Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

High Sensitivity C-reactive Protein (hsCRP) and its Implications in Cardiovascular Outcomes

Author(s): Andrea Denegri and Giuseppe Boriani*

Volume 27, Issue 2, 2021

Published on: 17 July, 2020

Page: [263 - 275] Pages: 13

DOI: 10.2174/1381612826666200717090334

Price: $65

Abstract

Atherosclerosis and its fearsome complications represent the first cause of morbidity and mortality worldwide. Over the last two decades, several pieces of evidence have been accumulated, suggesting a central role of inflammation in atheroma development. High sensitivity C-reactive protein (hsCRP) is a well-established marker of cardiovascular (CV) disease; high levels of hsCRP have been associated with adverse CV outcome after acute coronary syndrome (ACS) and, despite some controversy, an active role for hsCRP in initiation and development of the atherosclerotic plaque has been also proposed. Randomized clinical trials focusing on hsCRP have been crucial in elucidating the anti-inflammatory effects of statin therapy. Thus, hsCRP has been progressively considered a real CV risk factor likewise to low-density lipoprotein cholesterol (LDL-C), expanding the concept of residual CV inflammatory risk. Subsequent research has been designed to investigate potential new targets of atherothrombotic protection. Despite the fact that the clinical usefulness of hsCRP is widely recognized, hsCRP may not represent the ideal target of specific anti-inflammatory therapies. Clinical investigations, therefore, have also focused on other inflammatory mediators, restricting hsCRP to an indicator rather than a therapeutic target. The aim of the present review is to provide an illustrative overview of the current knowledge of atherosclerosis and inflammation, highlighting the most representative clinical studies of lipid-lowering and antiinflammatory therapies focused on hsCRP in CV diseases.

Keywords: Atherosclerosis, inflammation, hsCRP, lipid-lowering therapies, statins, cardiovascular disease, acute coronary syndrome.

« Previous Next »
[1]
Lüscher TF. Outcomes of acute coronary syndromes: clinical presentation, gender, inflammation, and cell therapy. Eur Heart J 2017; 38(3): 125-9.
[http://dx.doi.org/10.1093/eurheartj/ehw676] [PMID: 28158616]
[2]
Ridker PM, Everett BM, Thuren T, et al. CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017; 377(12): 1119-31.
[http://dx.doi.org/10.1056/NEJMoa1707914] [PMID: 28845751]
[3]
He LP, Tang XY, Ling WH, Chen WQ, Chen YM. Early C-reactive protein in the prediction of long-term outcomes after acute coronary syndromes: a meta-analysis of longitudinal studies. Heart 2010; 96(5): 339-46.
[http://dx.doi.org/10.1136/hrt.2009.174912] [PMID: 20197361]
[4]
Ridker PM. Clinician’s guide to reducing inflammation to reduce atherothrombotic risk: JACC review topic of the week. J Am Coll Cardiol 2018; 72(25): 3320-31.
[http://dx.doi.org/10.1016/j.jacc.2018.06.082] [PMID: 30415883]
[5]
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336(14): 973-9.
[http://dx.doi.org/10.1056/NEJM199704033361401] [PMID: 9077376]
[6]
Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98(8): 731-3.
[http://dx.doi.org/10.1161/01.CIR.98.8.731] [PMID: 9727541]
[7]
Rymer JA, Newby LK. Failure to Launch: Targeting Inflammation in Acute Coronary Syndromes. JACC Basic Transl Sci 2017; 2(4): 484-97.
[http://dx.doi.org/10.1016/j.jacbts.2017.07.001] [PMID: 30062164]
[8]
Kaptoge S, Di Angelantonio E, Lowe G, et al. Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375(9709): 132-40.
[http://dx.doi.org/10.1016/S0140-6736(09)61717-7] [PMID: 20031199]
[9]
Piepoli MF, Hoes AW, Agewall S, et al. ESC Scientific Document Group 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016; 37(29): 2315-81.
[http://dx.doi.org/10.1093/eurheartj/ehw106] [PMID: 27222591]
[10]
Penson PE, Long DL, Howard G, et al. Associations between very low concentrations of low density lipoprotein cholesterol, high sensitivity C-reactive protein, and health outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study. Eur Heart J 2018; 39(40): 3641-53.
[http://dx.doi.org/10.1093/eurheartj/ehy533] [PMID: 30165636]
[11]
Virchow RLK. Cellular Pathology. London: John Churchill 1860.
