the relationship between ambient temperature and the incidence of AIS, data on whether patients with time-window AIS who require intravenous thrombolysis are affected by seasonal climate changes or related factors remain limited. Significant differences have been observed in how local populations adapt to meteorological conditions across different regions and climates. With climate change, the exposure–response relationship between meteorological conditions and high-impact weather-related diseases has shown more pronounced regional variations, highlighting the importance of region-specific research. Taiyuan, the capital city of Shanxi Province, is located in the central part of the province on the Loess Plateau (latitude 37°27′–38°25′ N, longitude 111°30′–113°09′ E). The city experiences long, cold, and dry winters; hot, humid, and rainy summers; rapid temperature increases in spring; sharp temperature drops in autumn; significant diurnal temperature variations, which are typical characteristics of a temperate continental climate. These climatic conditions can lead to blood pressure (BP) fluctuations and vascular spasms, thereby increasing the risk of developing cerebrovascular diseases. An epidemiological survey of 714,893 patients with stroke aged 40 years and above in Shanxi Province revealed that Taiyuan City had the highest proportion of stroke-related hospitalizations, reaching 3.61% (Sioutas et al. 2023 ). This indicates that stroke is particularly prevalent in Taiyuan compared to other regions in Shanxi Province. This study was based on the stroke emergency map of Taiyuan City and established a multicenter database of patients with AIS receiving intravenous thrombolysis. We aimed to determine whether environmental temperature affects the time delay and clinical outcomes in patients receiving intravenous thrombolysis. Additionally, using a distributed lag nonlinear model, we investigated whether daily average temperature variations affected the neurological recovery of patients with AIS undergoing intravenous thrombolysis. The findings of this study hold implications for formulating regional public health policies and stroke prevention strategies aimed at improving population health. Patients and Methods Study setting In this retrospective cohort study, data from 2,637 patients with stroke who received intravenous rt-PA between August 2017 and July 2020 were obtained from the stroke emergency map registry center of Taiyuan. Patients with missing baseline demographic data, incomplete medical records, or who died during the 3-month follow up were excluded. All enrolled patients were permanent residents of Taiyuan. After exclusion, 1,914 patients were analyzed (Fig. 1 ). The registry includes data from 19 hospitals across six districts, three counties, and one city in Taiyuan. All participating hospitals had stroke treatment capabilities, including intravenous thrombolysis, the presence of a stroke team that is24/7 on-call, and head computed tomography available 24/7.These factors contributed to our dataset’s robustness and ensured the findings were representative. This study was approved by the Institutional Review Board of the Second Hospital of Tianjin Medical University, Tianjin, China (KY2020K183), and was conducted in accordance with the Declaration of Helsinki. The requirement for patient consent was waived because of the retrospective nature of the study. Data collection We collected data on demographics (e.g., age and sex), symptom onset, transfer mode(emergency medical service [EMS] use and non-EMS transport), systolic and diastolic BP on admission, intervals(onset-to-door time, door-to-needle time),and medical history data, such as hypertension, diabetes mellitus, dyslipidemia, coronary heart disease (CHD), atrial fibrillation, and previous history of ischemic stroke. In addition, NIHSS scores at admission, 24h after intravenous thrombolysis, and discharge were documented. All included patients were hospitalized within 7days of symptom onset. The modified Rankin scale (mRS) score was used to evaluate patients’ functional outcomes at 90 days. A good outcome was defined as an mRS score of 0–2 [vs. 3–5], whereas an independent outcome was defined as an mRS score of 0–1 [vs. 2–5]. Meteorological data between August 1, 2017, and July 31, 2020, were provided by Shanxi Meteorological Bureau, including the daily mean temperature (Tm, ℃), daily maximum temperature (Tmax,℃),daily minimum temperature (Tmin,℃), daily mean relative humidity (RH, %), daily mean atmospheric pressure (hPa), and wind speed (ms − 1 ). Data analysis We examined the short-term association between environmental temperature and the prognosis of patients with AIS receiving intravenous thrombolysis during warm and cold seasons. We defined April to September as the warm season and October to March of the following year as the cold season (Yang et al. 2018 ).Continuous variables are presented as medians with medians (with first [Q1] and third [Q3] quartiles), whereas categorical variables are presented as counts and percentages. The Wilcoxon rank-sum and chi-square tests were used to compare characteristics between patients receiving rt-PA in the warm and cold seasons. We also examined temporal variations in meteorological factors monthly from August 2018 to July 2020 (Supplementary Figure S1 ). Furthermore, Pearson’s correlation analysis was used to investigate the relationships between various meteorological indicators, and a correlation heatmap was generated (Supplementary Figure S2 ). Generalized linear models were employed to assess the relationship between environmental temperature and stroke severity at 24 h, 7 days, and 3 months post-thrombolysis. These models adjusted for potential confounders, including age, dyslipidemia, CHD, admission systolic BP (SBP), arrival mode, admission NIHSS score, and onset-to-needle time. These findings are summarized in a forest plot. The distributed lag nonlinear model was employed to evaluate the impact of temperature fluctuations on stroke severity in patients following intravenous thrombolysis. The RH and wind speed were controlled using a natural cubic spline with 3 degrees of freedom. Confounding variables, including age, dyslipidemia, CHD, and admission SBP, were adjusted. Temperature variations were modeled using a cross-basis function to capture the exposure-lag-response relationship, with a lag period of 30 days selected to capture the lagged effects. Additionally, we analyzed the exposure-response relationship at specific lag times (0, 7 days). Three-dimensional graphs of stroke severity and lag-response curves at different temperatures were plotted. Two-sided p values < 0.05 were used to connote significance for all statistical tests. Data analyses were performed using R, version 4.4.1(R Foundation for Statistical Computing, Vienna, Austria). Results Clinical data and weather conditions As shown in Table 1, 1,914 patients who met the inclusion criteria between August 2017 and July 2020 were included in this study. The median age was 65[56–74] years, and 1,337 (69.85%) were men. A total of 870(45.45%) patients received rt-PA during the cold season. Compared with patients treated in the warm season, those treated in the cold season were more likely to have higher SBP levels at admission ( p <0.05). Data on the meteorological parameters for the same period in Taiyuan are summarized in Supplementary Table 1 and Supplementary Figure 2. The daily mean temperature was 12.47℃, ranging from −13.3 to 28.4℃. The Tm positively correlated with RH, Tmax, and Tmin (all P < 0.01) and was significantly negatively correlated with the daily atmospheric pressure (r = −0.82, p < 0.01). Quality control metrics of thrombolytic therapy Table 2 shows that patients who received intravenous thrombolysis in the warm season exhibited a shorter time from onset to door (median [Q1–Q3], 100 [62–140] vs.110[70–152] min) and a shorter median onset-to-needle time (median [Q1–Q3], 155[116–195] vs.165 [130–206] min). We compared patients treated with rt-PA between the two periods according to time stratification. The proportion of patients with an onset-to-door time ≤ 2 hand ≤ 3.5 h was higher in the warm season than in the cold season (66.0% vs.59.0%, p =0.002; 91.8% vs.88.5%, p =0.020). Similar results were observed for onset-to-needle time ≤ 2.5 h, ≤ 3 h, and ≤ 3.5 h, (47.7% vs.40.7%, P=0.002; 68.6% vs. 60.7%, p <0.001; 82.3% vs.77.5%, p =0.010), respectively (Table 3). Effects of different periods and cumulative lags on admission severity and clinical outcomes The adjusted estimates of each endpoint according to different periods are presented in Figure 2. After risk adjustment, patients who received rt-PA in the warm season had lower NIHSS scores at 7 days (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.30–1.24). Additionally, they had a higher likelihood of achieving a nondisabled outcome (mRS 0–1) at 90 days and a favorable clinical outcome (mRS 0–2) at 90 days(mRS score 0–1 at 90 days, aOR, 1.34; 95% CI, 1.03–1.76;mRS score 0–2 at 90 days, aOR, 1.35; 95% CI, 1.08–1.71).No significant differences were observed between the groups in the incidence of symptomatic intracerebral hemorrhage (aOR, 1.15; 95% CI, 0.75–1.77). Exposure–response relationship between temperature variations and the improvement of neurological function in patients who received intravenous thrombolysis Overall, the Tm on the day of stroke onset exhibited a non-linear relationship with the degree of neurological function recovery in patients 7 days post-intravenous thrombolysis (Figure 3). Lower temperatures were associated with a negative effect on the recovery of neurological function following intravenous thrombolysis. When the Tmwas approximately 10°C, the β of the NIHSS score reached its minimum, indicating that neurological recovery was relatively good at 7 days. However, when Tm was>25°C, the cumulative β became positive, suggesting poorer neurological recovery, although the difference was not significant (Figure 4). Further exposure–response analyses were conducted at specific lag times (0 and 7 days) (Supplementary Figures S3 and S4). The Tm on the day of onset lagged by 0 days, which significantly affected the recovery of neurological function at 7 days. Notably, when Tm was 0°C, the β coefficient was negative, indicating that higher temperatures were associated with improved neurological function. However, this lag effect was not observed at a lag time of 7 days. This suggested that low temperatures negatively impacted neurological recovery in patients undergoing thrombolysis, but there was no evident cumulative lag effect. Discussion The main finding of this observational study is that ambient temperature changes are significantly associated with stroke severity and clinical outcomes in patients with ischemic stroke undergoing intravenous thrombolysis. Compared to those treated in the cold season, patients who received rt-PA during thewarm season arrived at the hospital more quickly and had an increased likelihood of a good outcome at 90 days. Clinical practice suggests that the benefits of intravenous thrombolysis in AIS are time-dependent (Qin et al. 2017 ). Early thrombolytic treatment was associated with a higher rate of independent ambulation at discharge. The public's insufficient awareness of the warning signs of a potential stroke and the use of EMS were regarded as decisive factors for prehospital delay (Saver et al. 2013 ; Yoon et al. 2022 ). Therefore, several interventions have been implemented to address these issues, including the construction of stroke centers across hospitals, the promotion of stroke emergency maps (Gao et al. 2022 ),and the dissemination of simple mnemonics such as “FAST” which stands for “Face Arm Speech Test” (Zhang et al. 2020 ) or “stroke-1-2-0” (Robinson et al. 2013 ).Media campaigns were implemented to improve public awareness of stroke and increase the usage of EMS. Our study findings suggest that low temperatures may delay patient arrival times. Georgios et al. (Sioutas GS et al. 2023 ) studied 543 patients with AIS who underwent mechanical thrombectomy and reported findings consistent with our findings. Although the patients included in their study were transferred by EMS, daily drizzle increased the transport times for ground transportation. Therefore, it is necessary to urge the government to develop new measures to reduce pre-hospital delays caused by weather conditions, such as prehospital mobile stroke unit management (Zhao and Liu 2017 ), which has been proven to increase the rate of intravenous thrombolysis and reduce disability at hospital discharge. More patients received rt-PA and had better clinical outcomes in the warm season than in the cold season during this study, possibly because of the involvement of several mechanisms. First, the time from disease onset to receiving intravenous thrombolysis was shorter during the warm season. Second, cold ambient temperature is associated with an increase in the adenosine diphosphate-induced platelet aggregation rate (Mac Grory et al. 2024 ), which may lead to the re-formation of thrombus after thrombolysis, leading to early neurological deterioration. Third, exposure to cold may induce vasoconstriction, increase inflammation (Chen et al. 2024 ), aggravate vascular endothelial injury, and promote thrombosis, leading to a poor prognosis. Further prospective studies are needed to validate these findings. Current research on whether temperature changes on the day of symptom onset affect the improvement in neurological function after stroke is still limited. Most studies have found that extreme temperatures (either too high or too low) may increase the risk and severity of stroke admission and lead to a worse prognosis (Qi et al. 2021 ), whereas moderate temperatures may promote neurological recovery. Herein, when the Tm was approximately 10°C, patients showed relatively better neurological recovery on the 7th day. This may be because this temperature is close to the average annual temperature of Taiyuan City (12.47°C), which enhances the body's adaptability, reduces inflammatory responses, and helps maintain stable blood circulation and metabolic conditions. A 13-year study (2001–2013) in Madrid, Spain, found that environmental factors, including air pollutants and apparent temperature,have potential nonlinear and delayed effects on the prognosis of ischemic stroke, with cumulative effects lasting up to 14 days (Chu et al. 2018 ). Another study on the clinical prognosis of patients with first-time ischemic stroke during cold waves indicated that cold waves may affect neurological recovery for at least 7 days. In our study, we analyzed the exposure–response relationship at specific lag times (0 and 7 days) and found that compared to the cumulative lag effect at 7 days, 0 days significantly influenced the patients' neurological function on the 7th day. Notably, when the temperature was below 0°C, patients' neurological function on the 7th day was worse; however, no significant cumulative lag effect was observed. The mechanism underlying this result may be related to the study population of patients who underwent intravenous thrombolysis. When patients undergo reperfusion therapy with alteplase, ischemic brain tissue may experience reperfusion injury, including oxidative stress, inflammatory responses, and blood–brain barrier disruption (Royé et al. 2019 ; Li H et al. 2019 ). Temperature changes may significantly affect early pathophysiological responses of the body, and reperfusion therapy may amplify the sensitivity of the early neurological repair phase to temperature changes after intravenous thrombolysis, thereby influencing patients' neurological recovery on the day post-surgery. As the body's adaptability to the external environment increases (e.g., vascular adaptive regulation) and inpatients are influenced by other factors (such as rehabilitation training and complications), the long-term cumulative effects of temperature changes on patients are significantly reduced. Our study has some limitations. First, the patients had an inpatient stay of > 7 days. Patients who received intravenous thrombolysis in the emergency department or had a short inpatient stay were excluded from the study. This may have introduced bias into the study results. Second, patients who died were also excluded from the study. Both increases and decreases in temperature are significantly associated with ischemic stroke mortality (Chu et al. 2018 ). Future studies should expand the sample size to further explore the relationship between meteorological factors and stroke-related mortality. Third, we only analyzed the impact of Tm on patient treatment and prognosis without considering other meteorological factors. Shanxi Province is well-known a major energy and heavy industry hub in China, with high coal consumption and severe air pollution (especially particulate matter < 2.5 µm in diameter). Air pollution is a significant risk factor for cerebrovascular disease. Therefore, future research should investigate the impact of air pollution on patients with stroke. The strength of this study lies in its multicenter design, with data sourced from hospitals in Taiyuan City that are qualified to perform thrombolysis, ensuring a high level of reliability in the research results. Conclusions Lower ambient temperatures are associated with delays in intravenous thrombolysis and poorer functional outcomes in patients with stroke. Moreover, low temperatures were found to negatively impact neurological recovery in patients, although no significant lag effect was observed. Future studies should explore the biological mechanisms underlying this association. Such insights would help optimize the allocation of medical resourcesand provide scientific evidence for policymakers to promote the development of precise weather warning systems. These systems can offer timely and personalized weather forecasts and protective recommendations for populations at high risk of stroke, thereby effectively reducing treatment delays and potential adverse outcomes caused by temperature fluctuations. Declarations Acknowledgements: The authors would like to acknowledge the efforts of all the study participants and the staff of the participating hospitals. Author contributions: XL conceived and revised the manuscript. TZ collected the data and wrote and revised the manuscript. JX and XC contributed to the statistical analysis of the data. XW and XX contributed to the interpretation of the results. All authors read and approved the final manuscript. Funding: This work is supported by National Natural Science Foundation of China (42275197), the Key Projects of Tianjin Municipal Health Commission (TJWJ2023XK007), the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK 065B), and the Tianjin Center for Health and Meteorology Multidisciplinary Innovation. Conflicts of interest: The authors declare no conflicts of interest. Ethical standards: The Ethics Committee of the Second Hospital of Tianjin Medical University, Tianjin, China, approved the study protocol. Data sharing and data accessibility: The datasets used in this study are available from the corresponding author upon request. References Berge E, Whiteley W, Audebert H et al. (2021) European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 6:I–LXII. https://doi.org/10.1177/2396987321989865 Chen Z, Liu P, Xia X, Cao C, Ding Z, Li X (2024) Low ambient temperature exposure increases the risk of ischemic stroke by promoting platelet activation. Sci Total Environ 912:169235. https://doi.org/10.1016/j.scitotenv.2023.169235 Chu SY, Cox M, Fonarow GC et al. (2018) Temperature and precipitation associate with ischemic stroke outcomes in the United States. J Am Heart Assoc 7:e010020. https://doi.org/10.1161/JAHA.118.010020 Gao Z, Liu Q, Yang L, Zhu X (2022) Identification of high-risk factors for prehospital delay for patients with stroke using the risk matrix methods. Front Public Health 10:858926. https://doi.org/10.3389/fpubh.2022.858926 Li H, Yue P, Su Y, Li C (2019) Plasma levels of matrix metalloproteinase-9: A possible marker for cold-induced stroke risk in hypertensive rats. NeurosciLett 709:134399. https://doi.org/10.1016/j.neulet.2019.134399 Lim YH, Kim H, Hong YC (2013) Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature. Int J Biometeorol 57:145–153. https://doi.org/10.1007/s00484-012-0542-x Liu L, Li Z, Zhou H et al. (2023) Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: Executive summary and 2023 update. Stroke Vasc Neurol 8:e3. https://doi.org/10.1136/svn-2023-002998 Luo L, Jiang, J, Yu, C, Luo, B, & Nan, P. ( (2019) Analysis of stroke inpatients and hospitalization expenses over 40 years old in 184 hospitals in Shanxi Province. Chin J Health Stat 36:185–188 Mac Grory B, Sun JL, Alhanti B et al. (2024) Mobile stroke unit management in patients with acute ischemic stroke eligible for intravenous thrombolysis. JAMA Neurol 81:1250–1262. https://doi.org/10.1001/jamaneurol.2024.3659 Matsumaru N, Okada H, Suzuki K et al. (2020) Weather fluctuations may have an impact on stroke occurrence in a society: A population-based cohort study. Cerebrovasc Dis Extra 10:1–10. https://doi.org/10.1159/000505122 Powers WJ, Rabinstein AA, Ackerson T et al. (2019) Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 50:e344–e418. https://doi.org/10.1161/STR.0000000000000211 Qi X, Wang Z, Xia X et al. (2021) The effects of heatwaves and cold spells on patients admitted with acute ischemic stroke. Ann Transl Med 9:309. https://doi.org/10.21037/atm-20-4256 Qin L, Gu J, Liang S et al. (2017) Seasonal association between ambient ozone and mortality in Zhengzhou, China. Int J Biometeorol 61:1003–1010. https://doi.org/10.1007/s00484-016-1279-8 Robinson TG, Reid A, HauntonVJ, Wilson A, Naylor AR (2013) The face arm speech test: Does it encourage rapid recognition of important stroke warning symptoms? Emerg Med J 30:467–471. https://doi.org/10.1136/emermed-2012-201471 Royé D, Zarrabeitia MT, Riancho J, Santurtún A (2019) A time series analysis of the relationship between apparent temperature, air pollutants and ischemic stroke in Madrid, Spain. Environ Res 173:349–358. https://doi.org/10.1016/j.envres.2019.03.065 Saver JL, Fonarow GC, Smith EE et al. (2013) Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 309:2480–2488. https://doi.org/10.1001/jama.2013.6959 Sioutas GS, Amllay A, Chen CJ et al. (2023) The impact of weather and mode of transport on outcomes of patients with acute ischemic stroke undergoing mechanical thrombectomy. Neurosurgery 93:144–155. https://doi.org/10.1227/neu.0000000000002391 Tu WJ, Zhao Z, Yin P et al. (2023) Estimated burden of stroke in China in 2020. JAMA Netw Open 6:e231455. https://doi.org/10.1001/jamanetworkopen.2023.1455 Wu S, Wu B, Liu M et al. (2019) Stroke in China: Advances and challenges in epidemiology, prevention, and management. Lancet Neurol 18:394–405. https://doi.org/10.1016/S1474-4422(18)30500-3 Yang J, Zhou M, Li M et al. (2018) Vulnerability to the impact of temperature variability on mortality in 31 major Chinese cities. Environ Pollut 239:631–637. https://doi.org/10.1016/j.envpol.2018.04.090 Yoon CW, Oh H, Lee J et al. (2022) Comparisons of prehospital delay and related factors between acute ischemic stroke and acute myocardial infarction. J Am Heart Assoc 11:e023214. https://doi.org/10.1161/JAHA.121.023214 Zhang T, Zhang X, Sun H et al. (2020) Improving timely treatment with a stroke emergency map: The case of northern China. Brain Behav 10:e01743. https://doi.org/10.1002/brb3.1743 Zhao J, Liu R (2017) Stroke 1-2-0: A rapid response programme for stroke in China. Lancet Neurol 16:27–28. https://doi.org/10.1016/S1474-4422(16)30283-6 Tables Tables 1 to 3 are available in the Supplementary Files section Supplementary Files Table13.docx SupplementaryFigureS1.jpg Supplementary Fig S1 The temporal variations in meteorological factors on a monthly from August 2018 to July 2020 SupplementaryFigureS2.jpg Supplementary Fig S2 Meteorological factor correlation heatmap SupplementaryFigureS3.jpg Supplementary Fig S3 Impact of lag 0 temperature on NIHSS scores at 7 days post-thrombolysis SupplementaryFigureS4.jpg Supplementary Fig S4 Impact of lag 7 temperature on NIHSS scores at 7 days post-thrombolysis SupplementaryTable1.docx clinicaldata.