Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice
Por:
Tunon, J, Back, M, Badimon, L, Bochaton-Piallat, ML, Cariou, B, Daemen, MJ, Egido, J, Evans, PC, Francis, SE, Ketelhuth, DFJ, Lutgens, E, Matter, CM, Monaco, C, Steffens, S, Stroes, E, Vindis, C, Weber, C, Hoefer, IE, ESC Working Grp Atherosclerosis
Publicada:
1 jun 2018
Resumen:
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)-1 blockade reduces the incidence of cardiovascular events in patients with previous myocardial infarction and C-reactive protein levels >2mg/L. These data confirm the connection between lipids and inflammation, as lipids activate the Nod-like receptor protein 3 inflammasome that leads to IL-1 activation. LDL-lowering drugs are the foundation of cardiovascular prevention. Now, the CANTOS trial demonstrates that combining them with IL-1 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-1 blockade. In addition, IL-1 blockade has only been studied in patients with C-reactive protein >2mg/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-1 pathway, reduces the cardiovascular risk. In this regard, the ongoing trials with methotrexate and colchicine may clarify whether the cardiovascular benefit of IL-1 blockade extends to other anti-inflammatory mechanisms. A positive result would represent a major change in the future treatment of atherosclerosis.
Filiaciones:
Tunon, J:
Univ Autonoma Madrid, Fdn Jimenez Diaz, Madrid, Spain
CiberCV, Madrid, Spain
Back, M:
Karolinska Univ Hosp, Stockholm, Sweden
Karolinska Inst, Stockholm, Sweden
Badimon, L:
Hosp Santa Creu & Sant Pau, Cardiovasc Sci Inst ICCC, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CiberCV, Barcelona, Spain
Bochaton-Piallat, ML:
Univ Geneva, Geneva, Switzerland
Cariou, B:
Univ Nantes, CNRS, CHU Nantes, Inst Thorax,INSERM, Nantes, France
Daemen, MJ:
Acad Med Ctr, Amsterdam, Netherlands
Egido, J:
Univ Autonoma Madrid, Fdn Jimenez Diaz, Madrid, Spain
CIBERDEM, Madrid, Spain
Evans, PC:
Univ Sheffield, Sheffield, S Yorkshire, England
Francis, SE:
Univ Sheffield, Sheffield, S Yorkshire, England
Ketelhuth, DFJ:
Karolinska Inst, Stockholm, Sweden
Lutgens, E:
Acad Med Ctr, Amsterdam, Netherlands
Univ Amsterdam, Amsterdam, Netherlands
LMU Munich & German Ctr Cardiovasc Res DZHK, Inst Cardiovasc Prevent, Partner Site Munich Heart Alliance, Munich, Germany
Matter, CM:
Univ Hosp Zurich, Univ Heart Ctr, Zurich, Switzerland
Univ Zurich, Ctr Mol Cardiol, Zurich, Switzerland
Monaco, C:
Univ Oxford, Kennedy Inst, NDORMS, Oxford, England
Steffens, S:
LMU Munich & German Ctr Cardiovasc Res DZHK, Inst Cardiovasc Prevent, Partner Site Munich Heart Alliance, Munich, Germany
Stroes, E:
Acad Med Ctr, Amsterdam, Netherlands
Vindis, C:
Inst Metab & Cardiovasc Dis, INSERM, UMR 1048, Toulouse, France
Weber, C:
LMU Munich & German Ctr Cardiovasc Res DZHK, Inst Cardiovasc Prevent, Partner Site Munich Heart Alliance, Munich, Germany
Maastricht Univ, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands
Hoefer, IE:
Univ Med Ctr Utrecht, Utrecht, Netherlands
Bronze, Green Accepted, Green Published
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