Stress hyperglycemia and risk of adverse outcomes in patients with acute ischemic stroke: a systematic review and dose–response meta–analysis of cohort studies
Authors: Huang Yong-Wei , Li Zong-Ping , Yin Xiao-Shuang 
Published: November 2023

BackgroundStroke 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.MethodsThis 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'sQ-test. The Newcastle-Ottawa Scale (NOS) tool was employed to evaluate the risk of bias of the included studies.ResultsThe 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,I2= 52.3%,P&lt; 0.001), a 3.11-fold increased risk of 3-month mortality (OR: 3.11, 95% CI 2.10–4.59,I2= 38.6%,P&lt; 0.001), a 2.80-fold increased risk of 1-year mortality (OR: 2.80, 95% CI 1.81–4.31,I2= 88%,P&lt; 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,I2= 84.3%,P= 0.005; sICH-OR: 4.57, 95% CI 2.05–10.10,I2= 47.3%,P&lt; 0.001), a 1.73-fold increased risk of neurological deficits (OR: 1.73, 95 CI 1.44–2.08,I2= 0%,P&lt; 0.001), and a 2.84-fold increased risk of stroke recurrence (OR: 2.84, 95 CI 1.48–5.45,I2= 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.ConclusionIn 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 registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023424852.