Gregersen, I., Michelsen, A.E., Lunde, N.N. et al. (17 more authors) (2020) Legumain in acute coronary syndromes: A substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Journal of the American Heart Association, 9 (17). e016360. ISSN 2047-9980
Abstract
Background
The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome.
Methods and Results
Serum levels of legumain were analyzed in 4883 patients with acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow‐up. Associations between legumain and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04–1.21), P=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02–1.19; P=0.013) but not in the fully adjusted model. Legumain levels at 1 month were not associated with the composite end point but were negatively associated with stroke (HR, 0.62; 95% CI, 0.44–0.88; P=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37–0.88; P=0.0114).
Conclusions
Baseline legumain was associated with the primary outcome in patients with acute coronary syndrome, but not in the fully adjusted model. The association between high levels of legumain at 1 month and decreased occurrence of stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of legumain during atherogenesis and acute coronary syndrome.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00391872.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, (https://creativecommons.org/licenses/by-nc-nd/4.0/) which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
Keywords: | legumain; acute coronary syndromes; ischemic stroke |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Oct 2020 10:20 |
Last Modified: | 05 Oct 2020 10:20 |
Status: | Published |
Publisher: | Ovid Technologies (Wolters Kluwer Health) |
Refereed: | Yes |
Identification Number: | 10.1161/jaha.120.016360 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:165612 |