[12]
Ridker PM, Koenig W, Kastelein JJ, Mach F, Lüscher TF. Has the time finally come to measure hsCRP universally in primary and secondary cardiovascular prevention? Eur Heart J 2018; 39(46): 4109-11.
[http://dx.doi.org/10.1093/eurheartj/ehy723] [PMID: 30452612]
[13]
Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004; 350(14): 1387-97.
[http://dx.doi.org/10.1056/NEJMoa032804] [PMID: 15070788]
[14]
Alber DG, Powell KL, Vallance P, Goodwin DA, Grahame-Clarke C. Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse. Circulation 2000; 102(7): 779-85.
[http://dx.doi.org/10.1161/01.CIR.102.7.779] [PMID: 10942747]
[15]
Grau AJ, Boddy AW, Dukovic DA, et al. CAPRIE Investigators Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004; 35(5): 1147-52.
[http://dx.doi.org/10.1161/01.STR.0000124122.71702.64] [PMID: 15017013]
[16]
Mattila KJ. Viral and bacterial infections in patients with acute myocardial infarction. J Intern Med 1989; 225(5): 293-6.
[http://dx.doi.org/10.1111/j.1365-2796.1989.tb00084.x] [PMID: 2732669]
[17]
Valtonen V, Kuikka A, Syrjanen J. Thromboembolic complications in bacteraemic infections. Eur Heart J 1993; 14: 20-3.
[18]
Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004; 351(25): 2611-8.
[http://dx.doi.org/10.1056/NEJMoa041747] [PMID: 15602021]
[19]
Zhu J, Nieto FJ, Horne BD, Anderson JL, Muhlestein JB, Epstein SE. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation 2001; 103(1): 45-51.
[http://dx.doi.org/10.1161/01.CIR.103.1.45] [PMID: 11136684]
[20]
Maniar A, Ellis C, Asmuth D, Pollard R, Rutledge J. HIV infection and atherosclerosis: evaluating the drivers of inflammation. Eur J Prev Cardiol 2013; 20(5): 720-8.
[http://dx.doi.org/10.1177/2047487312447843] [PMID: 22556374]
[21]
Dratva J, Caviezel S, Schaffner E, et al. Infectious diseases are associated with carotid intima media thickness in adolescence. Atherosclerosis 2015; 243(2): 609-15.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.021] [PMID: 26545015]
[22]
Burgner DP, Sabin MA, Magnussen CG, et al. Early childhood hospitalisation with infection and subclinical atherosclerosis in adulthood: the Cardiovascular Risk in Young Finns Study. Atherosclerosis 2015; 239(2): 496-502.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.024] [PMID: 25721701]
[23]
Burgner DP, Cooper MN, Moore HC, et al. Childhood hospitalisation with infection and cardiovascular disease in early-mid adulthood: a longitudinal population-based study. PLoS One 2015; 10(5)e0125342
[http://dx.doi.org/10.1371/journal.pone.0125342] [PMID: 25938548]
[24]
Qanitha A, de Mol BA, Pabittei DR, et al. Infections in early life and premature acute coronary syndrome: A case-control study. Eur J Prev Cardiol 2016; 23(15): 1640-8.
[http://dx.doi.org/10.1177/2047487316640656] [PMID: 27006417]
[25]
Rosenfeld ME, Campbell LA. Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost 2011; 106(5): 858-67.
[PMID: 22012133]
[26]
Liuba P, Pesonen E. Infection and early atherosclerosis: does the evidence support causation? Acta Paediatr 2005; 94(6): 643-51.
[http://dx.doi.org/10.1111/j.1651-2227.2005.tb01958.x] [PMID: 16188762]
[27]
Pessi T, Karhunen V, Karjalainen PP, et al. Bacterial signatures in thrombus aspirates of patients with myocardial infarction Circulation 2013; 127(11): 1219-28. e1-e6
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.001254] [PMID: 23418311]
[28]
Ott SJ, El Mokhtari NE, Musfeldt M, et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation 2006; 113(7): 929-37.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.579979] [PMID: 16490835]
[29]
Liuba P, Persson J, Luoma J, Ylä-Herttuala S, Pesonen E. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. Eur Heart J 2003; 24(6): 515-21.
[http://dx.doi.org/10.1016/S0195-668X(02)00750-9] [PMID: 12643884]
[30]
Lüscher TF. Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. Eur Heart J 1989; 10(9): 847-57.
