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Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A CLARICOR trial sub-study
Department of Emergency Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.ORCID iD: 0000-0001-6113-0472
Department of Cardiology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark..
Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark..
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2019 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 284, p. 202-208Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.

METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).

RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).

CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.

Place, publisher, year, edition, pages
2019. Vol. 284, p. 202-208
Keywords [en]
Cardiovascular, Endostatin, Epidemiology, Extracellular matrix, Mortality
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-382572DOI: 10.1016/j.atherosclerosis.2019.02.031ISI: 000466155400027PubMedID: 30959314OAI: oai:DiVA.org:uu-382572DiVA, id: diva2:1307445
Funder
Swedish Research CouncilSwedish Heart Lung FoundationMarianne and Marcus Wallenberg FoundationThuréus stiftelse för främjande av geriatrisk forskningAvailable from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-06-18Bibliographically approved

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Carlsson, Axel C.Larsson, Anders

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