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High-density lipoprotein subfractions and risk of coronary artery disease

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Abstract

Numerous studies have shown that levels of high-density lipoprotein (HDL) cholesterol are inversely related to coronary artery disease risk. The HDL subfractions, however, seem to differ in their capacity to confer protection, with the large HDL2 subfraction appearing to be more important than the small HDL3 subfraction. Lipid-modifying drugs differ in their HDL-raising efficacy, and they also differ in how they affect HDL subfractions. Clinical trials show that raising total HDL cholesterol improves clinical and angiographic outcomes. It remains to be determined, however, whether a shift in distribution of HDL particles provides greater benefit than just an increase in total HDL.

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References and Recommended Reading

  1. Maron DJ: The epidemiology of low levels of high-density lipoprotein cholesterol in patients with and without coronary artery disease. Am J Cardiol 2000, 86(suppl): 11L-14L.

    Article  PubMed  CAS  Google Scholar 

  2. Gordon T, Castelli WP, Hjortland MC, et al.: High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977, 62: 707–714.

    Article  PubMed  CAS  Google Scholar 

  3. Castelli WP: Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study. Can J Cardiol 1988, 4(suppl A): 5A-10A.

    PubMed  Google Scholar 

  4. Gordon DJ, Probstfield JL, Garrison RJ, et al.: High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989, 79: 8–15.

    PubMed  CAS  Google Scholar 

  5. Toth PP: Reverse cholesterol transport: high-density lipoprotein’s magnificent mile. Curr Atheroscler Rep 2003, 5: 386–393.

    PubMed  Google Scholar 

  6. Kwiterovich PO Jr: Lipoprotein heterogeneity: diagnostic and therapeutic implications. Am J Cardiol 2002, 90: 1i-10i.

    Article  PubMed  CAS  Google Scholar 

  7. Gotto AM Jr, Brinton EA: Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update. J Am Coll Cardiol 2004, 43: 717–724.

    Article  PubMed  CAS  Google Scholar 

  8. Otvos JD, Jeyarajah EJ, Cromwell WC: Measurement issues related to lipoprotein heterogeneity. Am J Cardiol 2002, 90(suppl): 22i-29i.

    Article  PubMed  CAS  Google Scholar 

  9. Otvos JD: Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy. Clin Lab 2002, 48: 171–180.

    PubMed  CAS  Google Scholar 

  10. Asztalos BF, Schaefer EJ: High-density lipoprotein subpopulations in pathologic conditions. Am J Cardiol 2003, 91(suppl): 12E-17E.

    Article  PubMed  CAS  Google Scholar 

  11. Vega GL, Grundy SM: Hypoalphalipoproteinemia (low high density lipoprotein) as a risk factor for coronary heart disease. Curr Opin Lipidol 1996, 7: 209–216.

    Article  PubMed  CAS  Google Scholar 

  12. Reichl D, Miller NE: Pathophysiology of reverse cholesterol transport: insights from inherited disorders of lipoprotein metabolism. Arteriosclerosis 1989, 9: 785–797.

    PubMed  CAS  Google Scholar 

  13. Genest J Jr, Bard JM, Fruchart JC, et al.: Familial hypoalphalipoproteinemia in premature coronary artery disease. Arterioscler Thromb 1993, 13: 1728–1737.

    PubMed  Google Scholar 

  14. O’Brien T, Nguyen TT, Hallaway BJ, et al.: The role of lipoprotein A-I and lipoprotein A-I/A-II in predicting coronary artery disease. Arterioscler Thromb Vasc Biol 1995, 15: 228–231.

    PubMed  CAS  Google Scholar 

  15. Gotto AM Jr, Whitney E, Stein EA, et al.: Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 2000, 101: 477–484.

    PubMed  CAS  Google Scholar 

  16. Bolibar I, von Eckardstein A, Assmann G, Thompson S: Short-term prognostic value of lipid measurements in patients with angina pectoris. The ECAT Angina Pectoris Study Group: European Concerted Action on Thrombosis and Disabilities. Thromb Haemost. 2000, 84: 955–960.

    PubMed  CAS  Google Scholar 

  17. Drexel H, Amann FW, Rentsch K, et al.: Relation of the level of high-density lipoprotein subfractions to the presence and extent of coronary artery disease. Am J Cardiol 1992, 70: 436–440.

    Article  PubMed  CAS  Google Scholar 

  18. Salonen JT, Salonen R, Seppänen K, et al.: HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction: a prospective population study in eastern Finnish men. Circulation 1991, 84: 129–139.

    PubMed  CAS  Google Scholar 

  19. Freedman DS, Otvos JD, Jeyarajah EJ, et al.: Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease. Arterioscler Thromb Vasc Biol 1998, 18: 1046–1053.

    PubMed  CAS  Google Scholar 

  20. Rosenson RS, Otvos JD, Freedman DS: Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol 2002, 90: 89–94.

    Article  PubMed  CAS  Google Scholar 

  21. Robins SJ, Collins D, Wittes JT, et al., for the VA-HIT Study Group: Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. JAMA 2001, 285: 1585–1591.

