TY - JOUR
T1 - Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice
AU - Tunon, Jose
AU - Back, Magnus
AU - Badimon, Lina
AU - Bochaton-Piallat, Marie-Luce
AU - Cariou, Bertrand
AU - Daemen, Mat J.
AU - Egido, Jesus
AU - Evans, Paul C.
AU - Francis, Sheila E.
AU - Ketelhuth, Daniel F. J.
AU - Lutgens, Esther
AU - Matter, Christian M.
AU - Monaco, Claudia
AU - Steffens, Sabine
AU - Stroes, Erik
AU - Vindis, Cecile
AU - Weber, Christian
AU - Hoefer, Imo E.
AU - ESC Working Grp Atherosclerosis
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Lipids
KW - inflammation
KW - immune response
KW - atherosclerosis
KW - interleukin-1
KW - canakinumab
KW - C-REACTIVE PROTEIN
KW - FACTOR-KAPPA-B
KW - RANDOMIZED CONTROLLED-TRIAL
KW - CORONARY-ARTERY-DISEASE
KW - CARDIOVASCULAR EVENTS
KW - RHEUMATOID-ARTHRITIS
KW - MONOCLONAL-ANTIBODIES
KW - SECONDARY ANALYSIS
KW - NATIONWIDE COHORT
KW - STATIN THERAPY
U2 - 10.1177/2047487318773384
DO - 10.1177/2047487318773384
M3 - Article
C2 - 29759006
SN - 2047-4873
VL - 25
SP - 948
EP - 955
JO - European Journal of Preventive Cardiology
JF - European Journal of Preventive Cardiology
IS - 9
ER -