To the best of our knowledge, this study is the first to investigate the association between the SHR and outcomes in patients with CS. Our findings indicate that an elevated SHR (≥ 1.395) is independently associated with higher 30-day and 360-day all-cause mortality. This study underscores the prognostic significance of SHR in patients with CS.

Disruption of glucose metabolism is common in critically ill patients and has been shown to be associated with clinical outcomes [12,13,14]. Stress hyperglycemia typically refers to transient hyperglycemia that occurs during periods of stress. A combination of factors acts collectively and synergistically to induce this condition. Stress hyperglycemia is primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the sympatho-adrenal system, which release cortisol and catecholamines. These hormones further elevate blood glucose levels by promoting gluconeogenesis and glycogenolysis while inhibiting glucose uptake in peripheral tissues [3, 9]. Additionally, inflammatory mediators and altered adipokine release from adipose tissue contribute to peripheral insulin resistance and exacerbate stress hyperglycemia [9, 15]. While stress hyperglycemia has protective effects, helping maintain metabolic homeostasis and survival during stress [3], increasing evidence suggests that prolonged or inappropriate hyperglycemia is strongly associated with poor outcomes in various diseases, particularly in cardiovascular conditions. In patients with MI, elevated SHR has been significantly linked to a higher risk of all-cause mortality [16]. A meta-analysis further confirmed the prognostic value of SHR in MI patients[ 5 ]. In patients with acute decompensated heart failure, those in the highest quintile of SHR (compared to those in the second quintile) were found to have a significantly higher risk of all-cause death (HR = 2.76, 95% CI 1.63–4.68), cardiovascular death (HR = 2.81, 95% CI 1.66–4.75), and heart failure rehospitalization (HR = 1.54, 95% CI 1.03–2.32) [ 6 ]. These findings highlight the prognostic significance of SHR in cardiovascular disease.

CS represents the most critical state of cardiovascular disease, and stress hyperglycemia is commonly observed in these patients, often associated with poor prognosis. Thoegersen et al. [17] found that CS patients with elevated glucose levels upon admission had an increased 30-day mortality. Similarly, in the IABP-SHOCK II trial, higher admission glucose concentrations were independently associated with 30-day and 1-year mortality [18], and this association was independent of the patient’s diabetic status What’s more, this association was independent of diabetic state [17, 18]. These studies highlight that glucose metabolism disorders are a significant pathophysiological factor in CS and are linked to worse outcomes. However, blood glucose levels are influenced by various factors, particularly chronic blood glucose conditions. In contrast, the SHR, which adjusts for average glycemic status, more accurately reflects the metabolic changes in critically ill patients under stress. SHR is a better biomarker of critical illness than absolute hyperglycemia [4]. However, the relationship between SHR and prognosis among CS patients are not well understood, and our study extended previous findings, suggesting SHR was an important predictor of poor prognosis in patients with CS.

The underlying mechanisms linking the SHR to outcomes in CS patients remain unclear, but several potential mechanisms may help explain this critical pathophysiological process. First, elevated SHR has been shown to be associated with circulatory disturbances and hypoperfusion. A sharp increase in blood glucose levels can trigger excessive production of reactive oxygen species by endothelial cells and the myocardium, leading to endothelial dysfunction, impaired vasodilation, and circulatory disorders [6]. Additionally, high blood glucose levels can activate platelets, inhibit fibrinolysis, and increase circulating adhesion molecules, which promote capillary leukocyte plugging and activate coagulation, further exacerbating circulatory disturbances and hypoperfusion [6, 19]. Second, inflammatory mediators, such as tumor necrosis factor-α, interleukin-1, interleukin-6, and C-reactive protein, contribute to stress hyperglycemia by inducing peripheral insulin resistance [9]. Therefore, stress hyperglycemia reflects the inflammatory response in CS patients, which, in turn, exacerbates hemodynamic disturbances, organ hypoperfusion, and cardiac dysfunction, ultimately leading to higher mortality [20]. Third, a high SHR is associated with the overactivation of the HPA axis and the sympathoadrenal system [3], which will lead to fluid retention, increased preload, and worsening pump failure [21]. Fourth, MI with left ventricular dysfunction remains the most frequent cause of CS [22]. Previous studies have shown that blood glucose levels are closely related to the degree of myocardial injury, as reflected by increased cardiac markers and reduced left ventricular function [23]. Moreover, several other mechanisms induced by hyperglycemia, such as impaired wound healing, increased infection risk, mitochondrial dysfunction, insulin resistance, electrolyte and fluid shifts, acid/base disturbances, immune dysregulation, lipotoxicity, catabolism of muscle and adipose tissue, and extracellular matrix deposition, collectively contribute to poor clinical outcomes [9]. Thus, the mechanisms by which SHR correlates with outcomes in CS patients are complex and multifactorial. These mechanisms often interact with one another, compounding their effects and worsening the prognosis.

The clinical implication of the present study is that the SHR should be carefully considered in patients with CS, particularly in those with MI complicated by CS, as demonstrated in our subgroup analysis. This analysis revealed that SHR was independently associated with 30-day and 360-day all-cause mortality in patients with AMI, but not in those without AMI. AMI as the underlying cause of CS not only leads to reduced perfusion of peripheral organs but also results in severe cardiac complications, such as heart failure, arrhythmias, and mechanical complications, which significantly increase the risk of mortality. Additionally, while it is not surprising that diabetic patients with elevated SHR have poor outcomes, previous studies, including our subgroup analysis, also showed that SHR affects the prognosis in non-diabetic patients. This finding suggests that SHR is a significant risk factor for prognosis in CS patients, regardless of their diabetic status.

The innovation of this study lies in its identification of the association between the SHR and prognosis in patients with CS. This is the first report to highlight the prognostic value of SHR in such patients, thereby extending previous research findings. Furthermore, since SHR more accurately reflects a patient’s glycemic metabolism, and prior studies have shown that its predictive value surpasses that of admission glucose levels [24], SHR may serve as a valuable prognostic marker for patients with CS.

In terms of managing stress hyperglycemia, intensive glycemic control in both ICU and non-ICU patients has not demonstrated clear clinical benefits [25,26,27]. This may suggest that SHR primarily reflects the severity of the disease rather than serving as a target for treatment. However, excessively elevated blood glucose levels still require management, as the RCS analyses showed that the risk of 30-day all-cause mortality increased significantly when SHR > 1.176. Previous studies have indicated that mild to moderate stress hyperglycemia may offer protective effects during stress and critical illness, while excessively high blood glucose can be harmful through various mechanisms, as previously mentioned [3, 9]. Therefore, SHR not only reflects disease severity but also provides valuable insights for optimizing treatment strategies in patients with CS.

There are several limitations to our study. First, it is a retrospective observational study with a relatively limited sample size. Despite using rigorous statistical methods, potential biases and uncontrolled factors may have influenced the outcomes. Therefore, large-scale prospective studies are needed for further clarification. Second, we focused solely on the impact of SHR on all-cause mortality, without considering other endpoints such as major cardiovascular adverse events, length of hospitalization, or hospitalization expenses, as these measures were not available in the MIMIC-IV dataset. Future prospective studies should include a broader range of clinical outcomes. Third, our study included CS patients from 2008 to 2022, a period during which management guidelines and interventions for CS were evolving. This may have affected our results, highlighting the need for contemporary clinical studies to validate our findings.