nach oben

Current Atherosclerosis Reports

Erschienen in:

01.12.2021 | Statin Drugs (R. Ceska, Section Editor)

Statins and Inflammation

verfasst von: Martin Satny, Jaroslav A. Hubacek, Michal Vrablik

Erschienen in: Current Atherosclerosis Reports | Ausgabe 12/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms’ initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings.

Recent Findings

Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively. Clinical trial with selective inhibitor of a principal inflammatory mediator interleukin 1-beta — canakinumab — confirmed the notion of direct vasculoprotective effects of primarily targeting inflammation. This has increased interest in the non-lipid, pleiotropic and, particularly, anti-inflammatory effects of statins.

Summary

Anti-inflammatory effects of statins have been proven both experimentally and in clinical settings beyond any doubt. They comprise a direct positive effect on not only many cell types and pathways that are lipid independent but, also, some that are mediated by lipid modification. Undoubtedly, suppression of inflammatory response by statins contributes to their generally positive action in atherosclerosis and represents an important part of the vasculo- and atheroprotective effect of this drug class.

Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study, 2004. 364(9438), 937–952. https://doi.org/10.1016/S0140-6736(04)17018-9.

Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal, 2020. 41(1) 111–188.

•• Montecucco F, Liberale L, Bonaventura A, et al. The role of inflammation in cardiovascular outcome. Curr Atheroscler. 2017. Rep. 9(3)11. A comprehensive review focusing on and summarizing the roles of innate immunity in the vascular inflammation initiation and propagation and its role in cardiovascular events risk.

Chatzizisis Y, CoskunA, Jonas M, et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol. 2007;49:2379–93.

•• Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–1696. A landmark paper summarizing the inflammatory aspects of atherosclerosis and involvement of different cellular and chemical species in different stages of atherogenesis.

•• 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. A narrative review focused on a central inflammatory mediator – interleukin-1 beta including illustrations of translation of basic research findings in clinical applications.

Montecucco F, Mach F. Update on statin-mediated anti-inflammatory activities in atherosclerosis. Semin Immunopathol. 2009;31(1):127–42. https://doi.org/10.1007/s00281-009-0150-y.CrossRefPubMed

Zwaal RF, Comfurius P, Bevers EM. Surface exposure of phosphatidylserine in pathological cells. Cellular Mol Life Sci CMLS. 2005;62(9):971–88. https://doi.org/10.1007/s00018-005-4527-3.CrossRefPubMed

Schiro A, Wilkinson F, Weston R, et al. Endothelial microparticles as conveyors of information in atherosclerotic disease. Atherosclerosis. 2014;234:295–302.CrossRef

10.

Hulsmans M, De Keyzer D, Holvoet P. MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J. 2011;25(8):2515–27. https://doi.org/10.1096/fj.11-181149.CrossRefPubMed

11.

Chen LJ, Lim SH, Yeh YT, et al. Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci. 2012;19(1):79. https://doi.org/10.1186/1423-0127-19-79.CrossRefPubMedPubMedCentral

12.

Fatkhullina AR, Peshkova IO, Koltsova EK. The role of cytokines in the development of atherosclerosis. Biochemistry (Moscow). 2016, 81(11), 1358–1370. https://doi.org/10.1134/S0006297916110134.

13.

Golia E, Limongelli G, Natale F, et al. Inflammation and cardiovascular disease: from pathogenesis to therapeutic target. Curr Atheroscler Rep. 2014, 16(9). https://doi.org/10.1007/s11883-014-0435-z

14.

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):973–9. https://doi.org/10.1056/NEJM199704033361401.CrossRefPubMed

15.

Calabro’ P, Golia E, Yeh ET. CRP and the risk of atherosclerotic events. Semin Immunopathol. 2009;31(1):79–94. https://doi.org/10.1007/s00281-009-0149-4.CrossRef

16.

Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Pennells L, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367(14):1310–20. https://doi.org/10.1056/NEJMoa1107477.

17.

•• Tabrizi R, Tamtaji OR, Mirhosseini N, et al. The effects of statin use on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;141:85–103. https://doi.org/10.1016/j.phrs.2018.12.010. A large metaanalysis following potentially beneficial action of statins in reducing inflammatory response in patients with metabolic syndrome with particular emphasis on the risk-benefit ratio of new onset diabetes in this population.

18.

Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101(15)1767–1772. https://doi.org/10.1161/01.CIR.101.15.1767.

19.

Cesari M, Penninx BWJH, Newman AB, et al. Inflammatory markers and onset of cardiovascular events. Circulation. 2003, 108(19), 2317–2322. https://doi.org/10.1161/01.CIR.0000097109.90783.FC.

20.

Weber C, Schober A, Zernecke A. Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease. Arterioscler Thromb Vasc Biol. 2004;24:1997–2008.CrossRef

21.

Niki T, Soeki T, Yamaguchi K, et al. Elevated concentration of interferon-inducible protein of 10 kD (IP-10) is associated with coronary atherosclerosis. Int Heart J. 2015;56:269–72.CrossRef

22.

Soeki T, Sata M. Inflammatory biomarkers and atherosclerosis. Int Heart J. 2016;57(2)134–139. https://doi.org/10.1536/ihj.15-346.

23.

Matsuo Y, Kubo T, Okumoto Y, et al. Circulating malondialdehyde-modified low-density lipoprotein levels are associated with the presence of thin-cap fibroatheromas determined by optical coherence tomography in coronary artery disease. Eur Heart J Cardiovasc Imaging. 2013;14:43–50.CrossRef

24.

