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Background: Stroke represents a prominent global health issue, exhibiting the third highest incidence of disability and a significant burden on both healthcare and the economy. Stress hyperglycemia, an acute reaction of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to adverse outcomes and mortality. Several previous studies have indicated that stress hyperglycemia, as evaluated by the stress hyperglycemia ratio (SHR), significantly increases the risk of adverse outcomes and mortality in stroke patients. However, there is a lack of further investigation into the influence of dynamic changes in stress hyperglycemia on the clinical outcomes of acute ischemic stroke (AIS) patients. Consequently, we performed a meticulous analysis, considering dose-response relationships from existing studies, to ascertain the correlation between dynamic changes in stress hyperglycemia and the susceptibility to adverse outcomes in patients with AIS., Methods: This investigation was prospectively registered in PROSPERO and adhered to the PRISMA guidelines. A comprehensive search was performed across English and Chinese databases. A two-sided random-effects model was employed to consolidate the odds ratios (ORs) of the highest vs. lowest categories of SHR. Restricted cubic spline (RCS) models were employed to estimate potential non-linear trends between SHR and the risk of adverse outcomes in AIS patients. Egger's test was utilized to assess publication bias. Heterogeneity was evaluated using Cochran's Q -test. The Newcastle-Ottawa Scale (NOS) tool was employed to evaluate the risk of bias of the included studies., Results: The final analysis incorporated a total of thirteen studies, which were published between 2019 and 2023, encompassing a participant cohort of 184,179 individuals. The SHR exhibited a significant association with the risk of various adverse outcomes. Specifically, a higher SHR was correlated with a 2.64-fold increased risk of 3-month poor functional outcomes (OR: 2.64, 95% CI 2.05-3.41, I 2 = 52.3%, P < 0.001), a 3.11-fold increased risk of 3-month mortality (OR: 3.11, 95% CI 2.10-4.59, I 2 = 38.6%, P < 0.001), a 2.80-fold increased risk of 1-year mortality (OR: 2.80, 95% CI 1.81-4.31, I 2 = 88%, P < 0.001), a 3.90-fold increased risk of intracerebral hemorrhage (ICH) and 4.57-fold increased risk of symptomatic ICH (sICH) (ICH-OR: 3.90, 95% CI 1.52-10.02, I 2 = 84.3%, P = 0.005; sICH-OR: 4.57, 95% CI 2.05-10.10, I 2 = 47.3%, P < 0.001), a 1.73-fold increased risk of neurological deficits (OR: 1.73, 95 CI 1.44-2.08, I 2 = 0%, P < 0.001), and a 2.84-fold increased risk of stroke recurrence (OR: 2.84, 95 CI 1.48-5.45, I 2 = 50.3%, P = 0.002). It is noteworthy that, except for hemorrhagic transformation (HT) and stroke recurrence, the remaining adverse outcomes exhibited a "J-shaped" non-linear dose-response relationship., Conclusion: In summary, our findings collectively suggest that increased exposure to elevated SHR is robustly linked to a heightened risk of adverse outcomes and mortality in individuals with AIS, exhibiting a non-linear dose-response relationship. These results underscore the significance of SHR as a predictive factor for stroke prognosis. Therefore, further investigations are warranted to explore the role of SHR in relation to adverse outcomes in stroke patients from diverse ethnic populations. Furthermore, there is a need to explore the potential benefits of stress hyperglycemia control in alleviating the physical health burdens associated with AIS. Maintaining a lower SHR level may potentially reduce the risk of adverse stroke outcomes., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023424852., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Li and Yin.)

Objective: Stress hyperglycemia (SH) is common in patients with acute diseases, such as stroke and myocardial infarction. Stress hyperglycemia ratio (SHR) is calculated by glucose/glycated hemoglobin and has been widely used for evaluating SH. But whether SHR is associated with clinical outcomes in stroke patients remains unclear so far. Although many studies have shown that higher SHR means poor outcomes, there is still no absolute evidence that SHR plays a critical role in stroke patients. Hence, we performed a systematic review and meta-analysis aiming to investigate the association between SHR and clinical outcomes in stroke patients., Methods: We performed a comprehensive literature search of the PubMed, Embase, Cochrane Library databases, Clinicaltrials.gov, and WHO-ICTRP. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we performed our study. The Newcastle-Ottawa Scale (NOS) tool was used to examine the potential bias of included studies. The endpoints including poor outcome, mortality, neurological deficit, hemorrhagic transformation (HT), and infectious complications were statistically analyzed., Results: Sixteen retrospective studies met the eligibility criteria, and a number of 183,588 patients were included. Our meta-analysis demonstrated a significant increase in the incidence of poor outcome, according to assessment by the modified Rankin Scale (mRS) ≥ 3 points [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.99-3.22, P < 0.00001, I 2 = 68%], mortality (OR 1.96, 95% CI 1.58-2.44, P < 0.00001, I 2 = 61%), neurological deficit (OR 1.99, 95% CI 1.47-2.70, P < 0.00001, I 2 = 75%), hemorrhagic transformation (HT) (OR 3.70, 95% CI 2.69-5.08, P < 0.00001, I 2 = 0%), and infectious complications [(Pneumonia) OR 2.06, 95% CI 1.57-2.72, P < 0.00001, I 2 = 24%; (Urinary tract infection) OR 2.53, 95% CI 1.45-4.42, P = 0.001, I 2 = 57%] in stroke patients with higher SHR. However, no significant influence was observed for recanalization rate (OR 0.86, 95% CI 0.54-1.38, P = 0.53, I 2 = 0%)., Conclusion: With or without diabetes, no matter whether undergoing intravenous thrombolysis or mechanical thrombectomy, higher SHR significantly increased the occurrence of poor outcomes, mortality, neurological deficit, HT, and infectious complications. The recanalization rate was not statistically significant between the two groups. More attention must be paid in clinical practice to SH. Future investigation should focus on the diagnostic value of SHR and the early control of hyperglycemia. Meanwhile, whether SHR could become a novel and promising target for early intervention is worthy of attention in further research. Besides, the influence of the dynamic change of glucose-to-HbA1c ratio, namely SHR, on intracerebral hemorrhage outcomes requires further investigation in future research. Although no randomized double-blind studies have been conducted, the available massive sample studies reflect the actual situation in the clinic and assist clinical decision makers., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022345587., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Yin and Li.)