#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
CS
proLékaře.cz / Journals / Diabetes a obezita / 2019 - 37

Anti-inflammatory treatment reduces atherothrombotic risks

Czech version

Authors: Ján Murín 1;  Jozef Bulas 1;  Martin Wawruch 2
Authors‘ workplace: I. interná klinika LF UK a UNB, Nemocnica Staré Mesto, Bratislava 1;  Ústav farmakológie a klinickej farmakológie LF UK, Bratislava 2
Published in: Diab Obez 2019; 19(37): 32-37
Category:

Overview

Important cardiovascular (CV) events occur despite control of conventional risk factors. Inflammation, measured by hsCRP concentration, is associated with future CV events in both primary and secondary prevention, independent of usual risk factors and markers. Statins are powerful lipid-lowering agents with clinically relevant anti-inflammatory effects. Some recent data support targeting the interleukin (IL) IL1→IL6→CRP signaling pathway as an adjunctive method for atheroprotection. The CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial showed that reducing inflammation through IL1beta inhibition significantly reduced CV risk, beyond that achievable with lipid lowering. The CANTOS study further demonstrated a 31 % reduction in CV and also all-cause mortalities among patients treated with canakinumab who achieved the largest reductions in hsCRP as well as an efficacy in high-risk patients with chronic kidney disease and diabetes.

This review outlines the clinical implications of mentioned study and focuses on the treatment of “residual inflammatory risk”.

Received 28. 3. 2019

Accepted 18. 4. 2019

Keywords:

canakinumab – cardiovascular disease – interleukin 1 beta – vascular inflammation – CANTOS study

Sources

  1. Ridker PM. A test in context: high-sensitivity C-reactive protein. J Am Coll Cardiol 2016; 67(6): 712–723. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2015.11.037>.

  2. Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in „active“ coronary artery disease. Am J Cardiol 1990; 65(3): 168–172

  3. Ridker PM, Cushman M, Stampfer MJ et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336(14): 973–979. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM199704033361401>.

  4. Ridker PM, Rifai N, Pfeffer MA et al. [Cholesterol and Recurrent Events (CARE) investigators]. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998; 98(9): 839–844.

  5. Ridker PM, Rifai N, Clearfield M et al. [Airforce/Texas Coronary Atherosclerosis Prevention Study Investigators]. Measurement of C-reactive protein for targeting statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344(26): 1959–1865. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM200106283442601>.

  6. Libby P. Interleukin-1 beta as a target for atherosclerosis therapy. Biological basis of CANTOS and beyond. J Am Coll Cardiol 2017; 70(18): 2278–2289. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2017.09.028>.

  7. Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 2016; 118(1): 145–156. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCRESAHA.115.306656>.

  8. Ridker PM, Everett B, Thuren T et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377(12): 1119–1131. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1707914>.

  9. Ridker PM, Hennekens CH, Buring JE et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342(12): 836–843. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM200003233421202>.

  10. Ridker PM, Danielson E, Fonseca FA et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reative protein. N Engl J Med 2008; 359(21): 2195–2207. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0807646>.

  11. Braumwald E. Creating controversy where none exists: the important role of C-reactive protein in the CARE, AFCAPS/TexCAPS, PROVE IT, REVERSAL, A to Z, JUPITER, HEART PROTECTION, and ASCOT trials. Eur Heart J 2012; 33(4): 430–432. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehr310>.

  12. Yuen JY, Levine RA, Mantadilok V et al. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000; 35(3): 469–476.

  13. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372(25): 2387–2397. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1410489>.

  14. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713–1722. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1615664>.

  15. Ridker PM, Revkin J, Amarenco P et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Eng J Med 2017; 376(16): 1527–1539. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1701488>.

  16. Murín J, Čaprnda M, Kasperová V. Čo priniesla klinická štúdia ODYSSEY OUTCOMES. Cardiol Lett 2018; 27(2): 62–67.

  17. Ridker PM. How common is residual inflammatory risk? Circ Res 2017; 120(4): 617–619. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCRESAHA.116.310527>.

  18. Bohula EA, Giugliano RP, Leiter LA et al. Inflammatory and cholesterol risk in the FOURIER trial. Circulation 2018; 138(2): 131–140. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034032>.

  19. Pradhan A, Aday AW, Rose LM et al. Residual inflammatory risk on treatment with PCSK9 inhibition and statin therapy. Circulation 2018; 138(2): 141–149. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034645>.

