Pleiotropic effects: Should statins be considered an essential component in the treatment of dyslipidemia?
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Cardiovascular disease (CVD) is the leading cause of death in the developed world. Lower risks of morbidity and mortality in trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) have changed the conventional wisdom regarding lipid lowering. Since 2001, there have been surprising results concerning the early benefits of stain therapy, which suggest that some benefits may be derived from effects other than those of simply improving dyslipidemias. The earlier than expected CVD benefits from statin trials have led to the theory that statins have effects other than, or concomitant to, the benefits on serum lipid levels, and that these effects may be at least partly responsible for their early and often significant reduction in CVD risk. These have been defined as pleiotropic effects. Possible means by which statins reduce CVD risk independent of their lipid regulation may include antithrombotic and anti-inflammatory effects, antioxidation, plaque stabilization, and endothelial wall relaxation resulting in lower intra-arterial pressure and increased blood flow.
- The Expert Panel: Report of the National Cholesterol Educational Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988, 148: 36–69. CrossRef
- National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994, 89:1329–1445.
- Dujovne CA: The clinical-therapeutic implications of the Scandinavian Simvastatin Survival Study. Am J Cardiol 1997, 79:1387–1388. CrossRef
- Downs JR, Learfield M, Weis S, et al., for the AFCAPS/TexCAPS Research Group: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998, 279:1615–1622. CrossRef
- Shepherd J, Cobbe SM, Ford I, et al., for the West of Scotland Coronary Prevention Study Group: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995, 333:1301–1307. CrossRef
- Third Report National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation 2002, 106:3143.
- Ray KK, Cannon CP: The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes. J Am Coll Cardiol 2005, 46:1425–1433. CrossRef
- Shepherd J, Blauw GJ, Murphy MB, et al., PROSPER study group: Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. PROspective Study of Pravastatin in the Elderly at Risk. Lancet 2002, 360:1623–1630. CrossRef
- Sever PS, Dahlof B, Poulter NR, et al., ASCOT investigators: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003, 361:1149–1158. CrossRef
- Nissen SE, Nicholls SJ, Sipahi I, et al., for the ASTEROID Investigators: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006, 295:1556–1565. CrossRef
- Auer J, Berent R, Weber T, et al.: Clinical significance of pleiotropic effects of statins: lipid reduction and beyond. Curr Med Chem 2002, 9:1831–1850.
- Kamai T, Metsumoto N, Koitabashi Y, et al.: Pleiotropic effects of 3-hydroxy-3-mehtylglutaryl-coenzyme A reductase inhibitors: candidate mechanisms for anti-lipid deposition in blood vessels. Curr Med Chem 2005, 3:195–201.
- Liao JK: Effects of statins on HMG-CoA reductase inhibition beyond low-density lipoprotein cholesterol. Am J Cardiol 2005, 96(suppl):24F–33F. CrossRef
- Zucker ML, Trowbridge C, Krehbeil P, et al.: Platelet function in hypercholesterolemics before and after hypolipidemic drug therapy. Haemostasis 1986, 16:57–64.
- Davignon J, Leiter LA: Ongoing clinical trials of the pleiotropic effects of statins. Vasc Health Risk Manag 2005, 1:29–40. CrossRef
- Ray KK, Cannon CP, Ganz P: Beyond lipid lowering: what have we learned about the benefits of statins from the acute coronary syndromes trials? Am J Cardiol 2006, 98(Suppl):18P–25P. CrossRef
- Wierzbicki AS, Lumb PJ, Semra YK, et al.: Effect of atorvastatin on plasma fibrinogen. Lancet 1998, 351:569–570. CrossRef
- Golledge J, Greenhalhg RM, Davies AH: The symptomatic carotid plaque. Circulation 2000, 31:774–781.
- Bocan TM: Pleiotropic effects of HMG-CoA reductase inhibitors. Curr Opin Invest Drugs 2002, 3:1312–1317.
