Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice. (June 2018)

• Record Type: Journal Article
• Authors: Tuñón, José; Bäck, Magnus; Badimón, Lina; Bochaton-Piallat, Marie-Luce; Cariou, Bertrand; Daemen, Mat J; Egido, Jesus; Evans, Paul C; Francis, Sheila E; Ketelhuth, Daniel FJ; Lutgens, Esther; Matter, Christian M; Monaco, Claudia; Steffens, Sabine; Stroes, Erik; Vindis, Cécile; Weber, Christian; Hoefer, Imo E
• Is Part Of: European journal of preventive cardiology. Volume 25:Number 9(2018)
• Page Start: 948
• Page End: 955
• Publication Date: 2018-06
• Subjects: Lipids -- inflammation -- immune response -- atherosclerosis -- interleukin-1β -- canakinumab; Cardiovascular system -- Diseases -- Prevention -- Periodicals; Cardiac patients -- Rehabilitation -- Periodicals; 616.12
• DOI: 10.1177/2047487318773384
• Languages: English
• ISSNs: 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.