ObjectiveTo investigate the association between the stress-induced hyperglycemia ratio (SHR) and all-cause, cardiovascular, and diabetes-related mortality in patients with advanced cardiovascular-kidney-metabolic (CKM) syndrome, and to evaluate the value of SHR as an independent prognostic marker. MethodsThis retrospective cohort study used data from the 1999–2018 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 2 135 patients with advanced CKM (stages 3 and 4) were included. Kaplan-Meier analysis and multivariable Cox regression models were applied to assess the relationship between SHR and mortality outcomes. Restricted cubic spline (RCS) analysis was employed to explore potential non-linear associations. Subgroup analyses were conducted to identify possible effect modifiers. ResultsOver a mean follow-up of 248 months, 674 all-cause, 198 cardiovascular, and 31 diabetes-related deaths occurred. Elevated SHR was significantly associated with diabetes-related mortality (HR=3.48, P<0.001) in a dose-response manner. SHR exhibited a U-shaped relationship with both all-cause and cardiovascular mortality (non-linearity P<0.001), indicating increased risk at both low and high SHR levels. Subgroup analyses revealed that sex, BMI, and hyperlipidemia significantly modified the association between SHR and diabetes-related death. ConclusionSHR is an independent predictor of mortality risk in patients with advanced CKM syndrome, particularly for diabetes-related death. These findings support the integration of SHR into risk stratification of high-risk CKM populations and provide a basis for metabolic stress-targeted interventions.
ObjectiveTo explore therapeutic mechanisms and clinical application prospects of novel weight-loss medications in patients with obesity complicated by cardiovascular-kidney-metabolic (CKM) syndrome, aiming to provide theoretical support and therapeutic strategies for personalized precision management of CKM syndrome. MethodsRecent domestic and international studies were retrospectively reviewed, focusing on the mechanisms of action, clinical research outcomes, and application progress of novel weight-loss medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 receptor agonists, triple GIP/GLP-1/glucagon receptor agonists, and amylin analogues. Special emphasis was placed on their comprehensive effects on cardiovascular, renal, and metabolic parameters. ResultsNovel weight-loss medications have demonstrated significant weight reduction and multisystem benefits through precise regulation of central appetite pathways, insulin sensitivity, and lipid metabolism. Among these medications, GLP-1 receptor agonists (e.g., semaglutide) and dual receptor agonists (e.g., tirzepatide) have been confirmed in phase Ⅲ clinical trials to effectively reduce cardiovascular event risks, slow renal function deterioration, and markedly improve glycemic control in obese patients with CKM syndrome. Triple receptor agonists (e.g., retatrutide) and combination medication regimen (e.g., CagriSema regimen) have further enhanced weight-loss efficacy, providing novel therapeutic avenues for obesity-related diseases. Additionally, these medications usually require combined application with traditional chronic disease medications, such as sodium-glucose linked transporter 2 inhibitors and renin-angiotensin-aldosterone system blockers, to achieve comprehensive therapeutic outcomes in CKM syndrome patients. However, further studies are needed to address long-term safety in real-world settings, optimization of drug formulations, and application in precision medicine. ConclusionsNovel weight-loss medications offer promising strategies for personalized precision treatment of obesity with CKM syndrome due to their significant weight-loss efficacy and multisystem synergistic effects. Although current clinical trials demonstrate substantial therapeutic potential, the complexity of CKM syndrome and individual patient variability necessitate additional in-depth research to facilitate broader clinical adoption and optimization of these medications.