Joint association of stress hyperglycemia ratio and inflammatory-metabolic-coagulation profiles with long-term adverse outcomes in premature myocardial infarction

Background Despite the increasing incidence of premature myocardial infarction (PMI), the long-term prognostic significance of the stress hyperglycaemia ratio (SHR), particularly its combined effects with inflammatory, metabolic, and coagulation pathways, remains incompletely understood. Purpose This study aimed to investigate the association between the SHR and major adverse cardiovascular events (MACEs) in patients with PMI, and to evaluate the combined effects of SHR with inflammatory, metabolic, and coagulation biomarkers, as well as potential mediating mechanisms. Methods This prospective cohort study consecutively enrolled 1,691 patients with PMI admitted to the coronary care unit (CCU) of our Hospital between January 2015 and December 2024 (men ≤50 years, women ≤55 years).A data-driven approach was used to determine the optimal cutoff value of SHR, based on which patients were categorized into a SHR-L group (<1.128) and SHR-H group (≥1.128).The median follow-up duration was 1.38 years (IQR: 0.90–2.51), and the primary endpoint was the first occurrence of MACE.Kaplan–Meier survival analysis, Cox proportional hazards regression models, and restricted cubic spline analyses were applied to evaluate the association between SHR and long-term outcomes.Mediation analyses were further conducted to explore potential underlying mechanisms. Results During follow-up, 200 MACEs occurred (11.83%).Compared with the low-SHR group, patients with high SHR had a significantly increased risk of MACEs (adjusted HR, 1.776; 95% CI, 1.230–2.564; P = 0.002).Joint analyses demonstrated that the coexistence of high SHR with a high inflammatory state (hs-CRP ≥3 mg/L), obesity (BMI ≥28 kg/m²), insulin resistance (triglyceride–glucose index ≥9.2), elevated atherogenic lipoprotein burden (apoB ≥1.1 g/L), or a hypercoagulable state (D-dimer ≥0.5 mg/L) was associated with a synergistic increase in MACE risk.Among these combinations, patients with both high SHR and elevated D-dimer exhibited the highest risk (adjusted HR, 3.575; 95% CI, 2.174–5.880; P < 0.001).Mediation analyses indicated that the TyG index and D-dimer partially mediated the association between SHR and MACE, with mediation proportions of 32.93% and 6.58%, respectively. Conclusions Elevated SHR not only independently increases the risk of MACE in patients with premature myocardial infarction, but its concomitant presence with inflammatory, metabolic, and coagulation cascade abnormalities markedly amplifies this adverse prognostic risk. These findings underscore the incremental value of integrating SHR with multidimensional biomarkers for the prediction of long-term adverse outcomes.