  20. Lane T, Wassef N, Poole S et al. Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers. Circ Res 2014; 114(4): 672–676. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCRESAHA.114.302770>.

  21. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117(14): 3720–3732. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2010–07–273417>.

  22. Loppnow H, Libby P. Adult human vascular endothelial cells express the IL-6 gene differentially in response to LPS or IL-1. Cell Immunol 1989; 122(2): 493–503.

  23. Ridker PM, Howard CP, Walter V et al. Effects of interleukin-1 beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation 2012; 126(23): 2739–2748. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.112.122556>.

  24. Everett BM, Donath MY, Pradhan A et al. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. J Am Coll Cardiol 2018; 71(21): 2392–2401. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2018.03.002>.

  25. Ridker PM, MacFadyen JG, Glynn RJ et al. Inhibition of interlelukin 1ß by canakinumab and cardiovascular outcomes in patients with chronic kidney disease. J Am Coll Cardiol 2018; 71(21): 2405–2414. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2018.03.490>.

  26. Ridker PM, MacFadyen JG, Everett BM et al. [CANTOS Trial Group]. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomized controlled trial. Lancet 2018; 391(10118): 319–328. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(17)32814–3>.

  27. Ridker PM, MacFadyen JG, Thuren T et al. [CANTOS Trial Group]. Effect of interleukin-1ß inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomized, double-blind, placebo-controled trial. Lancet 2017; 390(10105): 1833–1842. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(17)32247-X>.

  28. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917): 860–867. Dostupné z DOI: <http://dx.doi.org/10.1038/nature01322>.

  29. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6): 883–899. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cell.2010.01.025>.

  30. Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev 2010; 29(2): 317–329. Dostupné z DOI: <http://dx.doi.org/10.1007/s10555–010–9229–0>.

  31. Morton AC, Rothman AM, Greenwood JP et al. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart study. Eur Heart J 2015; 36(6): 377–384. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu272>.

  32. Kleveland O, Kunszt G,l Bratlie M et al. Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial. Eur Heart J 2016; 37(30): 2406–2413. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw171>.

  33. Abbate A, Van Tassell BW, Biondi-Zoccai G et al. Effects of interleuki-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction (from the Virginia Commonwealth University-anakinra remodeling trial 2 [VCU-ART2] pilot study). Am J Cardiol 2013; 111(10): 1394–1400. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2013.01.287>.

  34. Everett BM, Pradhan AD, Solomon DH et al. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J 2013; 166(2): 199–207. e15. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ahj.2013.03.018>.

  35. van Hout GP, Bosch L, Ellenbroek GH et al. The selective NLRP3-inflammasome inhibitor mcc950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur Heart J 2017; 38(11): 828–836. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw247>.

  36. Nidorf SM, Eikelboom JW, Budgeon CA et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Col Cardiol 2013; 61(4): 404–410. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2012.10.027>.

  37. Baylis RA, Gomez D, Mallat Z et al. The CANTOS trial. One important step for clinical cardiology but a giant leap for vascular biology. Arterioscler Thromb Vasc Biol 2017; 37(11): e174-e177. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.117.310097>.

  38. Hansson GK. Inflammation and atherosclerosis. The end of a controversy. Circulation 2017; 136(20): 1875–1877. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030484>.

  39. 39. Weber C, von Hundelshausen P. CANTOS trial validates the inflammatory pathogenesis of atherosclerosis. Circ Res 2017; 121(10): 1119–1121. Dostupné z DOI: <http>//doi: 10.1161/CIRCRESAHA.117.311984>.

Labels
Diabetology Obesitology
Familial hypercholesterolemia and project MedPed FH
DNA diagnostics of the most common forms of monogenic diabetes in Slovakia
Hypoglycaemia in diabetes mellitus
New technologies in diabetology of continuous monitoring – new options in the treatment of diabetes mellitus
A way from EBM to the latest consensus report by the ADA and EASD: management of hyperglycaemia in T2DM, 2018
Metformin in patients with chronic kidney disease and cardiovascular disease
50 rokov Slovenskej diabetologickej spoločnosti
Odišiel MUDr. Peter Pavlov, MPH (*8. 6. 1962 – †19. 4. 2019)
Article was published in

Diabetes a obezita

Issue 37
2019 Issue 37
Most read in this issue
Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#