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 11 May, 2025 Reviewers invited by journal 08 May, 2025 Editor assigned by journal 24 Apr, 2025 First submitted to journal 23 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Li","email":"","orcid":"https://orcid.org/0000-0002-2977-5075","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-04-22 12:15:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6504167/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6504167/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82775909,"identity":"f3e60cce-0d6c-4721-9e7f-907facd61af1","added_by":"auto","created_at":"2025-05-15 07:17:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":99805,"visible":true,"origin":"","legend":"\u003cp\u003eOverview of patients included\u003c/p\u003e","description":"","filename":"Figure1.Overviewofpatientsincluded.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/25af5c3d535b371197aed6fb.jpg"},{"id":82775908,"identity":"728f8021-0d58-467a-a318-19b2cd03f25a","added_by":"auto","created_at":"2025-05-15 07:17:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75314,"visible":true,"origin":"","legend":"\u003cp\u003eAdjusted association between_defferent periods and key study end points\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value, adjusted for Age, Hyperlipidemia, Coronary heart disease, Admission systolic BP, Arrival mode, Admission NIHSS score and onset to needle time.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/7115e6f7ea1791ad15bd4e44.jpg"},{"id":82775913,"identity":"ec7ab28c-caa8-46e2-b0c4-27e1b3f06806","added_by":"auto","created_at":"2025-05-15 07:17:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":272506,"visible":true,"origin":"","legend":"\u003cp\u003e3D plot of the relationship between mean tempepature and NIHSS score at different lag days\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/813aa8689074987692c73953.jpg"},{"id":82775267,"identity":"4bda15d7-8181-4294-a061-5f896c7e7610","added_by":"auto","created_at":"2025-05-15 07:09:56","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":37896,"visible":true,"origin":"","legend":"\u003cp\u003eNonlinear relationship between mean temperature on the day of onset and NIHSS scores at 7 days post-thrombolysis\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/1f74c12589119b2d24d760f6.jpg"},{"id":82775943,"identity":"82ea6df7-2e60-4bb4-bb70-6465334c153b","added_by":"auto","created_at":"2025-05-15 07:18:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1065150,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/386388f7-953f-43ef-ab23-dec0cda2ece3.pdf"},{"id":82775910,"identity":"100a7cca-5d1b-4815-940f-7cd0ae65bb15","added_by":"auto","created_at":"2025-05-15 07:17:56","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":27790,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Table13.docx","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/61edee9792788c46e8e5269b.docx"},{"id":82775911,"identity":"779753be-621f-4d75-b86f-cb5edbf62d04","added_by":"auto","created_at":"2025-05-15 07:17:56","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":252429,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig S1\u003c/strong\u003e The temporal variations in meteorological factors on a monthly from August 2018 to July 2020\u003c/p\u003e","description":"","filename":"SupplementaryFigureS1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/37f0e1456f60586257f7d28c.jpg"},{"id":82775272,"identity":"ce41de24-14a5-4cdf-9c36-267b599ebd48","added_by":"auto","created_at":"2025-05-15 07:09:56","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":132802,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig S2 \u003c/strong\u003eMeteorological factor correlation heatmap\u003c/p\u003e","description":"","filename":"SupplementaryFigureS2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/f2c872c3ff7abccb67298156.jpg"},{"id":82775912,"identity":"37f248f4-622f-4ad3-abfe-322ae8ce8c28","added_by":"auto","created_at":"2025-05-15 07:17:56","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":36136,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig S3 \u003c/strong\u003eImpact of lag 0 temperature on NIHSS scores at 7 days post-thrombolysis\u003c/p\u003e","description":"","filename":"SupplementaryFigureS3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/4998d6594ca84498ce3ff1c3.jpg"},{"id":82775282,"identity":"b9147ee9-c013-46b2-8439-3c5627783a08","added_by":"auto","created_at":"2025-05-15 07:09:56","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":34240,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig S4 \u003c/strong\u003eImpact of lag 7 temperature on NIHSS scores at 7 days post-thrombolysis\u003c/p\u003e","description":"","filename":"SupplementaryFigureS4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/f33a34f81d267029d3b2f107.jpg"},{"id":82775274,"identity":"ef066522-d5b8-4ea5-9d47-3c349ab9a34f","added_by":"auto","created_at":"2025-05-15 07:09:56","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":17613,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/cd2571b305f6b8c59ec552d2.docx"},{"id":82775286,"identity":"82f00f49-9aa7-4c66-9c95-792e6cbc3ca4","added_by":"auto","created_at":"2025-05-15 07:09:56","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":460198,"visible":true,"origin":"","legend":"","description":"","filename":"clinicaldata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6504167/v1/d135eea78f3452c4d59f81f5.xlsx"}],"financialInterests":"","formattedTitle":"Effect of ambient temperature changes on the treatment and prognosis in patients with acute stroke receiving intravenous thrombolysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStroke imposes one of the highest burdens of disability and mortality in China (Wu et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), with its incidence rate increasing annually (Liu et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Among adults aged\u0026thinsp;\u0026gt;\u0026thinsp;40 years in China, ischemic stroke accounts for approximately 86.8% of all stroke cases (Tu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Reperfusion therapy is the most effective evidence-based intervention for treating acute ischemic stroke (AIS) and is recommended for patients with AIS within 4.5 hof symptom onset (COR I; LOE A) (Powers et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Berge et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Liu et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). However, intravenous recombinant tissue plasminogen activator (rt-PA) treatment does not achieve optimal therapeutic effects and prognoses in all patients with AIS. Consequently, clinicians and researchers continue to explore the clinical prognostic factors influencing the use of rt-PA.