[http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a059580] [PMID: 2680493]
[31]
Mantel Ä, Holmqvist M, Jernberg T, Wållberg-Jonsson S, Askling J. Rheumatoid arthritis is associated with a more severe presentation of acute coronary syndrome and worse short-term outcome. Eur Heart J 2015; 36(48): 3413-22.
[http://dx.doi.org/10.1093/eurheartj/ehv461] [PMID: 26400826]
[32]
Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum 2013; 43(1): 77-95.
[http://dx.doi.org/10.1016/j.semarthrit.2012.12.002] [PMID: 23422269]
[33]
Gustafsson JT, Simard JF, Gunnarsson I, et al. Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study. Arthritis Res Ther 2012; 14(2): R46.
[http://dx.doi.org/10.1186/ar3759] [PMID: 22390680]
[34]
Pons-Estel GJ, González LA, Zhang J, et al. Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort. Rheumatology (Oxford) 2009; 48(7): 817-22.
[http://dx.doi.org/10.1093/rheumatology/kep102] [PMID: 19454606]
[35]
Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol 2015; 11(7): 390-400.
[http://dx.doi.org/10.1038/nrrheum.2015.40] [PMID: 25825281]
[36]
Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59(12): 1690-7.
[http://dx.doi.org/10.1002/art.24092] [PMID: 19035419]
[37]
Paparo F, Denegri A, Revelli M, et al. Crohn’s disease: value of diagnostic imaging in the evaluation of anastomotic recurrence. Ann Ital Chir 2014; 85(3): 271-81.
[PMID: 23474468]
[38]
Fornaro R, Frascio M, Stabilini C, et al. [Crohn’s disease surgery: problems of postoperative recurrence] Chir Ital 2008; 60(6): 761-81.
[PMID: 19256268]
[39]
Denegri A, Paparo F, Denegri R, et al. A multidisciplinary approach to short bowel syndrome. Ann Ital Chir 2014; 85(4): 332-40.
[PMID: 24393697]
[40]
Kwon JH. Disease Phenotype, Activity and Clinical Course Prediction Based on C-Reactive Protein Levels at Diagnosis in Patients with Crohn’s Disease: Results from the CONNECT Study. Gut Liver 2016; 10(4): 595-603.
[http://dx.doi.org/10.5009/gnl15411] [PMID: 27021506]
[41]
Wang A, Liu J, Li C, et al. Cumulative exposure to high-sensitivity C-Reactive protein predicts the risk of cardiovascular disease. J Am Heart Assoc 2017; 6(10)e005610
[http://dx.doi.org/10.1161/JAHA.117.005610] [PMID: 29066453]
[42]
Weiner SD, Ahmed HN, Jin Z, et al. Systemic inflammation and brachial artery endothelial function in the Multi-Ethnic Study of Atherosclerosis (MESA). Heart 2014; 100(11): 862-6.
[http://dx.doi.org/10.1136/heartjnl-2013-304893] [PMID: 24714919]
[43]
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352(16): 1685-95.
[http://dx.doi.org/10.1056/NEJMra043430] [PMID: 15843671]
[44]
Panhwar MS, Mansoor E, Al-Kindi SG, et al. Risk of myocardial infarction in inflammatory bowel disease: a population-based national study. Inflamm Bowel Dis 2019; 25(6): 1080-7.
[http://dx.doi.org/10.1093/ibd/izy354] [PMID: 30500938]
[45]
Feng W, Chen G, Cai D, Zhao S, Cheng J, Shen H. Inflammatory bowel disease and risk of ischemic heart disease: an updated meta-analysis of cohort studies. J Am Heart Assoc 2017; 6(8)e005892
[http://dx.doi.org/10.1161/JAHA.117.005892] [PMID: 28768646]
[46]
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917): 860-7.
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959]
[47]
Aboumsallem JP, Moslehi J, de Boer RA. Reverse Cardio-Oncology: Cancer Development in Patients With Cardiovascular Disease. J Am Heart Assoc 2020; 9(2)e013754
[http://dx.doi.org/10.1161/JAHA.119.013754] [PMID: 31960736]
[48]
de Boer RA, Meijers WC, van der Meer P, van Veldhuisen DJ. Cancer and heart disease: associations and relations. Eur J Heart Fail 2019; 21(12): 1515-25.
[http://dx.doi.org/10.1002/ejhf.1539] [PMID: 31321851]
[49]
Libby P, Kobold S. Inflammation: a common contributor to cancer, aging, and cardiovascular diseases-expanding the concept of cardio-oncology. Cardiovasc Res 2019; 115(5): 824-9.
