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References 1. R. J. Herman, Drug interactions and the statins, CMAJ 161 (1999) 1281-1286. 2. Cardiovascular Drugs , in Martindale : The Complete Drug Reference , 36th ed. (Ed. S. C. Sweetman), Pharmaceutical Press, London 2009, pp. 1155-1434. 3. T. Uno, K. Sugimoto, K. Sugawara and T. Tateishi, The role of cytochrome P2C19 in R-warfarin pharmacokinetics and its interaction with omeprazol, Ther. Drug Monit. 30 (2008) 276-281; DOI: 10.1097/FTD.0b013e31816e2d8e. 4. C. Bolego, R. Baetta, S. Bellosta, A. Corsini and R. Paoletti, Safety considerations for

REFERENCES 1. Martinez AI, Freeman PR, Moga DC. Statin Use and Gastrointestinal Hemorrhage: A Large Retrospective Cohort Study. Am J Cardiovasc Drugs . 2018 Sep 26. doi: 10.1007/s40256-018-0301-4. [Epub ahead of print] 2. Smith I, Schmidt R, Halm EA, Mansi IA. Do Statins Increase the Risk of Esophageal Conditions? Findings from Four Propensity Score-Matched Analyses. Clin Drug Investig . 2018;38:135-146. 3. Kuoppala J, Lamminpaa A, Pukkala E. Statins and cancer: A systematic review and meta-analysis. Eur J Cancer . 2008;44:2122-2132. 4. Browning DR, Martin RM

: 8816722 16. Friis H, Andreasen PB. Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987. J Intern Med 1992;232:133-8. doi: 10.1111/j.1365-2796.1992.tb00562.x 17. Golomb BA, Evans MA. Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs 2008;8:373-418. doi: 10.2165/0129784-200808060-0000 18. Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005;42:481-9. doi: 10

. Wright D.J, Grayson A., Jackson M., et al. The reality of statin use in primary care. European Heart Journal- ESC Congress. 2002; 23 (1): 19. 28. McKenney JM., Jones PH., Adamczyk MA., et al for the STELLAR Study Group. Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial. Current medical research and opinion. 2003; 19(8): 1-10. 29. McKenney JM., McCormick LS., Schaefer EJ., et al. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic

Introduction Statins were discovered in the 1980s and are still used in clinical practice. They were first identified in the mitochondria by many independent teams [ 1 ]. Nowadays, statins are among the most popular medications. Their popularity is associated with the low cost of production as well as the high incidence of cardiovascular diseases, which they counteract by lowering the cholesterol level. Natural statins are secondary fungal metabolites. They are 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) inhibitors, blocking one of the steps of the

Clin Chem Lab Med 2010;48(12):1685–1691 2010 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2010.277 2010/090 Article in press - uncorrected proof Review Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance Luigi Marzio Biasucci*, Gina Biasillo and Antonella Stefanelli Institute of Cardiology, Catholic University of Sacred Heart, Rome, Italy Abstract Statins are one of the most important medications in cardio- vascular diseases since they block cholesterol synthesis by inhibiting the 3-hydroxy-3

References [1] Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C., BlackwellL., Emberson J., Holland L.E., Reith C., Bhala N., Peto R., Barnes E.H., Keech A., Simes J., Collins R., et al., Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 2010 , 376(9753), 1670-1681 [2] Wenger N., Lewis S.J., et al., Use of statin therapy to reduce cardiovascular risk in older patients. Curr. Gerontol. Geriatr. Res., 2010, 915296 [3] Kapur N.K., Musunuru K., et al

References 1. Lee R, Margaritis M, Channon KM, et al. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem. 2012;19:2504-20. 2. 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;63:2491-502. 3. Psarros C, Lee R, Margaritis M, et al. Nanomedicine for the prevention, treatment and imaging of atherosclerosis. Nanomedicine. 2012;8 Suppl 1:S59-68. 4. Antoniades C, Antonopoulos

REFERENCES 1. WALLEY T, FOLINO-GALLO P, STEPHENS P, VAN GANSE E. Trends in prescribing utilization of statins and other lipid lowering drugs across Europe 1997-2003 . Br J Clin Pharmacol 2005; 60 :543-51. 2. KILDEMOES HW, STØVRING H, ANDERSEN M. Driving forces behind increasing cardiovascular drug utilization: a dynamic pharmacoepidemiological model . Br J Clin Pharmacol 2008; 66 :885-95. 3. WALLEY T, FOLINO-GALLO P, SCHWABE U, VAN GANSE E. EUROMEDSTAT GROUP. Variations and increase in use of statins across Europe: data from administrative databases . BMJ

REFERENCES 1. BAIGENT C, KEECH A, KEARNEY PM, BLACKWELL L, BUCK G, POLLICINO C, et al . Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomized trials of statins . Lancet 2005; 366:1267–1278. 2. SHEPHERD J, COBBE SM, FORD I, ISLES CG, LARIMER AR, MACFARLANE PW, et al ., for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia . New Engl J Med 1995; 333:1301–7. 3. Scandinavian Simvastatin Survival