\u003c/p\u003e \u003cp\u003eWell-established factors include onset-to-thrombolysis time, baseline National Institutes of Health Stroke Scale (NIHSS) score, and pre-stroke risk factors such as hypertension, diabetes, obesity, and atrial fibrillation. Recently, the relationship between meteorological factors and stroke incidence has garnered increasing attention. Epidemiological evidence indicates that specific geographical or climatic conditions, especially fluctuations in ambient temperature, can contribute to seasonal changes in stroke incidence and mortality (Lim et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Ischemic stroke incidence has been associated with sudden temperature changes and increased diurnal temperature variations, and the mortality rate has a V-shaped relationship with temperature (Lim et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Lower temperatures may exacerbate neurological dysfunction and lead to poorer prognoses in patients with an initial ischemic stroke (Luo 2019; Matsumaru et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). However, although many studies have investigated the relationship between ambient temperature and the incidence of AIS, data on whether patients with time-window AIS who require intravenous thrombolysis are affected by seasonal climate changes or related factors remain limited.\u003c/p\u003e \u003cp\u003eSignificant differences have been observed in how local populations adapt to meteorological conditions across different regions and climates. With climate change, the exposure\u0026ndash;response relationship between meteorological conditions and high-impact weather-related diseases has shown more pronounced regional variations, highlighting the importance of region-specific research. Taiyuan, the capital city of Shanxi Province, is located in the central part of the province on the Loess Plateau (latitude 37\u0026deg;27\u0026prime;\u0026ndash;38\u0026deg;25\u0026prime; N, longitude 111\u0026deg;30\u0026prime;\u0026ndash;113\u0026deg;09\u0026prime; E). The city experiences long, cold, and dry winters; hot, humid, and rainy summers; rapid temperature increases in spring; sharp temperature drops in autumn; significant diurnal temperature variations, which are typical characteristics of a temperate continental climate. These climatic conditions can lead to blood pressure (BP) fluctuations and vascular spasms, thereby increasing the risk of developing cerebrovascular diseases. An epidemiological survey of 714,893 patients with stroke aged 40 years and above in Shanxi Province revealed that Taiyuan City had the highest proportion of stroke-related hospitalizations, reaching 3.61% (Sioutas et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). This indicates that stroke is particularly prevalent in Taiyuan compared to other regions in Shanxi Province.\u003c/p\u003e \u003cp\u003eThis study was based on the stroke emergency map of Taiyuan City and established a multicenter database of patients with AIS receiving intravenous thrombolysis. We aimed to determine whether environmental temperature affects the time delay and clinical outcomes in patients receiving intravenous thrombolysis. Additionally, using a distributed lag nonlinear model, we investigated whether daily average temperature variations affected the neurological recovery of patients with AIS undergoing intravenous thrombolysis. The findings of this study hold implications for formulating regional public health policies and stroke prevention strategies aimed at improving population health.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eIn this retrospective cohort study, data from 2,637 patients with stroke who received intravenous rt-PA between August 2017 and July 2020 were obtained from the stroke emergency map registry center of Taiyuan. Patients with missing baseline demographic data, incomplete medical records, or who died during the 3-month follow up were excluded. All enrolled patients were permanent residents of Taiyuan. After exclusion, 1,914 patients were analyzed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe registry includes data from 19 hospitals across six districts, three counties, and one city in Taiyuan. All participating hospitals had stroke treatment capabilities, including intravenous thrombolysis, the presence of a stroke team that is24/7 on-call, and head computed tomography available 24/7.These factors contributed to our dataset\u0026rsquo;s robustness and ensured the findings were representative.\u003c/p\u003e \u003cp\u003e This study was approved by the Institutional Review Board of the Second Hospital of Tianjin Medical University, Tianjin, China (KY2020K183), and was conducted in accordance with the Declaration of Helsinki. The requirement for patient consent was waived because of the retrospective nature of the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eWe collected data on demographics (e.g., age and sex), symptom onset, transfer mode(emergency medical service [EMS] use and non-EMS transport), systolic and diastolic BP on admission, intervals(onset-to-door time, door-to-needle time),and medical history data, such as hypertension, diabetes mellitus, dyslipidemia, coronary heart disease (CHD), atrial fibrillation, and previous history of ischemic stroke. In addition, NIHSS scores at admission, 24h after intravenous thrombolysis, and discharge were documented. All included patients were hospitalized within 7days of symptom onset.\u003c/p\u003e \u003cp\u003eThe modified Rankin scale (mRS) score was used to evaluate patients\u0026rsquo; functional outcomes at 90 days. A good outcome was defined as an mRS score of 0\u0026ndash;2 [vs. 3\u0026ndash;5], whereas an independent outcome was defined as an mRS score of 0\u0026ndash;1 [vs. 2\u0026ndash;5].\u003c/p\u003e \u003cp\u003eMeteorological data between August 1, 2017, and July 31, 2020, were provided by Shanxi Meteorological Bureau, including the daily mean temperature (Tm, ℃), daily maximum temperature (Tmax,℃),daily minimum temperature (Tmin,℃), daily mean relative humidity (RH, %), daily mean atmospheric pressure (hPa), and wind speed (ms\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eWe examined the short-term association between environmental temperature and the prognosis of patients with AIS receiving intravenous thrombolysis during warm and cold seasons. We defined April to September as the warm season and October to March of the following year as the cold season (Yang et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).Continuous variables are presented as medians with medians (with first [Q1] and third [Q3] quartiles), whereas categorical variables are presented as counts and percentages. The Wilcoxon rank-sum and chi-square tests were used to compare characteristics between patients receiving rt-PA in the warm and cold seasons. We also examined temporal variations in meteorological factors monthly from August 2018 to July 2020 (Supplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Furthermore, Pearson\u0026rsquo;s correlation analysis was used to investigate the relationships between various meteorological indicators, and a correlation heatmap was generated (Supplementary Figure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGeneralized linear models were employed to assess the relationship between environmental temperature and stroke severity at 24 h, 7 days, and 3 months post-thrombolysis. These models adjusted for potential confounders, including age, dyslipidemia, CHD, admission systolic BP (SBP), arrival mode, admission NIHSS score, and onset-to-needle time. These findings are summarized in a forest plot.