Angiopoietin-like 4 protein is a long-term predictor of outcome in chest-pain patients with suspected acute coronary syndrome. (25th November 2020) - Aarsetoey, R
Abstract: Introduction: Angiopoietin-like 4 protein (ANGPTL4) has multiple physiological functions including modulation of angiogenesis, vascular permeability and lipid-metabolism. Acting as an inhibitor of lipoprotein lipase, ANGPTL4 has previously been found to be associated with lipid levels and risk of coronary artery disease. Purpose: To assess the prognostic value of ANGPTL4 for long-term outcome, in addition to conventional clinical risk factors, in chest-pain patients admitted with clinically suspected acute coronary syndrome (ACS). Methods: 1853 patients from Norway and Northern-Argentina were consecutively included in this prospective 2-center cohort study. ANGPTL4 concentrations were measured in 1829 admission-samples by enzyme immunoassay. Data were pooled for analysis. Multivariable Cox proportional-hazards models were fitted for the analysis of all-cause mortality, cardiac death and sudden cardiac death (SCD) within 24-months, comparing event rates across ANGPTL4-quartiles (Q1–4). Of patients with suspected ACS, 845 had a troponin T (TnT) value above the detection-limit. Subgroup analysis was performed for all-cause mortality in patients stratified according to TnT release >/≤0.01 ng/mL. Results: During 24-months follow-up, 254 patients (13.9%) died, of which 150 (8.2%) suffered cardiac death and 76 (4.2%) SCD. Patients who died had significantly higher admission-levels of ANGPTL4 compared to long-term survivors [4.99 (3.54–8.37) ng/mL versus 3.18 (2.14–4.78) ng/mL (median, 25 and 75% percentiles), p<0.001]. A stepwise increase in risk of all-cause death was seen with increasing quartiles of ANGPTL4, Figure 1. For cardiac death, ANGPTL4-levels in Q4 [Hazard Ratio (HR) 2.86 (95% confidence interval (CI); 1.10–7.45), p=0.031] as compared to Q1 were found to be an independent predictor of outcome. Similar results were seen for SCD in adjusted analysis for ANGPTL4-Q4 [HR 7.37 (95% CI: 1.75–31.1), p=0.007] as compared to Q1. In subgroup analysis, ANGPTL4 concentrations in the highest quartile were significantly associated with increased risk of all-cause mortality in patients with TnT-release [HR 2.07 (95% CI: 1.06–4.02), p=0.032], but not in patients without TnT-release. Conclusion: High admission-levels of ANGPTL4 were found to be an independent long-term predictor of all-cause mortality, cardiac death and SCD in patients with suspected ACS. Funding Acknowledgement: Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Regional Health Authority