Exp Clin Endocrinol Diabetes 2005; 113(8): 414-417
DOI: 10.1055/s-2005-865940
Mini-Review

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Beyond LDL-Cholesterol: HDL-Cholesterol as a Target for Atherosclerosis Prevention

K. G. Parhofer1
  • 1Department of Internal Medicine II, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany
Further Information

Publication History

Publication Date:
08 September 2005 (online)

Abstract

Dyslipoproteinemias such as elevated LDL-cholesterol, reduced HDL-cholesterol, elevated triglycerides and elevated lipoprotein(a) play a central role in atherosclerosis. An elevated LDL concentration is pro-atherogenic because LDL are intimately linked to oxidative and inflammatory processes in the arterial wall. HDL on the other hand are anti-atherogenic because they mediate cholesterol efflux from the arterial wall, modulate the metabolism of atherogenic lipoproteins, and directly affect endothelial function. The current therapeutic focus is on LDL reduction and much less on HDL elevation, although fibrates and particularly nicotinic-acid/niacin are potent drugs to increase HDL-cholesterol and although both groups of drugs have been proven beneficial in large end-point studies. Furthermore, new HDL raising drugs are being developed. In patients with established atherosclerosis or at high risk for atherosclerosis statin-based LDL reduction will remain the cornerstone of lipid therapy, but many patients may benefit from combination therapy aiming at optimizing all lipid parameters.

References

  • 1 American Diabetes Association . Clinical practice recommendations 2005.  Diab Care. 2005;  28 (Suppl 1) 4-37
  • 2 Avorn J. Torcetrapib and atorvastatin - should marketing drive the research agenda?.  N Engl J Med. 2005;  352 2573-2576
  • 3 Barter P J, Nicholls S, Rye K A, Anantharamaiah G M, Navab M, Fogelman A M. Antiinflammatory properties of HDL.  Circ Res. 2004;  95 764-772
  • 4 BIP Study Investigation . Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study.  Circulation. 2000;  102 21-27
  • 5 Birjmohun R S, Hutten B A, Kastelein J J, Stroes E S. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds.  J Am Coll Cardiol. 2005;  45 185-197
  • 6 Carlson L A, Rosenhamer G. Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid.  Acta Med Scand. 1988;  223 405-418
  • 7 Coronary Drug Project . Clofibrate and niacin in coronary heart disease.  JAMA. 1975;  231 360-381
  • 8 Deutsche Diabetes Gesellschaft . Praxisleitlinien.  Diab Stoffw. 2002;  11 (Suppl 2) 3-5
  • 9 Von Eckardstein A, Hersberger M, Rohrer L. Current understanding of the metabolism and biological actions of HDL.  Curr Opin Clin Nutr Metab Care. 2005;  8 147-152
  • 10 The Field Study Investigators . The need for a large-scale trial of fenofibrate therpy in diabetes: the rationale and design of the fenofibrate intervention and event lowering in Diabetes (FIELD) study.  Cardiovasc Diabetol. 2004;  1-11
  • 11 Frick M H, Elo O, Haapa K, Heinonen O P, Heinsalmi P, Helo P, Huttunen J K, Kaitaniemi P, Koskinen P, Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.  N Engl J Med. 1987;  317 1237-1245
  • 12 Frick M H, Syyanne M, Nieminen M S, Kauma H, Majajalme S, Virtanen V, Kesaniemi Y A, Pasternack A, Taskinen M R. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group.  Circulation. 1997;  96 2137-2143
  • 13 Kannel W B, Castelli W P, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study.  Ann Intern Med. 1979;  90 85-91
  • 14 Libby P, Theroux P. Pathophysiology of coronary artery disease.  Circulation. 2005;  111 3481-3488
  • 15 Linsel-Nitschke P, Tall A R. HDL as a target in the treatment of atherosclerotic cardiovascular disease.  Nature. 2005;  4 193-205
  • 16 Rubins H B, Robins S J, Collins D, Fye C L, Anderson J W, Elam M B, Faas F H, Linares E, Schaefer E J, Schectman G, Wilt T J, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.  N Engl J Med. 1999;  341 410-418
  • 17 Schatz H, Wehling M. Fighting against the “hypertriglyceridaemic waist”: a new international institute for the metabolic syndrome.  Exp Clin Endocrinol Diabetes. 2003;  111 119-120
  • 18 Shepherd J, Betteridge J, Van Gaal L. Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel.  Curr Med Res Opin. 2005;  21 665-682
  • 19 Taskinen M R. Diabetic dyslipidemia: from basic research to clinical practise.  Diabetologia. 2003;  46 733-749
  • 20 Taylor A J, Sullenberger L E, Lee H J, Lee J K, Grace K A. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins.  Circulation. 2004;  110 3509-3511
  • 21 Vrecer M, Turk S, Drinover J, Mrhar A. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials.  Int J Clin Pharmacol Ther. 2003;  12 567-577

Prof. Klaus G. Parhofer MD

Medical Department II - Großhadern
University Munich

Marchioninistraße 15

81377 Munich

Germany

Phone: + 498970953010

Fax: + 49 89 70 95 88 79

Email: Klaus.Parhofer@med.uni-muenchen.de

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