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Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice

Tuñón, José
Bäck, Magnus
Badimón, Lina
Cariou, Bertrand
Daemen, Mat J
Egido, Jesus
Evans, Paul C
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Published in European Journal of Preventive Cardiology. 2018, vol. 25, no. 9, p. 948-955
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.
PMID: 29759006
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Research group Bochaton-Piallat Marie-Luce (pathologie et immunologie) (646)
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TUÑÓN, José et al. Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice. In: European Journal of Preventive Cardiology, 2018, vol. 25, n° 9, p. 948-955. doi: 10.1177/2047487318773384 https://archive-ouverte.unige.ch/unige:112028

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Deposited on : 2018-12-05

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