Overview of Evidence Supporting the Treatment of Hyperlipidemia

  • Brian V. Reamy


Multiple basic science studies have established that atherosclerosis is much more than the mere accumulation of excess lipid in the walls of arteries leading to progressive narrowing of the vessel. Instead, it should be thought of as an inflammatory disease involving many cellular and molecular responses. Inflammatory cells and mediators participate at every stage of atherogenesis, from the earliest fatty streak to the most advanced fibrous lesion [1]. Elevated glucose, increased blood pressure, and inhaled cigarette by-products can trigger and perpetuate inflammation. However, one of the key factors triggering this inflammation is oxidized LDL (low density lipoprotein). When excess LDL is taken up by macrophages, it triggers the release of inflammatory mediators that can lead to thickening and/or rupture of plaque lining the arterial walls. Ruptured or unstable plaques are responsible for clinical events such as myocardial infarction and stroke. Lipid lowering, whether...


Statin Therapy Coronary Heart Disease Event Coronary Heart Disease Mortality Heart Protection Study Secondary Prevention Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–126.PubMedCrossRefGoogle Scholar
  2. 2.
    Forrester JS. Prevention of plaque rupture: a new paradigm of therapy. Ann Intern Med 2002;137:823–833.PubMedGoogle Scholar
  3. 3.
    Kavey RW, Daniels SR, Lauer RM, et al. American Heart Association Guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation 2003;107:1562–1566.PubMedCrossRefGoogle Scholar
  4. 4.
    Anonymous. Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990;264:3018–3024.Google Scholar
  5. 5.
    Mahoney LT, Burns TL, Stanford W, et al. Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol 1996;27:277–284.PubMedCrossRefGoogle Scholar
  6. 6.
    Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study. N Engl J Med 1998;338:1650–1656.PubMedCrossRefGoogle Scholar
  7. 7.
    Li S, Chen W, Srinivasan SR, et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood. JAMA 2003;290:2271–2277.PubMedCrossRefGoogle Scholar
  8. 8.
    Obarzanek E, Kimm SY, Barton BA, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated LDL cholesterol: seven year results of the Dietary Intervention Study in Children (DISC). Pediatrics 2001;107:256–264.PubMedCrossRefGoogle Scholar
  9. 9.
    Flynn BS, Warden JK, Secker-Walker R. Cigarette smoking prevention: effects of mass media and school interventions. J Health Educ 1995;26:545–551.Google Scholar
  10. 10.
    Sallis JF, McKenzie TL, Alcarez JE, et al. The effects of a 2-year physical education program (SPARK) on physical activity and fitness in elementary school students. Am J Public Health 1997;87:1328–1334.PubMedCrossRefGoogle Scholar
  11. 11.
    Stein EA, Illingsworth DR, Kwiterovich PO, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholsterolemia: a randomized controlled trial. JAMA 1999;281:137–144.PubMedCrossRefGoogle Scholar
  12. 12.
    Wiegman A, Hutten BA, Groot ED, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia. JAMA 2004;292:331–337.PubMedCrossRefGoogle Scholar
  13. 13.
    Anonymous. The Lipid Research Clinics Coronary Primary Prevention Trial results. JAMA 1984;251(3):351–364.CrossRefGoogle Scholar
  14. 14.
    Blankenhorn DH, Nessim SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 1987;257(23):3233–3240.PubMedCrossRefGoogle Scholar
  15. 15.
    Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study. N Engl J Med 1987;317:1237–1245.PubMedCrossRefGoogle Scholar
  16. 16.
    Anonymous. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984;2:600–604.Google Scholar
  17. 17.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301–1307.PubMedCrossRefGoogle Scholar
  18. 18.
    Downs JR, Clearfield M, Weis S, et al. 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.PubMedCrossRefGoogle Scholar
  19. 19.
    Scandanavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389.Google Scholar
  20. 20.
    The Lipid Study Group. LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) Study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris. Am J Cardiol 1995;76:474–479.Google Scholar
  21. 21.
    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;335:1001–1009.PubMedCrossRefGoogle Scholar
  22. 22.
    Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. JAMA 2001;285;1585–1591.PubMedCrossRefGoogle Scholar
  23. 23.
    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;285:1711–1718.PubMedCrossRefGoogle Scholar
  24. 24.
    Anonymous. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled trial. Lancet 2003;361: 2005–2015.CrossRefGoogle Scholar
  25. 25.
    Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–1504.PubMedCrossRefGoogle Scholar
  26. 26.
    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;291:1071–1080.PubMedCrossRefGoogle Scholar
  27. 27.
    LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–1435.PubMedCrossRefGoogle Scholar
  28. 28.
    Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction. IDEAL study: a randomized controlled trial. JAMA 2005;294:2437–2445.PubMedCrossRefGoogle Scholar
  29. 29.
    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;295:1556–1565.PubMedCrossRefGoogle Scholar
  30. 30.
    Cannon CP, Steinberg BA, Murphy SA, et al. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol 2006;48:438–445.PubMedCrossRefGoogle Scholar
  31. 31.
    Anonymous. 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: 1267–1277.CrossRefGoogle Scholar
  32. 32.
    Pignone M. Primary prevention: dyslipidemia. In: British Medical Journal. Clinical evidence, 15th edn. London: BMJ Publishing Group, 2006:38–40.Google Scholar
  33. 33.
    Gami A. Secondary prevention of ischemic cardiac events. In: British Medical Journal. Clinical evidence, 15th edn. London: BMJ Publishing Group, 2006:43–48.Google Scholar
  34. 34.
    Smith SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. Circulation 2006;113:2363–2372.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Brian V. Reamy
    • 1
  1. 1.Chair and Associate Professor, Department of Family MedicineUniformed Services University of the Health SciencesMaryland

Personalised recommendations