Cardiac troponin elevations and risk of major adverse cardiovascular events in five non-cardiac diseases

Background Cardiac troponins (cTn) are biomarkers of myocardial injury and a cornerstone in the diagnosis of acute coronary syndrome (ACS); However, cTn elevations are frequently observed in non-cardiac diseases and have been associated with adverse outcomes. The prognostic implications and differences between high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) remain incompletely understood. Data on the comparative prognostic performance of cTnT and cTnI across disease states in patients with paired measurements are limited. Purpose To investigate the prevalence and prognostic value of hs-cTnT and hs-cTnI in five non-cardiac disease groups and to compare their relative prognostic performance. Methods We prospectively included patients with five non-cardiac conditions: chronic kidney disease stage 5 (CKD5), rhabdomyolysis, sepsis, stroke, and major orthopedic surgery, over a 1.5-year period. Patients were enrolled within 48 hours of admission and underwent ECG, echocardiography, and measurement of hs-cTnT and hs-cTnI . The primary endpoint was major adverse cardiovascular events (MACE) defined as all-cause mortality, myocardial infarction, or stroke. Secondary endpoints included prevalence of cTn elevation defined as >99th percentile. Cox proportional hazards models were used to evaluate associations between cTn levels and MACE. cTn concentrations were log2-transformed to model risk per doubling, with analyses performed separately and with mutual adjustment for the other troponin. Results Among 226 patients (mean age 73.6±14.1 years; 49.6% female), 166 (73.5%) had hs-cTnT above the sex-specific 99th percentile compared with 45 (19.9%) with elevated hs-cTnI (p<0.001). Distribution of cTn elevations across disease groups are shown in fig 1. During a median follow-up of 1.44 years (IQR 1.09–1.86; reverse Kaplan–Meier), 29 patients (12.8%) experienced MACE: 25 (11.1%) died, 7 (3.1%) had a stroke, and none had myocardial infarction. In the overall cohort, both hs-cTnT and hs-cTnI were associated with incident MACE in separate models (hs-cTnT: HR 1.33 [1.15–1.54]; hs-cTnI: HR 1.13 [1.03–1.24] per doubling). In mutually adjusted models, hs-cTnT remained independently associated with MACE (HR 1.36 [1.10–1.69]), whereas hs-cTnI did not (HR 0.98 [0.86–1.12]) (fig 2). In subgroup analyses, the associations differed across disease groups. In CKD5, hs-cTnT was associated with MACE (HR 2.21 [1.33–3.67]), whereas in stroke, hs-cTnI was (HR 1.98 [1.10–3.56]) and hs-cTnT was not. Conclusion In patients with non-cardiac diseases, hs-cTnT elevations were significantly more prevalent than hs-cTnI elevations. Both cTnI and cTnT were associated with subsequent MACE. Notably, hs-cTnT and hs-cTnI demonstrated differential prognostic patterns across disease states, suggesting distinct underlying mechanisms of myocardial injury and supporting a disease-specific interpretation of troponin elevations beyond ACS.Figure 1Figure 2