• Chiurchiu V, Leuti A, Maccarrone M. Bioactive lipids and chronic inflammation: managing the fire within. Front Immunol. 2018;9, 38. https://doi.org/10.3389/fimmu.2018.00038. Explanation of how different lipid species interact with inflammatory pathways important for initiation and progression of vascular wall inflammation and many other chronic inflammatory conditions.

25.

Tousoulis D, Psarros C, Demosthenous M, et al. Innate and adaptive inflammation as a therapeutic target in vascular disease: the emerging role of statins. J Am Coll Cardiol. 2014;63(23):2491–502. https://doi.org/10.1016/j.jacc.2014.01.054.CrossRefPubMed

26.

•• Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12)1119–1131. https://doi.org/10.1056/NEJMoa1707914. A landmark clinical trial demonstrating for the first time an intervention targeting inflammation without impacting any other atherosclerosis risk factor is effective in reducing the risk of cardiovascular events.

27.

Ridker PM, Everett BM, Pradhan A, et al. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019;380(8), 752–762. https://doi.org/10.1056/NEJMoa1809798.

28.

Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020, 383(19), 1838–1847. https://doi.org/10.1056/NEJMoa2021372.

29.

Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019, 381(26), 2497–2505. https://doi.org/10.1056/NEJMoa1912388.

30.

• Liberale L, Carbone F, Montecucco F et al. Statins reduce vascular inflammation in atherogenesis: a review of underlying molecular mechanisms. Int J Biochem Cell Biol. 2020, 122. https://doi.org/10.1016/j.biocel.2020.105735. A review summarizing potential mechanisms important for the anti-inflammatory action of statins.

31.

Dimitrova Y, Dunoyer-Geindre S, Reber G, et al. Effects of statins on adhesion molecule expression in endothelial cells. J Thrombaemost. 2003;1:2290–9.CrossRef

32.

Obama R, Ishida H, Takizawa S, et al. Direct inhibition by a statin of TNFα-induced leukocyte recruitment in rat pial venules: in vivo confocal microscopic study. Pathophysiology. 2004;11:121–8.CrossRef

33.

Diomede L, Albani D, Donati MB, et al. In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. Arterioscler Thromb Vasc Biol. 2001;21:1327–32.CrossRef

34.

Greenwood J, Mason JC. Statins and the vascular endothelial inflammatory response. Trends Immunol. 2007;28(2):88–98. https://doi.org/10.1016/j.it.2006.12.003.CrossRefPubMed

35.

Laufs U, La Fata V, Plutzky J, et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.CrossRef

36.

Pannu R, Barbosa E, Singh AK, et al. Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res. 2005;79:340–50.CrossRef

37.

Wassmann S, Laufs U, Muller K, et al. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2002;22:300–5.CrossRef

38.

Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959–65. https://doi.org/10.1056/NEJM200106283442601.CrossRefPubMed

39.

Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352(1):20–8. https://doi.org/10.1056/NEJMoa042378.CrossRefPubMed

40.

Albert MA, Danielson E, Rifai N, et al. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;286(1):64–70.CrossRef

41.

•• Ridker PM, Danielson E, Fonseca FA et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207. https://doi.org/10.1056/NEJMoa0807646. Landmark clinical trial demonstrating the utility of inflammatory markers in stratification of cardiovascular risk and determining the benefit of statin therapy.

42.

Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.CrossRef

43.

Puri R, Nissen SE, Libby P, et al. C-reactive protein, but not low-density lipoprotein cholesterol levels, associate with coronary atheroma regression and cardiovascular events after maximally intensive statin therapy. Circulation. 2013;128:2395–403.CrossRef

44.

Hong YJ, Jeong MH, Ahn Y, et al. Effect of pitavastatin treatment on changes of plaque volume and composition according to the reduction of high-sensitivity C-reactive protein levels. J Cardiol. 2012;60:277–82.CrossRef

45.

Noguchi T, Tanaka A, Kawasaki T, et al. Effect of intensive statin therapy on coronary high-intensity plaques detected by noncontrast T1-weighted imaging. The AQUAMARINE Pilot Study. J Am Coll Cardiol. 2015;66:245–56.

46.

Komukai K, Kubo T, Kitabata H, et al. Effect of atorvastatin on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography. The EASYFIT Study. J Am Coll Cardiol. 2014;64:2207–17.

47.

Waters D, Schwartz GG, Olsson AG. The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial: a new frontier for statins? Current controlled trials in cardiovascular medicine. 2001. 2(3). https://doi.org/10.1186/CVM-2-3-111.

Titel: Statins and Inflammation
verfasst von: Martin Satny
Jaroslav A. Hubacek
Michal Vrablik
Publikationsdatum: 01.12.2021
Verlag: Springer US
Erschienen in: Current Atherosclerosis Reports / Ausgabe 12/2021
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-021-00977-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Statins and Inflammation

Abstract

Purpose of Review

Recent Findings

Summary

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2021

Moving the Needle on Atherosclerotic Cardiovascular Disease and Heart Failure with Influenza Vaccination

Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

Differences in the 2020 ESC Versus 2015 ESC and 2014 ACC/AHA Guidelines on the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-Segment Elevation

Watermelon and l-Citrulline in Cardio-Metabolic Health: Review of the Evidence 2000–2020

Gene-Environment Interactions for Cardiovascular Disease

Oral Lipid-Lowering Treatments Beyond Statins: Too Old and Outdated or Still Useful?

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin