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Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome
Authors:Reidun Aarsetøy  Thor Ueland  Pål Aukrust  Annika E Michelsen  Ricardo Leon de la Fuente  Volker Pönitz  Trygve Brügger-Andersen  Heidi Grundt  Harry Staines  Dennis WT Nilsen
Institution:1. Department of Cardiology, Stavanger University Hospital, Stavanger, Norway;2. Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway;3. Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway

Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway;4. Centro Cardiovascular Salta, Salta, Argentina;5. Department of Clinical Science, University of Bergen, Bergen, Norway

Department of Respiratory Medicine, Stavanger University Hospital, Stavanger, Norway;6. Sigma Statistical Services, Balmullo, UK;7. Department of Cardiology, Stavanger University Hospital, Stavanger, Norway

Department of Clinical Science, University of Bergen, Bergen, Norway

Abstract:

Background

Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982).

Methods

A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables.

Results

At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08–1.50) for Norway, and HR 1.57 (95% CI, 1.27–1.95) for Argentina], with similar results at 60 months HR 1.19 (95% CI, 1.05–1.35) (Norway), and HR 1.56 (95% CI, 1.30–1.88) (Argentina)], and was also significantly associated with cardiac death HR 1.51 (95% CI, 1.14–2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months HR 1.39 (95% CI, 1.15–1.68)] and at 60 months HR 1.43 (95% CI, 1.23–1.67)], enforcing trends in the Norwegian population.

Conclusions

ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.
Keywords:acute coronary syndrome  all-cause mortality  angiopoietin-2  angiopoietin-like 4 protein  prognostic biomarkers  cardiac death
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