[http://dx.doi.org/10.1093/cvr/cvz058] [PMID: 30830168]
[50]
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-87.
[http://dx.doi.org/10.1016/j.ejca.2018.07.005] [PMID: 30100160]
[51]
White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation-therapeutic opportunities and pharmacological challenges. Pharmacol Rev 2013; 65(1): 47-89.
[http://dx.doi.org/10.1124/pr.111.005074] [PMID: 23300131]
[52]
Herrmann J. Vascular toxic effects of cancer therapies. Nat Rev Cardiol 2020; 1-20.
[http://dx.doi.org/10.1038/s41569-020-0347-2]
[53]
Mukai M, Komori K, Oka T. Mechanism and Management of Cancer Chemotherapy-Induced Atherosclerosis. J Atheroscler Thromb 2018; 25(10): 994-1002.
[http://dx.doi.org/10.5551/jat.RV17027] [PMID: 30224607]
[54]
Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-45.
[http://dx.doi.org/10.1146/annurev-immunol-031210-101322] [PMID: 21219177]
[55]
Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 2006; 55(6): 1537-45.
[http://dx.doi.org/10.2337/db06-0263] [PMID: 16731815]
[56]
Lüscher TF. Novel insights into body fat distribution and cardiometabolic risk. Eur Heart J 2019; 40(34): 2833-6.
[http://dx.doi.org/10.1093/eurheartj/ehz634] [PMID: 31539907]
[57]
Marques-Vidal P, Bochud M, Bastardot F, et al. Association between inflammatory and obesity markers in a Swiss population-based sample (CoLaus Study). Obes Facts 2012; 5(5): 734-44.
[http://dx.doi.org/10.1159/000345045] [PMID: 23108472]
[58]
Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol 2004; 43(10): 1731-7.
[http://dx.doi.org/10.1016/j.jacc.2003.12.047] [PMID: 15145091]
[59]
Morris PB, Ference BA, Jahangir E, et al. Cardiovascular effects of exposure to cigarette smoke and electronic cigarettes: clinical perspectives from the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology. J Am Coll Cardiol 2015; 66(12): 1378-91.
[http://dx.doi.org/10.1016/j.jacc.2015.07.037] [PMID: 26383726]
[60]
Siasos G, Tsigkou V, Kokkou E, et al. Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches. Curr Med Chem 2014; 21(34): 3936-48.
[http://dx.doi.org/10.2174/092986732134141015161539] [PMID: 25174928]
[61]
Kianoush S, Yakoob MY, Al-Rifai M, et al. Associations of Cigarette Smoking With Subclinical Inflammation and Atherosclerosis: ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health). J Am Heart Assoc 2017; 6(6)e005088
[http://dx.doi.org/10.1161/JAHA.116.005088] [PMID: 28647689]
[62]
Lazo M, Chen Y, McEvoy JW, et al. Alcohol consumption and cardiac biomarkers: The Atherosclerosis Risk in Communities (ARIC) Study. Clin Chem 2016; 62(9): 1202-10.
[http://dx.doi.org/10.1373/clinchem.2016.255778] [PMID: 27440513]
[63]
Shaper AG, Wannamethee SG. Alcohol intake and mortality in middle aged men with diagnosed coronary heart disease. Heart 2000; 83(4): 394-9.
[http://dx.doi.org/10.1136/heart.83.4.394] [PMID: 10722536]
[64]
Chevli PA, Aladin AI, Kanaya AM, Kandula NR, Malaver D, Herrington DM. Alcohol consumption and subclinical atherosclerosis among South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Nutr Metab Cardiovasc Dis 2020; 30(1): 123-31.
[http://dx.doi.org/10.1016/j.numecd.2019.07.021] [PMID: 31753783]
[65]
Averina M, Nilssen O, Arkhipovsky VL, Kalinin AG, Brox J. C-reactive protein and alcohol consumption: Is there a U-shaped association? Results from a population-based study in Russia. The Arkhangelsk study. Atherosclerosis 2006; 188(2): 309-15.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.11.007] [PMID: 16386256]
[66]
Iakunchykova O, Averina M, Kudryavtsev AV, et al. Evidence for a Direct Harmful Effect of Alcohol on Myocardial Health: A Large Cross-Sectional Study of Consumption Patterns and Cardiovascular Disease Risk Biomarkers From Northwest Russia, 2015 to 2017. J Am Heart Assoc 2020; 9(1)e014491
[http://dx.doi.org/10.1161/JAHA.119.014491] [PMID: 31847661]
[67]
Lawal AO. Air particulate matter induced oxidative stress and inflammation in cardiovascular disease and atherosclerosis: The role of Nrf2 and AhR-mediated pathways. Toxicol Lett 2017; 270: 88-95.
