University of Oulu

Lin, R., Junttila, J., Piuhola, J. et al. Endothelin-1 is associated with mortality that can be attenuated with high intensity statin therapy in patients with stable coronary artery disease. Commun Med 3, 87 (2023).

Endothelin-1 is associated with mortality that can be attenuated with high intensity statin therapy in patients with stable coronary artery disease

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Author: Lin, Ruizhu1; Junttila, Juhani1,2,3; Piuhola, Jarkko1;
Organizations: 1Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
2Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
Persistent link:
Language: English
Published: Springer Nature, 2023
Publish Date: 2023-09-27


Background: All coronary artery disease (CAD) patients do not benefit equally of secondary prevention. Individualized intensity of drug therapy is currently implemented in guidelines for CAD and diabetes. Novel biomarkers are needed to identify patient subgroups potentially benefitting from individual therapy. This study aimed to investigate endothelin-1 (ET-1) as a biomarker for increased risk of adverse events and to evaluate if medication could alleviate the risks in patients with high ET-1.

Methods: A prospective observational cohort study ARTEMIS included 1946 patients with angiographically documented CAD. Blood samples and baseline data were collected at enrollment and the patients were followed for 11 years. Multivariable Cox regression was used to assess the association between circulating ET-1 level and all-cause mortality, cardiovascular (CV) death, non-CV death and sudden cardiac death (SCD).

Results: Here we show an association of circulating ET-1 level with higher risk for all-cause mortality (HR: 2.06; 95% CI 1.5–2.83), CV death, non-CV death and SCD in patients with CAD. Importantly, high intensity statin therapy reduces the risk for all-cause mortality (adjusted HR: 0.05; 95% CI 0.01–0.38) and CV death (adjusted HR: 0.06; 95% CI 0.01–0.44) in patients with high ET-1, but not in patients with low ET-1. High intensity statin therapy does not associate with reduction of risk for non-CV death or SCD.

Conclusions: Our data suggests a prognostic value for high circulating ET-1 in patients with stable CAD. High intensity statin therapy associates with reduction of risk for all-cause mortality and CV death in CAD patients with high ET-1.

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Series: Communications medicine
ISSN: 2730-664X
ISSN-E: 2730-664X
ISSN-L: 2730-664X
Volume: 3
Issue: 1
Article number: 87
DOI: 10.1038/s43856-023-00322-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Academy of Finland [grant number 333349 to J.J. and grant number 297094 and 333284 to R.K.]; Finnish Foundation for Cardiovascular Research [to R.L., J.J., H.H., M.T. and R.K.]; by Jane and Aatos Erkko Foundation [to J.J., H.H. and R.K.] and the Sigrid Juselius Foundation (to J.J., H.H. and R.K.) and Business Finland [to M.T.].
Academy of Finland Grant Number: 333349
Detailed Information: 333349 (Academy of Finland Funding decision)
297094 (Academy of Finland Funding decision)
333284 (Academy of Finland Funding decision)
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