The prognostic significance of stress hyperglycemia ratio in evaluating all-cause and cardiovascular mortality risk among individuals across stages 0-3 of cardiovascular-kidney-metabolic syndrome: evidence from two cohort studies.

Abstract

Background: The American Heart Association (AHA) proposed the concept of cardiovascular-kidney-metabolic (CKM) syndrome, underscoring the interconnectedness of cardiovascular, renal, and metabolic diseases. The stress hyperglycemia ratio (SHR) represents an innovative indicator that quantifies blood glucose fluctuations in patients experiencing acute or subacute stress, correlating with detrimental clinical effects. Nevertheless, the prognostic significance of SHR within individuals diagnosed with CKM syndrome in stages 0 to 3, particularly with respect to all-cause or cardiovascular disease (CVD) mortality risks, has not been fully understood yet.

Methods: The current study analyzed data from 9647 participants with CKM syndrome, covering stages 0 to 3, based on the NHANES (National Health and Nutrition Examination Survey) collected from 2007 to 2018. In this study, the primary exposure variable was the SHR, computed as fasting plasma glucose divided by (1.59 * HbA1c - 2.59). The main endpoints of study were all-cause mortality as well as CVD mortality, with death registration data sourced through December 31, 2019. The CHARLS database (China Health and Retirement Longitudinal Study) was utilized as validation to enhance the reliability of the findings.

Results: This study included 9647 NHANES participants, who were followed for a median duration of 6.80 years. During this period, 630 all-cause mortality cases and 135 CVD-related deaths in total were recorded. After full adjustment for covariates, our results displayed a robust positive association of SHR with all-cause mortality (Hazard ratio [HR] = 1.09, 95% Confidence interval [CI] 1.04-1.13). However, the SHR exhibited no significant relationship with CVD mortality (HR = 1.00, 95% CI 0.91-1.11). The mediation analysis results suggested that the relationship between SHR and all-cause mortality risk is partially mediated by RDW, albumin, and RAR. Specifically, the mediating effects were - 17.0% (95% CI - 46.7%, - 8.7%), - 10.1% (95% CI - 23.9%, - 4.7%), and - 23.3% (95% CI - 49.0%, - 13.0%), respectively. Additionally, analyses of the CHARLS database indicated a significant positive correlation between SHR and all-cause mortality among individuals diagnosed with CKM across stages 0-3 during the follow-up period from 2011 to 2020.

Conclusions: An increased SHR value is positively associated with an elevated likelihood of all-cause mortality within individuals diagnosed with CKM syndrome across stages 0-3, yet it shows no significant association with CVD mortality. SHR is an important tool for predicting long-term adverse outcomes in this population. Cardiovascular-kidney-metabolic (CKM) syndrome emphasizes the interconnectedness of cardiovascular, kidney, and metabolic diseases. The stress hyperglycemia ratio (SHR) is a novel marker reflecting stress-induced glucose fluctuations, but its prognostic value in individuals with CKM syndrome (stages 0-3) remains uncertain. This study explores the association between SHR and all-cause and cardiovascular disease (CVD) mortality in this population. Our findings indicate that SHR is significantly associated with an increased risk of all-cause mortality (HR = 1.09, 95% CI 1.04-1.13), but not with CVD mortality (HR = 1.00, 95% CI: 0.91-1.11). Mediation analysis results suggested that the relationship between SHR and all-cause mortality risk is partially mediated by RDW, albumin, and RAR. Specifically, the mediating effects were - 17.0% (95% CI - 46.7%, - 8.7%), - 10.1% (95% CI - 23.9%, - 4.7%), and - 23.3% (95% CI - 49.0%, - 13.0%), respectively. Validation using the CHARLS database supports these findings. These results suggest that SHR could serve as a prognostic biomarker for long-term mortality risk in CKM patients, offering potential clinical utility in risk stratification and management.