- Solomon DH, Karlson EW, Rimm EB, et al.: Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003, 107:1303–1307. CrossRef
- del Rincon ID, Williams K, Stern MP, et al.: High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001, 44:2737–2745. CrossRef
- Ray KK, Cannon CP: Early time to benefit with intensive statin treatment: could it be the pleiotropic effects? Am J Cardiol 2005, 96(Suppl):54F–60F. CrossRef
- Ridker PM, Cannon CP, Morrow D, et al.: C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005, 352:20–28. CrossRef
- Sander D, Winbeck K, Klingelhofer J, et al.: Reduced progression of early carotid atherosclerosis after antibiotic treatment and Chlamydia pneumoniae seropositivity. Circulation 2002, 106:2428–2433. CrossRef
- Ridker PM: C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol 2007, 49:2129–2138. CrossRef
- Kinlay S: Low-density lipoprotein-dependent and-independent effects of cholesterol-lowering therapies on C-reactive protein. J Am Coll Cardiol 2007, 49:2003–2009. CrossRef
- Tsimikas S: Oxidative biomarkers in the diagnosis and prognosis of cardiovascular disease. Am J Cardiol 2006, 98(Suppl):9P–17P. CrossRef
- Mason RP: Molecular basis of differences among statins and a comparison with antioxidant vitamins. Am J Cardiol 2006, 98(Suppl):34P–41P. CrossRef
- Libby P, Sasiela W: Plaque stabilization: can we turn theory into evidence? Am J Cardiol 2006, 98(Suppl):26P–33P. CrossRef
- Brown G, Albers J, Fisher L, et al.: Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990, 323:1289–1298. CrossRef
- Mehta JL: Pleiotropic effects of statins: how important are they in the prevention of vascular disease? Endothelium 2003, 10:3–4. CrossRef
- Arora R, Liebo M, Maldonado F: Statin-induced myopathy: the two faces of Janus. J Cardiovasc Pharmacol Ther 2006, 11:105–112. CrossRef
- Olson KL, Brand DW, McGinnis B, et al.: A determination of the reasons why patients discontinue statin therapy [abstract 58]. Paper presented at the American College of Clinical Pharmacy Annual Meeting. San Francisco, California; October 23–26, 2005.
- Lesaffre E, Kocmanova D, Lemos PA, et al.: A retrospective analysis of the effect of noncompliance on time to first major adverse cardiac event in LIPS. Clin Ther 2003, 25:2431–2447. CrossRef
- Spencer FA, Fonarow GC, Frederick PD, et al.: Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction. Arch Intern Med 2004, 164:2162–2168. CrossRef
- McGowan MP; TNT Study Group: There is no evidence for an increase in acute coronary syndromes after short-term abrupt discontinuation of statins in stable cardiac patients. Circulation 2004, 110:2280–2282. CrossRef
- Puccetti L, Pasqui AL, Pastorelli, et al.: Platelet hyperactivity after statin treatment discontinuation. Thromb Haemost 2003, 90:476–482.
- Chu CS, Lee KT, Lee MY, et al.: Effects of atorvastatin and atorvastatin withdrawal on soluble DC40L and adipocytokines in patients with hypercholeserolaemia. Acta Cardiol 2006, 61:263–269. CrossRef
- Cubeddu LX, Seamon MJ: Statin withdrawal: clinical implications and molecular mechanisms. Pharmacotherapy 2006, 26:1288–1296. CrossRef
- Taneva E, Borucki K, Wiens L, et al.: Early effects on endothelial function of atorvastatin 40 mg twice daily and its withdrawal. Am J Cardiol 2006, 97:1002–1006. CrossRef
- Vogel RA: Measurement of endothelial function by brachial artery flow-mediated vasodilation. Am J Cardiol 2001, 88:31E–34E. CrossRef
- Chapman MJ, Assmann G, Fruchart JC, et al.: Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid? A position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 2004, 20:1253–1268. CrossRef
- Lakshman MR, Gottipati CS, Narasimhan SJ, et al.: Inverse correlation of serum paraoxonase and homocysteine thiolactonase activities and antioxidant capacity of high-density lipoprotein with the severity of cardiovascular disease in persons with type 2 diabetes mellitus. Metabolism 2006, 55:1201–1206. CrossRef
- Lupattelli G, Marchesi S, Lombardini R, et al.: Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia. Metabolism 2003, 52:1191–1195. CrossRef
- Okopie AB, Haberka M, Madej A, et al.: Extralipid effects of micronized fenofibrate in dyslipidemic patients. Pharmacol Rep 2006, 58:729–735.
- Olsson AG, Schwartz GG, Szarek M, et al.: High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial. Eur Heart J 2005, 26:890–896. CrossRef
- Mendez M, LaPointe MC: PPAR inhibition of cyclooxygenase-2, PGE2 synthase, and inducible nitric oxide synthase in cardiac myocytes. Hypertension 2003, 42:844–850. CrossRef
- Nesto RW, Plutzky J: The vascular effects of TZDs: stabilizing plaque in an unstable environment. Online CME presentation by the University of Wisconsin School of Medicine and Public Health. Released April 26, 2006. Available at http://www.medscape.com/viewprogram/5173. Accessed on September 13, 2007.
- Dujovne CA: Side effects of statins: hepatitis vs transaminitis, myositis vs CPKitis. Am J Cardiol 2002, 89:1411–1413. CrossRef
- Shepherd J: Who should receive a statin these days? J Intern Med 2006, 260:305–319. CrossRef
- Pleiotropic effects: Should statins be considered an essential component in the treatment of dyslipidemia?
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