Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice
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 red...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
SAGE Publications
2018
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| _version_ | 1826276104793489408 |
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| author | Tuñón, J Bäck, M Badimón, L Bochaton-Piallat, M-L Cariou, B Daemen, MJ Egido, J Evans, PC Francis, SE Ketelhuth, DF Lutgens, E Matter, CM Monaco, C Steffens, S Stroes, E Vindis, C Weber, C Hoefer, IE |
| author_facet | Tuñón, J Bäck, M Badimón, L Bochaton-Piallat, M-L Cariou, B Daemen, MJ Egido, J Evans, PC Francis, SE Ketelhuth, DF Lutgens, E Matter, CM Monaco, C Steffens, S Stroes, E Vindis, C Weber, C Hoefer, IE |
| author_sort | Tuñón, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:08:58Z |
| format | Journal article |
| id | oxford-uuid:64d1b788-881a-4baa-b720-3ebc6597fe8e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:08:58Z |
| publishDate | 2018 |
| publisher | SAGE Publications |
| record_format | dspace |
| spelling | oxford-uuid:64d1b788-881a-4baa-b720-3ebc6597fe8e2022-03-26T18:21:22ZInterplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practiceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:64d1b788-881a-4baa-b720-3ebc6597fe8eEnglishSymplectic Elements at OxfordSAGE Publications2018Tuñón, JBäck, MBadimón, LBochaton-Piallat, M-LCariou, BDaemen, MJEgido, JEvans, PCFrancis, SEKetelhuth, DFLutgens, EMatter, CMMonaco, CSteffens, SStroes, EVindis, CWeber, CHoefer, IEDyslipidaemia 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. |
| spellingShingle | Tuñón, J Bäck, M Badimón, L Bochaton-Piallat, M-L Cariou, B Daemen, MJ Egido, J Evans, PC Francis, SE Ketelhuth, DF Lutgens, E Matter, CM Monaco, C Steffens, S Stroes, E Vindis, C Weber, C Hoefer, IE Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title | Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title_full | Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title_fullStr | Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title_full_unstemmed | Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title_short | Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice |
| title_sort | interplay between hypercholesterolaemia and inflammation in atherosclerosis translating experimental targets into clinical practice |
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