Extracardiac CKM phenotypes and early cardiorenal-systemic mortality risk after acute myocardial infarction

Abstract Background Acute myocardial infarction (AMI) represents established cardiovascular disease within the cardiovascular-kidney-metabolic (CKM) continuum, yet outcomes after the acute event vary widely. We examined whether extracardiac metabolic, renal, inflammatory, and nutritional patterns characterize clinically meaningful 365-day mortality risk in operational CKM stage 4-compatible AMI. Methods We analyzed a local AMI cohort and used MIMIC-IV for reduced-domain transportability. Glycemic, lipid, renal, and systemic inflammatory-nutritional abnormalities defined extracardiac CKM burden and phenotype architecture. The primary outcome was 365-day all-cause mortality. Cox models estimated burden- and phenotype-specific risk after adjustment for demographic factors and conventional AMI severity markers; sensitivity analyses examined phenotype allocation, renal-function boundaries, event timing, acute-severity adjustment, and exploratory metabolic, nutritional, and fibrosis markers. Results The local cohort included 3,312 operational CKM stage 4-compatible AMI patients; 3,173 with 147 deaths contributed to the primary Cox model. Complete 365-day observation was available for 3,309 patients (99.91%), and 149 of 153 deaths (97.38%) occurred within 90 days. Mortality increased stepwise with extracardiac CKM burden. Each 0.25 increment in burden was associated with higher 365-day mortality (adjusted HR 1.71, 95% CI 1.38–2.12; P < 0.001), with directionally consistent results in MIMIC-IV (HR 1.35, 95% CI 1.25–1.45; P < 0.001). Risk was highest when renal dysfunction co-occurred with systemic inflammatory-nutritional vulnerability: the renal-systemic multidomain phenotype had 15.24% mortality and an adjusted HR of 4.21 (95% CI 1.51–11.75; P = 0.006). In patients with exactly three abnormal domains, renal-systemic involvement had higher crude mortality than systemic-metabolic involvement (33/310 [10.6%] versus 12/651 [1.8%]), with attenuation after acute-severity adjustment (HR 1.79, 95% CI 0.81–3.98; P = 0.151). Conclusions Patients with operational CKM stage 4-compatible AMI showed marked prognostic variation. Extracardiac CKM burden and renal-systemic co-occurrence marked an early post-AMI high-risk pattern, supporting phenotype-aware risk characterization within established AMI.