[http://dx.doi.org/10.1016/j.toxlet.2017.01.017] [PMID: 28189649]
[68]
Sjögren P, Cederholm T, Heimbürger M, et al. Simple advice on lifestyle habits and long-term changes in biomarkers of inflammation and vascular adhesion in healthy middle-aged men. Eur J Clin Nutr 2010; 64(12): 1450-6.
[http://dx.doi.org/10.1038/ejcn.2010.182] [PMID: 20859301]
[69]
Elhakeem A, Murray ET, Cooper R, Kuh D, Whincup P, Hardy R. Leisure-time physical activity across adulthood and biomarkers of cardiovascular disease at age 60-64: A prospective cohort study. Atherosclerosis 2018; 269: 279-87.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.11.019] [PMID: 29180005]
[70]
Denegri A, Rossi VA, Vaghi F, et al. A patient-centered multidisciplinary cardiac rehabilitation program improves glycemic control and functional outcome in coronary artery disease after percutaneous and surgical revascularization. Cardiol J 2020. In press
[http://dx.doi.org/10.5603/CJ.a2020.0006] [PMID: 32037504]
[71]
Flynn MG, McFarlin BK, Markofski MM. The Anti-Inflammatory Actions of Exercise Training. Am J Lifestyle Med 2007; 1(3): 220-35.
[http://dx.doi.org/10.1177/1559827607300283] [PMID: 25431545]
[72]
Hamer M, Sabia S, Batty GD, et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation 2012; 126(8): 928-33.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.103879] [PMID: 22891048]
[73]
Wick G, Perschinka H, Xu Q. Autoimmunity and atherosclerosis. Am Heart J 1999; 138(5 Pt. 2): S444-9.
[http://dx.doi.org/10.1016/S0002-8703(99)70272-3] [PMID: 10539845]
[74]
Wick G. Atherosclerosis-an autoimmune disease due to an immune reaction against heat-shock protein 60. Herz 2000; 25(2): 87-90.
[http://dx.doi.org/10.1007/PL00001957] [PMID: 10829245]
[75]
Tuttolomondo A, Di Raimondo D, Pecoraro R, Arnao V, Pinto A, Licata G. Atherosclerosis as an inflammatory disease. Curr Pharm Des 2012; 18(28): 4266-88.
[http://dx.doi.org/10.2174/138161212802481237] [PMID: 22390643]
[76]
Poupel L, Combadière C. [Atherosclerosis : on the trail of chemokines] Biol Aujourdhui 2010; 204(4): 285-93.
[http://dx.doi.org/10.1051/jbio/2010026] [PMID: 21215245]
[77]
Mach F. The role of chemokines in atherosclerosis. Curr Atheroscler Rep 2001; 3(3): 243-51.
[http://dx.doi.org/10.1007/s11883-001-0067-y] [PMID: 11286646]
[78]
van de Stolpe A, van der Saag PT. Intercellular adhesion molecule-1. J Mol Med (Berl) 1996; 74(1): 13-33.
[http://dx.doi.org/10.1007/BF00202069] [PMID: 8834767]
[79]
Kircher MF, Grimm J, Swirski FK, et al. Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions. Circulation 2008; 117(3): 388-95.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.719765] [PMID: 18172031]
[80]
Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol 2008; 8(10): 802-15.
[http://dx.doi.org/10.1038/nri2415] [PMID: 18825131]
[81]
Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis. Amn Heart Assoc Circulation 1995; 92(5): 1355-74.
[http://dx.doi.org/10.1161/01.CIR.92.5.1355] [PMID: 7648691]
[82]
Poredos P, Spirkoska A, Lezaic L, Mijovski MB, Jezovnik MK. Patients with an Inflamed Atherosclerotic Plaque have Increased Levels of Circulating Inflammatory Markers. J Atheroscler Thromb 2017; 24(1): 39-46.
[http://dx.doi.org/10.5551/jat.34884] [PMID: 27237221]
[83]
Calabró P, Willerson JT, Yeh ET. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation 2003; 108(16): 1930-2.
[http://dx.doi.org/10.1161/01.CIR.0000096055.62724.C5] [PMID: 14530191]
[84]
Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol 2001; 158(3): 1039-51.
