Angiopoietin like 4 (ANGPTL4) protein challenges brain natriuretic peptide (BNP) as a prognostic biomarker in patients admitted with chest pain of suspected coronary origin

Background BNP is predominantly synthesized in the ventricular myocardium and is released into the circulation in response to ventricular distention in heart failure and secondary to ventricular dysfunction in an acute coronary syndrome (ACS). ANGPTL4 is an important modulator of lipid metabolism and is involved in the regulation of vascular integrity and angiogenesis. Elevated levels of both biomarkers play a pivotal role in cardiovascular disease and serve as prognostic indicators of ACS and heart failure. Their prognostic significance has previously been explored [1]. Aims To assess the prognostic weighting in ACS of ANGPTL4 and BNP in a crosscontinental setting. Methods Patients admitted with chest pain of suspected coronary origin were recruited in Norway and Argentina, applying similar protocols, and matched by propensity scoring according to age, sex and use of statins, yielding 507 subjects in each group. A Cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for standardized logANGPTL4 and logBNP, respectively, with all-cause mortality within 5 years as the dependent variable. Multivariable analysis was performed for the assessment of the hazard ratio (HR) 95% confidence interval (95%CI). Receiver Operating Characteristics (ROC) for calculation of Area Under Curve (AUC) (95%CI) was performed in the combined populations for evaluation of crosscontinental biomarker utility. Results There was no significant difference in death rates at 5 years follow-up in the Argentinian (20.1%) and Norwegian (22.7%) cohort of patients, p=0.32. In the multivariable adjusted analysis, ANGPTL4 was independently associated with all-cause mortality in each cohort: [HR 1.65 (95%CI 1.35-2.01), p<0.001] and [HR 1.30 (95%CI 1.07-1.57), p=0.008], respectively. The corresponding results for BNP were: [HR 1.61 (95%CI 1.28-2.04), p<0.001] and [HR 1.65 (95%CI 1.29-2.10), p<0.001]. AUC for ANGPTL4 in both populations combined was 0.718 (95%CI 0.680-0.756) and for BNP 0.730 (95%CI 0.691-0.769). Conclusion In the Argentinian cohort, ANGPTL4 carries the same risk for 5-years’ mortality as BNP does in the Norwegian cohort (Z=0.004; p= 0.997). In the combined population, BNP performs better than ANGPTL4 as judged by the AUC in the ROC analysis.