Tunon, J., Back, M., Badimon, L. et al. (16 more authors) (2018) Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice. European Journal of Preventive Cardiology, 25 (9). pp. 948-955. ISSN 2047-4873
Abstract
Dyslipidaemia and inflammation are closely interconnected in their contribution to atherosclerosis. In fact, low-density lipoprotein (LDL)-lowering drugs have anti-inflammatory effects. The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) has shown that interleukin (IL)-1β blockade reduces the incidence of cardiovascular events in patients with previous myocardial infarction and C-reactive protein levels >2 mg/L. These data confirm the connection between lipids and inflammation, as lipids activate the Nod-like receptor protein 3 inflammasome that leads to IL-1β activation. LDL-lowering drugs are the foundation of cardiovascular prevention. Now, the CANTOS trial demonstrates that combining them with IL-1β blockade further decreases the incidence of cardiovascular events. However, both therapies are not at the same level, given the large evidence showing that LDL-lowering drugs reduce cardiovascular risk as opposed to only one randomized trial of IL-1β blockade. In addition, IL-1β blockade has only been studied in patients with C-reactive protein >2 mg/L, while the benefit of LDL-lowering is not restricted to these patients. Also, lipid-lowering drugs are not harmful even at very low ranges of LDL, while anti-inflammatory therapies may confer a higher risk of developing fatal infections and sepsis. In the future, more clinical trials are needed to explore whether targeting other inflammatory molecules, both related and unrelated to the IL-1β pathway, reduces the cardiovascular risk. In this regard, the ongoing trials with methotrexate and colchicine may clarify whether the cardiovascular benefit of IL-1β blockade extends to other anti-inflammatory mechanisms. A positive result would represent a major change in the future treatment of atherosclerosis.
Metadata
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Copyright, Publisher and Additional Information: | © 2018 The European Society of Cardiology. This is an author-produced version of a paper subsequently published in European Journal of Preventive Cardiology. Uploaded in accordance with the publisher's self-archiving policy. | ||||
Keywords: | Lipids; inflammation; immune response; atherosclerosis; interleukin-1β; canakinumab | ||||
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Institution: | The University of Sheffield | ||||
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals | ||||
Funding Information: |
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Depositing User: | Symplectic Sheffield | ||||
Date Deposited: | 23 Apr 2019 13:45 | ||||
Last Modified: | 14 May 2019 00:40 | ||||
Status: | Published | ||||
Publisher: | SAGE Publications | ||||
Refereed: | Yes | ||||
Identification Number: | https://doi.org/10.1177/2047487318773384 | ||||
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