[http://dx.doi.org/10.1016/S0002-9440(10)64051-5] [PMID: 11238052]
[85]
Kushner I, Broder ML, Karp D. Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest 1978; 61(2): 235-42.
[http://dx.doi.org/10.1172/JCI108932] [PMID: 621273]
[86]
Libby P. Inflammation in atherosclerosis. Nature 2002; 420(6917): 868-74.
[http://dx.doi.org/10.1038/nature01323] [PMID: 12490960]
[87]
Libby P, Nahrendorf M, Pittet MJ, Swirski FK. Diversity of denizens of the atherosclerotic plaque: not all monocytes are created equal. Circulation 2008; 117(25): 3168-70.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.783068] [PMID: 18574058]
[88]
Kones R. Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. A comprehensive survey. Drug Des Devel Ther 2011; 5: 325-80.
[http://dx.doi.org/10.2147/DDDT.S14934] [PMID: 21792295]
[89]
Jialal I, Verma S, Devaraj S. Inhibition of endothelial nitric oxide synthase by C-reactive protein: clinical relevance. Clin Chem 2009; 55(2): 206-8.
[http://dx.doi.org/10.1373/clinchem.2008.119206] [PMID: 19095724]
[90]
Eisenhardt SU, Habersberger J, Murphy A, et al. Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques. Circ Res 2009; 105(2): 128-37.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.190611] [PMID: 19520972]
[91]
Verma S, Devaraj S, Jialal I. Is C-reactive protein an innocent bystander or proatherogenic culprit? C-reactive protein promotes atherothrombosis. Circulation 2006; 113(17): 2135-50.
[PMID: 16671184]
[92]
Pepys MB, Hawkins PN, Kahan MC, et al. Proinflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products, not by C-reactive protein itself. Circ Res 2005; 97(11): e97-e103.
[http://dx.doi.org/10.1161/01.RES.0000193595.03608.08] [PMID: 16254214]
[93]
Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331(7): 417-24.
[http://dx.doi.org/10.1056/NEJM199408183310701] [PMID: 7880233]
[94]
Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349(9050): 462-6.
[http://dx.doi.org/10.1016/S0140-6736(96)07591-5] [PMID: 9040576]
[95]
de Winter RJ, Heyde GS, Koch KT, et al. The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty. Eur Heart J 2002; 23(12): 960-6.
[http://dx.doi.org/10.1053/euhj.2001.2988] [PMID: 12069451]
[96]
Chew DP, Bhatt DL, Robbins MA, et al. Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation 2001; 104(9): 992-7.
[http://dx.doi.org/10.1161/hc3401.095074] [PMID: 11524391]
[97]
Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. Circulation 1997; 96(12): 4204-10.
[http://dx.doi.org/10.1161/01.CIR.96.12.4204] [PMID: 9416883]
[98]
Milazzo D, Biasucci LM, Luciani N, et al. Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events. Am J Cardiol 1999; 84(4): 459-61.
[http://dx.doi.org/10.1016/S0002-9149(99)00333-1] [PMID: 10468087]
[99]
Ridker PM. High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. Am J Cardiol 2003; 92(4B): 17K-22K.
[http://dx.doi.org/10.1016/S0002-9149(03)00774-4] [PMID: 12948872]
[100]
Ray KK, Cannon CP, Cairns R, Morrow DA, Ridker PM, Braunwald E. Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol 2009; 29(3): 424-30.
[http://dx.doi.org/10.1161/ATVBAHA.108.181735] [PMID: 19122170]
[101]
Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347(20): 1557-65.
[http://dx.doi.org/10.1056/NEJMoa021993] [PMID: 12432042]
[102]
Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 2004; 109(16): 1955-9.
[http://dx.doi.org/10.1161/01.CIR.0000125690.80303.A8] [PMID: 15051634]
[103]
Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation 2004; 109(7): 837-42.
[http://dx.doi.org/10.1161/01.CIR.0000116763.91992.F1] [PMID: 14757686]
[104]
Koenig W, Sund M, Fröhlich M, et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99(2): 237-42.
[http://dx.doi.org/10.1161/01.CIR.99.2.237] [PMID: 9892589]
[105]
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. for the AFCAPS/TexCAPS Research Group. JAMA 1998; 279: 1615-22.
[http://dx.doi.org/10.1001/jama.279.20.1615] [PMID: 9613910]
[106]
Ridker PM, Rifai N, Clearfield M, et al. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators 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.
[http://dx.doi.org/10.1056/NEJM200106283442601] [PMID: 11430324]
[107]
Colhoun HM, Betteridge DJ, Durrington PN, et al. CARDS investigators Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364(9435): 685-96.