\u003c/p\u003e \u003cp\u003eThe distributed lag nonlinear model was employed to evaluate the impact of temperature fluctuations on stroke severity in patients following intravenous thrombolysis. The RH and wind speed were controlled using a natural cubic spline with 3 degrees of freedom. Confounding variables, including age, dyslipidemia, CHD, and admission SBP, were adjusted. Temperature variations were modeled using a cross-basis function to capture the exposure-lag-response relationship, with a lag period of 30 days selected to capture the lagged effects. Additionally, we analyzed the exposure-response relationship at specific lag times (0, 7 days). Three-dimensional graphs of stroke severity and lag-response curves at different temperatures were plotted. Two-sided \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were used to connote significance for all statistical tests. Data analyses were performed using R, version 4.4.1(R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical data and weather conditions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, 1,914 patients who met the inclusion criteria between August 2017 and July 2020 were included in this study. The median age was 65[56\u0026ndash;74] years, and 1,337 (69.85%) were men. A total of 870(45.45%) patients received rt-PA during the cold season. Compared with patients treated in the warm season, those treated in the cold season were more likely to have higher SBP levels at admission (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eData on the meteorological parameters for the same period in Taiyuan are summarized in Supplementary Table 1 and Supplementary Figure 2. The daily mean temperature was 12.47℃, ranging from \u0026minus;13.3 to 28.4℃. The Tm positively correlated with RH, Tmax, and Tmin (all P \u0026lt; 0.01) and was significantly negatively correlated with the daily atmospheric pressure (r = \u0026minus;0.82, \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.01).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality control metrics of thrombolytic therapy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows that patients who received intravenous thrombolysis in the warm season exhibited a shorter time from onset to door (median [Q1\u0026ndash;Q3], 100 [62\u0026ndash;140] vs.110[70\u0026ndash;152] min) and a shorter median onset-to-needle time (median [Q1\u0026ndash;Q3], 155[116\u0026ndash;195] vs.165 [130\u0026ndash;206] min).\u003c/p\u003e\n\u003cp\u003eWe compared patients treated with rt-PA between the two periods according to time stratification. The proportion of patients with an onset-to-door time \u0026le; 2 hand \u0026le; 3.5 h was higher in the warm season than in the cold season (66.0% vs.59.0%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e=0.002; 91.8% vs.88.5%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e=0.020). Similar results were observed for onset-to-needle time \u0026le; 2.5 h, \u0026le; 3 h, and \u0026le; 3.5 h, (47.7% vs.40.7%, P=0.002; 68.6% vs. 60.7%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt;0.001; 82.3% vs.77.5%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e=0.010), respectively (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of different periods and cumulative lags on admission severity and clinical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe adjusted estimates of each endpoint according to different periods are presented in Figure 2. After risk adjustment, patients who received rt-PA in the warm season had lower NIHSS scores at 7 days (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.30\u0026ndash;1.24). Additionally, they had a higher likelihood of achieving a nondisabled outcome (mRS 0\u0026ndash;1) at 90 days and a favorable clinical outcome (mRS 0\u0026ndash;2) at 90 days(mRS score 0\u0026ndash;1 at 90 days, aOR, 1.34; 95% CI, 1.03\u0026ndash;1.76;mRS score 0\u0026ndash;2 at 90 days, aOR, 1.35; 95% CI, 1.08\u0026ndash;1.71).No significant differences were observed between the groups in the incidence of symptomatic intracerebral hemorrhage (aOR, 1.15; 95% CI, 0.75\u0026ndash;1.77).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure\u0026ndash;response relationship between temperature variations and the improvement of neurological function in patients who received intravenous thrombolysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, the Tm on the day of stroke onset exhibited a non-linear relationship with the degree of neurological function recovery in patients 7 days post-intravenous thrombolysis (Figure 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLower temperatures were associated with a negative effect on the recovery of neurological function following intravenous thrombolysis. When the Tmwas approximately 10\u0026deg;C, the \u0026beta; of the NIHSS score reached its minimum, indicating that neurological recovery was relatively good at 7 days. However, when Tm was\u0026gt;25\u0026deg;C, the cumulative \u0026beta; became positive, suggesting poorer neurological recovery, although the difference was not significant (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurther exposure\u0026ndash;response analyses were conducted at specific lag times (0 and 7 days) (Supplementary Figures S3 and S4). The Tm on the day of onset lagged by 0 days, which significantly affected the recovery of neurological function at 7 days. Notably, when Tm was \u0026lt;0\u0026deg;C, the \u0026beta; coefficient was positive, whereas when Tm was \u0026gt;0\u0026deg;C, the \u0026beta; coefficient was negative, indicating that higher temperatures were associated with improved neurological function. However, this lag effect was not observed at a lag time of 7 days. This suggested that low temperatures negatively impacted neurological recovery in patients undergoing thrombolysis, but there was no evident cumulative lag effect.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main finding of this observational study is that ambient temperature changes are significantly associated with stroke severity and clinical outcomes in patients with ischemic stroke undergoing intravenous thrombolysis. Compared to those treated in the cold season, patients who received rt-PA during thewarm season arrived at the hospital more quickly and had an increased likelihood of a good outcome at 90 days.\u003c/p\u003e \u003cp\u003eClinical practice suggests that the benefits of intravenous thrombolysis in AIS are time-dependent (Qin et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Early thrombolytic treatment was associated with a higher rate of independent ambulation at discharge. The public's insufficient awareness of the warning signs of a potential stroke and the use of EMS were regarded as decisive factors for prehospital delay (Saver et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Yoon et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, several interventions have been implemented to address these issues, including the construction of stroke centers across hospitals, the promotion of stroke emergency maps (Gao et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2022\u003c/span\u003e),and the dissemination of simple mnemonics such as \u0026ldquo;FAST\u0026rdquo; which stands for \u0026ldquo;Face Arm Speech Test\u0026rdquo; (Zhang et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) or \u0026ldquo;stroke-1-2-0\u0026rdquo; (Robinson et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2013\u003c/span\u003e).Media campaigns were implemented to improve public awareness of stroke and increase the usage of EMS. Our study findings suggest that low temperatures may delay patient arrival times. Georgios et al. (Sioutas GS et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) studied 543 patients with AIS who underwent mechanical thrombectomy and reported findings consistent with our findings. Although the patients included in their study were transferred by EMS, daily drizzle increased the transport times for ground transportation. Therefore, it is necessary to urge the government to develop new measures to reduce pre-hospital delays caused by weather conditions, such as prehospital mobile stroke unit management (Zhao and Liu \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), which has been proven to increase the rate of intravenous thrombolysis and reduce disability at hospital discharge.\u003c/p\u003e \u003cp\u003eMore patients received rt-PA and had better clinical outcomes in the warm season than in the cold season during this study, possibly because of the involvement of several mechanisms. First, the time from disease onset to receiving intravenous thrombolysis was shorter during the warm season. Second, cold ambient temperature is associated with an increase in the adenosine diphosphate-induced platelet aggregation rate (Mac Grory et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), which may lead to the re-formation of thrombus after thrombolysis, leading to early neurological deterioration. Third, exposure to cold may induce vasoconstriction, increase inflammation (Chen et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), aggravate vascular endothelial injury, and promote thrombosis, leading to a poor prognosis. Further prospective studies are needed to validate these findings.