Angiopoietin-Like 4 (ANGPTL4) Protein and Its Relation to Lipids Challenges the Prognostic Performance of B-Type Natriuretic Peptide (BNP) Transcontinentally in Patients with Suspected Coronary Chest Pain, Suggesting Their Combined Use in Risk Prediction

BNP is predominantly synthesized in the ventricular myocardium in response to ventricular distension. ANGPTL4 modulates lipid metabolism, vascular integrity and angiogenesis. Both biomarkers serve as prognostic indicators in acute coronary syndrome (ACS). The purpose of this study is to compare the prognostic weighting of ANGPTL4 with BNP in a cross-continental setting and to assess the former’s association with circulating lipids in patients with suspected coronary chest pain. Patients were recruited in Norway (NOR) and Argentina (ARG) and matched exactly by propensity scoring according to age, sex and previous use of statins, yielding 507 subjects in each group. Cox regression models were fitted for standardized log_e ANGPTL4 and log_e BNP, respectively, with all-cause mortality within 5 years as the dependent variable. Receiver Operating Characteristic (ROC) analysis was applied for the area under curve (AUC). Death rates were similar: (ARG = 20.1%) and (NOR = 22.7%), p = 0.320. ANGPTL4 and BNP were independently associated with all-cause mortality in each cohort. Concentrations of ANGPTL4 and triglycerides (TG) were higher, and total cholesterol (TC), LDL-C and HDL-C were lower in ARG compared to NOR (each p < 0.001). ANGPTL4 correlated negatively with each lipid fraction and positively with C-reactive protein (CRP) but did not correlate with body mass index (BMI) in the cohorts combined. AUC for ANGPTL4 outperformed BNP in ARG, and the reverse was observed in NOR. However, AUC for ANGPTL4 in the combined cohorts was 0.718 (95%CI 0.680–0.756) and for BNP it was 0.730 (95%CI 0.691–0.769). Their different pathogenic pathways may improve prognostic information, with a pattern that may differ between continents.