[http://dx.doi.org/10.1016/S0140-6736(04)16895-5] [PMID: 15325833]
[108]
Soedamah-Muthu SS, Livingstone SJ, Charlton-Menys V, et al. CARDS Investigators Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial. Diabetologia 2015; 58(7): 1494-502.
[http://dx.doi.org/10.1007/s00125-015-3586-8] [PMID: 25899452]
[109]
Ridker PM, Danielson E, Fonseca FA, et al. JUPITER Study Group Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359(21): 2195-207.
[http://dx.doi.org/10.1056/NEJMoa0807646] [PMID: 18997196]
[110]
The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344(8934): 1383-9.
[PMID: 7968073]
[111]
Crea F, Monaco C, Lanza GA, et al. Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study. Clin Cardiol 2002; 25(10): 461-6.
[http://dx.doi.org/10.1002/clc.4960251005] [PMID: 12375804]
[112]
Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335(14): 1001-9.
[http://dx.doi.org/10.1056/NEJM199610033351401] [PMID: 8801446]
[113]
Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339(19): 1349-57.
[http://dx.doi.org/10.1056/NEJM199811053391902] [PMID: 9841303]
[114]
Stewart RA, White HD, Kirby AC, et al. Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study Investigators White blood cell count predicts reduction in coronary heart disease mortality with pravastatin. Circulation 2005; 111(14): 1756-62.
[http://dx.doi.org/10.1161/01.CIR.0000160924.73417.26] [PMID: 15809366]
[115]
Shepherd J, Blauw GJ, Murphy MB, et al. PROSPER study group PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360(9346): 1623-30.
[http://dx.doi.org/10.1016/S0140-6736(02)11600-X] [PMID: 12457784]
[116]
Sattar N, Murray HM, Welsh P, et al. Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? PLoS Med 2009; 6(6)e1000099
[http://dx.doi.org/10.1371/journal.pmed.1000099] [PMID: 19554082]
[117]
Heart Protection Study Collaborative Group. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet 2011; 378(9808): 2013-20.
[http://dx.doi.org/10.1016/S0140-6736(11)61125-2] [PMID: 22115874]
[118]
Grundy SM, Cleeman JI, Merz CN, et al. National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110(2): 227-39.
[http://dx.doi.org/10.1161/01.CIR.0000133317.49796.0E] [PMID: 15249516]
[119]
Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 2007; 297(6): 611-9.
[http://dx.doi.org/10.1001/jama.297.6.611] [PMID: 17299196]
[120]
LaRosa JC, Grundy SM, Waters DD, et al. Treating to New Targets (TNT) Investigators Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352(14): 1425-35.
[http://dx.doi.org/10.1056/NEJMoa050461] [PMID: 15755765]
[121]
Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005; 294(19): 2437-45.
[http://dx.doi.org/10.1001/jama.294.19.2437] [PMID: 16287954]
[122]
Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285(13): 1711-8.
[http://dx.doi.org/10.1001/jama.285.13.1711] [PMID: 11277825]
[123]
Kinlay S, Schwartz GG, Olsson AG, et al. High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation 2003; 108(13): 1560-6.
[http://dx.doi.org/10.1161/01.CIR.0000091404.09558.AF] [PMID: 12975259]
[124]
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350(15): 1495-504.
[http://dx.doi.org/10.1056/NEJMoa040583] [PMID: 15007110]
[125]
Ridker PM, Morrow DA, Rose LM, Rifai N, Cannon CP, Braunwald E. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol 2005; 45(10): 1644-8.
[http://dx.doi.org/10.1016/j.jacc.2005.02.080] [PMID: 15893181]
[126]
Mega JL, Morrow DA, Cannon CP, et al. Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy. J Thromb Thrombolysis 2006; 22(1): 71-6.
[http://dx.doi.org/10.1007/s11239-006-8081-0] [PMID: 16786236]
[127]
Morrow DA, de Lemos JA, Sabatine MS, et al. Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation 2006; 114(4): 281-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.628909] [PMID: 16847150]
[128]
Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352(1): 29-38.
[http://dx.doi.org/10.1056/NEJMoa042000] [PMID: 15635110]
[129]
Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006; 295(13): 1556-65.
[http://dx.doi.org/10.1001/jama.295.13.jpc60002] [PMID: 16533939]
[130]
Nicholls SJ, Borgman M, Nissen SE, et al. Impact of statins on progression of atherosclerosis: rationale and design of SATURN (Study of Coronary Atheroma by InTravascular Ultrasound: effect of Rosuvastatin versus AtorvastatiN). Curr Med Res Opin 2011; 27(6): 1119-29.