\u003c/p\u003e \u003cp\u003eCurrent research on whether temperature changes on the day of symptom onset affect the improvement in neurological function after stroke is still limited. Most studies have found that extreme temperatures (either too high or too low) may increase the risk and severity of stroke admission and lead to a worse prognosis (Qi et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), whereas moderate temperatures may promote neurological recovery.\u003c/p\u003e \u003cp\u003eHerein, when the Tm was approximately 10\u0026deg;C, patients showed relatively better neurological recovery on the 7th day. This may be because this temperature is close to the average annual temperature of Taiyuan City (12.47\u0026deg;C), which enhances the body's adaptability, reduces inflammatory responses, and helps maintain stable blood circulation and metabolic conditions. A 13-year study (2001\u0026ndash;2013) in Madrid, Spain, found that environmental factors, including air pollutants and apparent temperature,have potential nonlinear and delayed effects on the prognosis of ischemic stroke, with cumulative effects lasting up to 14 days (Chu et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Another study on the clinical prognosis of patients with first-time ischemic stroke during cold waves indicated that cold waves may affect neurological recovery for at least 7 days. In our study, we analyzed the exposure\u0026ndash;response relationship at specific lag times (0 and 7 days) and found that compared to the cumulative lag effect at 7 days, 0 days significantly influenced the patients' neurological function on the 7th day. Notably, when the temperature was below 0\u0026deg;C, patients' neurological function on the 7th day was worse; however, no significant cumulative lag effect was observed.\u003c/p\u003e \u003cp\u003eThe mechanism underlying this result may be related to the study population of patients who underwent intravenous thrombolysis. When patients undergo reperfusion therapy with alteplase, ischemic brain tissue may experience reperfusion injury, including oxidative stress, inflammatory responses, and blood\u0026ndash;brain barrier disruption (Roy\u0026eacute; et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Li H et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Temperature changes may significantly affect early pathophysiological responses of the body, and reperfusion therapy may amplify the sensitivity of the early neurological repair phase to temperature changes after intravenous thrombolysis, thereby influencing patients' neurological recovery on the day post-surgery. As the body's adaptability to the external environment increases (e.g., vascular adaptive regulation) and inpatients are influenced by other factors (such as rehabilitation training and complications), the long-term cumulative effects of temperature changes on patients are significantly reduced.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, the patients had an inpatient stay of \u0026gt;\u0026thinsp;7 days. Patients who received intravenous thrombolysis in the emergency department or had a short inpatient stay were excluded from the study. This may have introduced bias into the study results. Second, patients who died were also excluded from the study. Both increases and decreases in temperature are significantly associated with ischemic stroke mortality (Chu et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Future studies should expand the sample size to further explore the relationship between meteorological factors and stroke-related mortality. Third, we only analyzed the impact of Tm on patient treatment and prognosis without considering other meteorological factors. Shanxi Province is well-known a major energy and heavy industry hub in China, with high coal consumption and severe air pollution (especially particulate matter\u0026thinsp;\u0026lt;\u0026thinsp;2.5 \u0026micro;m in diameter). Air pollution is a significant risk factor for cerebrovascular disease. Therefore, future research should investigate the impact of air pollution on patients with stroke. The strength of this study lies in its multicenter design, with data sourced from hospitals in Taiyuan City that are qualified to perform thrombolysis, ensuring a high level of reliability in the research results.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eLower ambient temperatures are associated with delays in intravenous thrombolysis and poorer functional outcomes in patients with stroke. Moreover, low temperatures were found to negatively impact neurological recovery in patients, although no significant lag effect was observed. Future studies should explore the biological mechanisms underlying this association. Such insights would help optimize the allocation of medical resourcesand provide scientific evidence for policymakers to promote the development of precise weather warning systems. These systems can offer timely and personalized weather forecasts and protective recommendations for populations at high risk of stroke, thereby effectively reducing treatment delays and potential adverse outcomes caused by temperature fluctuations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors would like to acknowledge the efforts of all the study participants and the staff of the participating hospitals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eXL conceived and revised the manuscript. TZ collected the data and wrote and revised the manuscript. JX and XC contributed to the statistical analysis of the data. XW and XX contributed to the interpretation of the results. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work is supported by National Natural Science Foundation of China (42275197), the Key Projects of Tianjin Municipal Health Commission (TJWJ2023XK007), the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK 065B), and the Tianjin Center for Health and Meteorology Multidisciplinary Innovation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical standards:\u003c/strong\u003e The Ethics Committee of the Second Hospital of Tianjin Medical University, Tianjin, China, approved the study protocol.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing and data accessibility:\u0026nbsp;\u003c/strong\u003eThe datasets used in this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBerge E, Whiteley W, Audebert H et al. (2021) European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 6:I\u0026ndash;LXII. https://doi.org/10.1177/2396987321989865\u003c/li\u003e\n \u003cli\u003eChen Z, Liu P, Xia X, Cao C, Ding Z, Li X (2024) Low ambient temperature exposure increases the risk of ischemic stroke by promoting platelet activation. Sci Total Environ 912:169235. https://doi.org/10.1016/j.scitotenv.2023.169235\u003c/li\u003e\n \u003cli\u003eChu SY, Cox M, Fonarow GC et al. (2018) Temperature and precipitation associate with ischemic stroke outcomes in the United States. J Am Heart Assoc 7:e010020. https://doi.org/10.1161/JAHA.118.010020\u003c/li\u003e\n \u003cli\u003eGao Z, Liu Q, Yang L, Zhu X (2022) Identification of high-risk factors for prehospital delay for patients with stroke using the risk matrix methods. Front Public Health 10:858926. https://doi.org/10.3389/fpubh.2022.858926\u003c/li\u003e\n \u003cli\u003eLi H, Yue P, Su Y, Li C (2019) Plasma levels of matrix metalloproteinase-9: A possible marker for cold-induced stroke risk in hypertensive rats. NeurosciLett 709:134399. https://doi.org/10.1016/j.neulet.2019.134399\u003c/li\u003e\n \u003cli\u003eLim YH, Kim H, Hong YC (2013) Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature. Int J Biometeorol 57:145\u0026ndash;153. https://doi.org/10.1007/s00484-012-0542-x\u003c/li\u003e\n \u003cli\u003eLiu L, Li Z, Zhou H et al. (2023) Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: Executive summary and 2023 update. Stroke Vasc Neurol 8:e3. https://doi.org/10.1136/svn-2023-002998\u003c/li\u003e\n \u003cli\u003eLuo L, Jiang, J, Yu, C, Luo, B, \u0026amp; Nan, P. ( (2019) Analysis of stroke inpatients and hospitalization expenses over 40 years old in 184 hospitals in Shanxi Province. Chin J Health Stat 36:185\u0026ndash;188\u003c/li\u003e\n \u003cli\u003eMac Grory B, Sun JL, Alhanti B et al. (2024) Mobile stroke unit management in patients with acute ischemic stroke eligible for intravenous thrombolysis. JAMA Neurol 81:1250\u0026ndash;1262. https://doi.org/10.1001/jamaneurol.2024.3659\u003c/li\u003e\n \u003cli\u003eMatsumaru N, Okada H, Suzuki K et al. (2020) Weather fluctuations may have an impact on stroke occurrence in a society: A population-based cohort study. Cerebrovasc Dis Extra 10:1\u0026ndash;10. https://doi.org/10.1159/000505122\u003c/li\u003e\n \u003cli\u003ePowers WJ, Rabinstein AA, Ackerson T et al. (2019) Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 50:e344\u0026ndash;e418. https://doi.org/10.1161/STR.0000000000000211\u003c/li\u003e\n \u003cli\u003eQi X, Wang Z, Xia X et al. (2021) The effects of heatwaves and cold spells on patients admitted with acute ischemic stroke. Ann Transl Med 9:309. https://doi.org/10.21037/atm-20-4256\u003c/li\u003e\n \u003cli\u003eQin L, Gu J, Liang S et al. (2017) Seasonal association between ambient ozone and mortality in Zhengzhou, China. Int J Biometeorol 61:1003\u0026ndash;1010. https://doi.org/10.1007/s00484-016-1279-8\u003c/li\u003e\n \u003cli\u003eRobinson TG, Reid A, HauntonVJ, Wilson A, Naylor AR (2013) The face arm speech test: Does it encourage rapid recognition of important stroke warning symptoms? Emerg Med J 30:467\u0026ndash;471. https://doi.org/10.1136/emermed-2012-201471\u003c/li\u003e\n \u003cli\u003eRoy\u0026eacute; D, Zarrabeitia MT, Riancho J, Santurt\u0026uacute;n A (2019) A time series analysis of the relationship between apparent temperature, air pollutants and ischemic stroke in Madrid, Spain. Environ Res 173:349\u0026ndash;358. https://doi.org/10.1016/j.envres.2019.03.065\u003c/li\u003e\n \u003cli\u003eSaver JL, Fonarow GC, Smith EE et al. (2013) Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 309:2480\u0026ndash;2488. https://doi.org/10.1001/jama.2013.6959\u003c/li\u003e\n \u003cli\u003eSioutas GS, Amllay A, Chen CJ et al. (2023) The impact of weather and mode of transport on outcomes of patients with acute ischemic stroke undergoing mechanical thrombectomy. Neurosurgery 93:144\u0026ndash;155. https://doi.org/10.1227/neu.0000000000002391\u003c/li\u003e\n \u003cli\u003eTu WJ, Zhao Z, Yin P et al. (2023) Estimated burden of stroke in China in 2020. JAMA Netw Open 6:e231455. https://doi.org/10.1001/jamanetworkopen.2023.1455\u003c/li\u003e\n \u003cli\u003eWu S, Wu B, Liu M et al. (2019) Stroke in China: Advances and challenges in epidemiology, prevention, and management. Lancet Neurol 18:394\u0026ndash;405. https://doi.org/10.1016/S1474-4422(18)30500-3\u003c/li\u003e\n \u003cli\u003eYang J, Zhou M, Li M et al. (2018) Vulnerability to the impact of temperature variability on mortality in 31 major Chinese cities. Environ Pollut 239:631\u0026ndash;637. https://doi.org/10.1016/j.envpol.2018.04.090\u003c/li\u003e\n \u003cli\u003eYoon CW, Oh H, Lee J et al. (2022) Comparisons of prehospital delay and related factors between acute ischemic stroke and acute myocardial infarction. J Am Heart Assoc 11:e023214. https://doi.org/10.1161/JAHA.121.023214\u003c/li\u003e\n \u003cli\u003eZhang T, Zhang X, Sun H et al. (2020) Improving timely treatment with a stroke emergency map: The case of northern China. Brain Behav 10:e01743. https://doi.org/10.1002/brb3.1743\u003c/li\u003e\n \u003cli\u003eZhao J, Liu R (2017) Stroke 1-2-0: A rapid response programme for stroke in China. Lancet Neurol 16:27\u0026ndash;28. https://doi.org/10.1016/S1474-4422(16)30283-6\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-biometeorology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijbm","sideBox":"Learn more about [International Journal of Biometeorology](http://link.springer.com/journal/484)","snPcode":"484","submissionUrl":"https://www.editorialmanager.com/ijbm/default2.aspx","title":"International Journal of Biometeorology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"ambient temperature, acute ischemic stroke, intravenous thrombolysis, recombinant tissue plasminogen activator","lastPublishedDoi":"10.21203/rs.3.rs-6504167/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6504167/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo determine whether environmental temperature affects the time delay and clinical outcomes in patients with acute ischemic stroke receiving intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eFrom August 2017 to July 2020, we enrolled patients with acute stroke treated with intravenous rt-PA from the Stroke Emergency Map Registry Center of Taiyuan, Shanxi Province. We analyzed patient characteristics, the severity of neurological impairment, and functional outcomes at 90 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eWe included 1,914 patients (median age, 65[56–74] years), of whom 870 (45.45%) received rt-PA during the cold season. Patients treated during the warm season exhibited a shorter time from onset to door and shorter time from onset to intravenous thrombolysis start. A nonlinear relationship was observed between the daily mean temperature on the day of stroke onset and neurological function recovery in patients 7 days post-intravenous thrombolysis. When the temperature was approximately 10°C, neurological recovery was relatively good at 7 days. Analyzing the exposure–response relationship at specific lag times (0 and 7 days) revealed that, compared to that at 7 days, the cumulative lag effect at 0 days significantly influenced patients' neurological function on the 7th day.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eLower ambient temperatures are associated with delayed intravenous thrombolysis and poorer functional outcomes in patients with ischemic stroke. Moreover, low temperatures negatively impact neurological recovery in patients, although no significant lag effect was observed. Further studies are needed to minimize treatment delays in patients with stroke caused by adverse weather conditions and to potentially improve outcomes.\u003c/p\u003e","manuscriptTitle":"Effect of ambient temperature changes on the treatment and prognosis in patients with acute stroke receiving intravenous thrombolysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 07:09:51","doi":"10.21203/rs.3.rs-6504167/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-05-11T04:31:37+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-08T09:46:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-24T07:52:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Biometeorology","date":"2025-04-23T21:12:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-biometeorology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijbm","sideBox":"Learn more about [International Journal of Biometeorology](http://link.springer.com/journal/484)","snPcode":"484","submissionUrl":"https://www.editorialmanager.com/ijbm/default2.aspx","title":"International Journal of Biometeorology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6943e9c2-08c1-429f-bd29-6a9536196f3a","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T19:04:54+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-15 07:09:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6504167","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6504167","identity":"rs-6504167","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}