Serum sodium-to-chloride ratio and 365-day mortality after acute myocardial infarction: a dual-cohort study

Abstract

Abstract Background Early disturbances in sodium–chloride homeostasis may reflect systemic illness severity after acute myocardial infarction (AMI), but the prognostic value of the serum sodium-to-chloride (Na/Cl) ratio remains incompletely defined. Methods We performed a retrospective dual-cohort study using a hospital-based clinical cohort of patients with acute myocardial infarction and an independent MIMIC-IV intensive care cohort. The early serum sodium-to-chloride ratio was calculated from admission laboratory measurements in the clinical cohort and from measurements obtained within the first 24 h after ICU admission in MIMIC-IV. The primary outcome was 365-day all-cause mortality. Multivariable Cox proportional hazards models were used to estimate the association between sodium-to-chloride ratio and mortality, with the ratio analyzed as both a continuous variable and according to clinically derived quartiles. Non-linear associations were examined using restricted cubic splines. Model performance and robustness were further evaluated using discrimination analyses, fixed-time logistic regression, inverse-probability weighting, and landmark analyses among 30-day survivors. Results In the clinical cohort, 3,091 patients were included with 139 deaths at 365 days, of which 130 occurred within 30 days. A higher Na/Cl ratio was associated with increased mortality risk (HR per 0.01 increase: 1.16, 95% CI 1.12–1.21; HR per 1-SD increase: 1.72, 95% CI 1.49–1.98). Patients in the highest quartile had higher mortality than those in the combined lower three quartiles (HR 2.27, 95% CI 1.62–3.19). In the MIMIC-IV ICU cohort ( n = 6,019; 1,965 deaths), the association was directionally consistent but attenuated (HR per 0.01 increase: 1.05, 95% CI 1.05–1.06; HR per 1-SD increase: 1.35, 95% CI 1.30–1.40). Restricted cubic spline analyses suggested nonlinear associations in both cohorts, and sensitivity analyses supported the overall direction of the findings. Conclusions A higher early serum Na/Cl ratio was associated with increased 365-day mortality after AMI and showed directional reproducibility in an external ICU cohort. The association in the clinical cohort was largely driven by early deaths. The Na/Cl ratio may serve as a readily available adjunctive marker of electrolyte-homeostasis disturbance and systemic vulnerability after AMI.