Angiopoietin-like 4 protein is a long-term predictor of outcome in chest-pain patients with suspected acute coronary syndrome

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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. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Regional Health Authority