[http://dx.doi.org/10.1185/03007995.2011.570746] [PMID: 21446892]
[131]
Ridker PM. How common is residual inflammatory risk? Circ Res 2017; 120(4): 617-9.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.310527] [PMID: 28209792]
[132]
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372(25): 2387-97.
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]
[133]
Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132(13): 1224-33.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018381] [PMID: 26330412]
[134]
Denegri A, Petrova-Slater I, Pasotti E, et al. PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy. J Cardiovasc Med (Hagerstown) 2016; 17(4): 237-44.
[http://dx.doi.org/10.2459/JCM.0000000000000360] [PMID: 26855411]
[135]
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[136]
Bohula EA, Giugliano RP, Leiter LA, et al. Inflammatory and Cholesterol Risk in the FOURIER Trial. Circulation 2018; 138(2): 131-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034032] [PMID: 29530884]
[137]
Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379(22): 2097-107.
[http://dx.doi.org/10.1056/NEJMoa1801174] [PMID: 30403574]
[138]
Pradhan AD, Aday AW, Rose LM, Ridker PM. Residual inflammatory risk on treatment with PCSK9 inhibition and statin therapy. Circulation 2018; 138(2): 141-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034645] [PMID: 29716940]
[139]
Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med 2017; 376(15): 1430-40.
[http://dx.doi.org/10.1056/NEJMoa1615758] [PMID: 28306389]
[140]
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140(11): e596-646.
[http://dx.doi.org/10.1161/CIR.0000000000000678] [PMID: 30879355]
[141]
Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 2007; 115(12): 1528-36.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.649939] [PMID: 17372173]
[142]
Held C, White HD, Stewart RAH, et al. Inflammatory biomarkers interleukin-6 and C-reactive protein and outcomes in stable coronary heart disease: experiences from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. J Am Heart Assoc 2017; 6(10)e005077
[http://dx.doi.org/10.1161/JAHA.116.005077] [PMID: 29066452]
[143]
Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. FRISC Study Group (Fragmin During Instability in Coronary Artery Disease). Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med 2000; 343: 1139-47.
[http://dx.doi.org/10.1056/NEJM200010193431602] [PMID: 11036119]
[144]
Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ. CANTOS Trial Group Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet 2018; 391(10118): 319-28.
[http://dx.doi.org/10.1016/S0140-6736(17)32814-3] [PMID: 29146124]
[145]
Ridker PM, Libby P, MacFadyen JG, et al. Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J 2018; 39(38): 3499-507.
[http://dx.doi.org/10.1093/eurheartj/ehy310] [PMID: 30165610]
[146]
Ridker PM, Everett BM, Pradhan A, et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med 2019; 380(8): 752-62.
[http://dx.doi.org/10.1056/NEJMoa1809798] [PMID: 30415610]
[147]
Ridker PM. Anti-inflammatory therapy for atherosclerosis: interpreting divergent results from the CANTOS and CIRT clinical trials. J Intern Med 2019; 285(5): 503-9.
[http://dx.doi.org/10.1111/joim.12862] [PMID: 30472762]
[148]
Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013; 61(4): 404-10.
[http://dx.doi.org/10.1016/j.jacc.2012.10.027] [PMID: 23265346]
[149]
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): 2497-505.
[http://dx.doi.org/10.1056/NEJMoa1912388] [PMID: 31733140]
[150]
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): 377-84.
[http://dx.doi.org/10.1093/eurheartj/ehu272] [PMID: 25079365]
[151]
Kleveland O, Kunszt G, 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): 2406-13.
[http://dx.doi.org/10.1093/eurheartj/ehw171] [PMID: 27161611]
[152]
Holte E, Kleveland O, Ueland T, et al. Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction. Heart 2017; 103(19): 1521-7.
[http://dx.doi.org/10.1136/heartjnl-2016-310875] [PMID: 28432157]
[153]
Rout A, Sukhi A, Chaudhary R, Bliden KP, Tantry US, Gurbel PA. Investigational drugs in phase II clinical trials for acute coronary syndromes. Expert Opin Investig Drugs 2020; 29(1): 33-47.
[http://dx.doi.org/10.1080/13543784.2020.1708324] [PMID: 31869253]

Rights & Permissions Print Cite
Article Metrics
40
1
© 2024 Bentham Science Publishers | Privacy Policy