    Article  PubMed  CAS  Google Scholar 

  22. Ginsberg HN: Insulin resistance and cardiovascular disease. J Clin Invest 2000, 106: 453–458.

    PubMed  CAS  Google Scholar 

  23. Garvey WT, Kwon S, Zheng D, et al.: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 2003, 52: 453–462.

    Article  PubMed  CAS  Google Scholar 

  24. Ginsberg HN: Nonpharmacologic management of low levels of high-density lipoprotein cholesterol. Am J Cardiol 2000, 86: 41L-45L.

    Article  PubMed  CAS  Google Scholar 

  25. Ginsberg HN, Kris-Etherton P, Dennis B, et al., for the DELTA Research Group: Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Arterioscler Thromb Vasc Biol 1998, 18: 441–449.

    PubMed  CAS  Google Scholar 

  26. Sillanaukee P, Koivula T, Jokela H, et al.: Alcohol consumption and its relation to lipid-based cardiovascular risk factors among middle-aged women: the role of HDL3 cholesterol. Atherosclerosis 2000, 152: 503–510.

    Article  PubMed  CAS  Google Scholar 

  27. Kamanna VS, Kashyap ML: Mechanism of action of niacin on lipoprotein metabolism. Curr Atheroscler Rep 2000, 2: 36–46.

    PubMed  CAS  Google Scholar 

  28. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the 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: 3143–3421.

    Google Scholar 

  29. Morgan JM, Capuzzi DM, Baksh RI, et al.: Effects of extended-release niacin on lipoprotein subclass distribution. Am J Cardiol 2003, 91: 1432–1436.

    Article  PubMed  CAS  Google Scholar 

  30. Knopp RH, Alagona P, Davidson M, et al.: Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism 1998, 47: 1097–1104.

    Article  PubMed  CAS  Google Scholar 

  31. Crouse JR III, Frohlich J, Ose L, et al.: Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol 1999, 83: 1476–1477.

    Article  PubMed  CAS  Google Scholar 

  32. Johansson J, Mölgaard J, Olsson AG: Plasma high density lipoprotein particle size alteration by simvastatin treatment in patients with hypercholesterolaemia. Atherosclerosis 1991, 91: 175–184.

    Article  PubMed  CAS  Google Scholar 

  33. Staels B, Dallongeville J, Auwerx J, et al.: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998, 98: 2088–2093.

    PubMed  CAS  Google Scholar 

  34. Vu-Dac N, Schoonjans K, Kosykh V, et al.: Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995, 96: 741–750.

    Article  PubMed  CAS  Google Scholar 

  35. Asztalos BF, Horvath KV, McNamara JR, et al.: Effects of atorvastatin on the HDL subpopulation profile of coronary heart disease patients. J Lipid Res 2002, 43: 1701–1707.

    Article  PubMed  CAS  Google Scholar 

  36. Brown G, Albers JJ, Fisher LD, 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.

    PubMed  CAS  Google Scholar 

  37. Brown BG, Zhao XQ, Chait A, et al.: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001, 345: 1583–1592.

    Article  PubMed  CAS  Google Scholar 

  38. Asztalos BF, Batista M, Horvath KV, et al.: Change in a1 HDL concentration predicts progression in coronary artery stenosis. Arterioscler Thromb Vasc Biol 2003, 23: 847–852.

    Article  PubMed  CAS  Google Scholar 

  39. Rubins HB, Robins SJ, Collins D, et al., for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999, 341: 410–418.

    Article  PubMed  CAS  Google Scholar 

  40. Syvänne M, Nieminen MS, Frick MH, et al., for the Lopid Coronary Angiography Trial (LOCAT) Study Group: Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol. Circulation 1998, 98: 1993–1999.

    PubMed  Google Scholar 

  41. Ruotolo G, Ericsson CG, Tettamanti C, et al.: Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT). J Am Coll Cardiol 1998, 32: 1648–1656.

    Article  PubMed  CAS  Google Scholar 

  42. Krause BR, Auerbach BJ: Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis. Curr Opin Invest Drug 2001, 2: 375–381.

    CAS  Google Scholar 

  43. Nissen SE, Tsunoda T, Tuzcu EM, et al.: Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003, 290: 2292–2300.

    Article  PubMed  CAS  Google Scholar 

  44. Brousseau ME, Schaefer EJ, Wolfe ML, et al.: Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 2004, 350: 1505–1515.

    Article  PubMed  CAS  Google Scholar 

  45. Rittershaus CW, Miller DP, Thomas LJ, et al.: Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol 2000, 20: 2106–2112.

    PubMed  CAS  Google Scholar 

  46. Barter PJ, Brewer HB Jr, Chapman MJ, et al.: Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 2003, 23: 160–167.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Sidney Kimmel Laboratory for Preventive Cardiology, Thomas Jefferson University - Jefferson Heart Institute, 925 Chestnut Street, 19107, Philadelphia, PA, USA

    John Morgan MD

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  1. John Morgan MD
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  2. Christina Carey PA-C
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  3. Anne Lincoff MD
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  4. David Capuzzi MD, PhD
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Morgan, J., Carey, C., Lincoff, A. et al. High-density lipoprotein subfractions and risk of coronary artery disease. Curr Atheroscler Rep 6, 359–365 (2004). https://doi.org/10.1007/s11883-004-0047-0

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