Current Atherosclerosis Reports

, Volume 12, Issue 5, pp 301–307

Lessons from Coronary Intravascular Ultrasound on the Importance of Raising High-Density Lipoprotein Cholesterol

  • Stephen J. Nicholls
  • Kiyoko Uno
  • E. Murat Tuzcu
  • Steven E. Nissen
Article

Abstract

Technological advances have enhanced our ability to visualize the entire extent of atherosclerosis within the artery wall. Intravascular ultrasound has enabled characterization of the impact of medical therapies on progression of coronary atherosclerosis. Despite use of established anti-atherosclerotic therapy, cardiovascular disease still remains the leading cause of morbidity and mortality. There is an ongoing need to develop new therapeutic strategies to achieve more effective reduction in cardiovascular risk. Raising high-density lipoprotein cholesterol continues to receive attention as a therapeutic strategy. The relationship between high-density lipoprotein and progression of atherosclerosis and its implications for clinical practice are reviewed here.

Keywords

HDL Intravascular ultrasound Risk factors Imaging Atherosclerosis 

References

  1. 1.
    Lloyd-Jones D, Adams R, Carnethon M, et al.: Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009, 119:e21–181.CrossRefPubMedGoogle Scholar
  2. 2.
    Baigent C, Keech A, Kearney PM, et al.: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005, 366:1267–1278.CrossRefPubMedGoogle Scholar
  3. 3.
    Neal B, MacMahon S, Chapman N: Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000, 356:1955–1964.CrossRefPubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 5.
    Gordon DJ, Rifkind BM: High-density lipoprotein--the clinical implications of recent studies. N Engl J Med 1989, 321:1311–1316.PubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Barter P, Gotto AM, LaRosa JC, et al.: HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007, 357:1301–1310.CrossRefPubMedGoogle Scholar
  8. 8.
    Wilson PW, D’Agostino RB, Levy D, et al.: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97:1837–1847.PubMedGoogle Scholar
  9. 9.
    Badimon JJ, Badimon L, Galvez A, et al.: High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab Invest 1989, 60:455–461.PubMedGoogle Scholar
  10. 10.
    Badimon JJ, Badimon L, Fuster V: Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J Clin Invest 1990, 85:1234–1241.CrossRefPubMedGoogle Scholar
  11. 11.
    Nicholls SJ, Cutri B, Worthley SG, et al.: Impact of short-term administration of high-density lipoproteins and atorvastatin on atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol 2005, 25:2416–2421.CrossRefPubMedGoogle Scholar
  12. 12.
    Plump AS, Scott CJ, Breslow JL: Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A 1994, 91:9607–9611.CrossRefPubMedGoogle Scholar
  13. 13.
    Rubin EM, Krauss RM, Spangler EA, et al.: Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 1991, 353:265–267.CrossRefPubMedGoogle Scholar
  14. 14.
    Rong JX, Li J, Reis ED, et al.: Elevating high-density lipoprotein cholesterol in apolipoprotein E-deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content. Circulation 2001, 104:2447–2452.CrossRefPubMedGoogle Scholar
  15. 15.
    Shah PK, Yano J, Reyes O, et al.: High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization. Circulation 2001, 103:3047–3050.CrossRefPubMedGoogle Scholar
  16. 16.
    Zannis VI, Chroni A, Krieger M: Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. J Mol Med (Berlin) 2006, 84:276–294.Google Scholar
  17. 17.
    Barter PJ, Nicholls S, Rye KA, et al.: Antiinflammatory properties of HDL. Circ Res 2004, 95:764–772.CrossRefPubMedGoogle Scholar
  18. 18.
    van der Wal AC, Becker AE, van der Loos CM, Das PK: Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994, 89:36–44.PubMedGoogle Scholar
  19. 19.
    Waters D, Craven TE, Lesperance J: Prognostic significance of progression of coronary atherosclerosis. Circulation 1993, 87:1067–1075.PubMedGoogle Scholar
  20. 20.
    Tuzcu EM, Schoenhagen P: Atherosclerosis imaging: intravascular ultrasound. Drugs 2004, 64(Suppl 2):1–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Mintz GS, Nissen SE, Anderson WD, et al.: American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001, 37:1478–1492.CrossRefPubMedGoogle Scholar
  22. 22.
    Nissen SE, Tuzcu EM, Schoenhagen P, et al.: Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005, 352:29–38.CrossRefPubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    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.CrossRefPubMedGoogle Scholar
  25. 25.
    Nicholls SJ, Tuzcu EM, Sipahi I, et al.: Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007, 297:499–508.CrossRefPubMedGoogle Scholar
  26. 26.
    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.CrossRefPubMedGoogle Scholar
  27. 27.
    Nicholls SJ, Tuzcu EM, Sipahi I, et al.: Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J Am Coll Cardiol 2006, 47:992–997.CrossRefPubMedGoogle Scholar
  28. 28.
    Tardif JC, Gregoire J, L’Allier PL, et al.: Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007, 297:1675–1682.CrossRefPubMedGoogle Scholar
  29. 29.
    Waksman RK, Pichard A: A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high density lipoprotein plasma infusions in patients with acute coronary syndrome. Circulation 2008, 118:S_371 [abstract 1697].Google Scholar
  30. 30.
    Sacks FM, Rudel LL, Conner A, et al.: Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J Lipid Res 2009, 50:894–907.CrossRefPubMedGoogle Scholar
  31. 31.
    Boekholdt SM, Kuivenhoven JA, Wareham NJ, et al.: Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study. Circulation 2004, 110:1418–1423.CrossRefPubMedGoogle Scholar
  32. 32.
    Morehouse LA, Sugarman ED, Bourassa PA, et al.: Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. J Lipid Res 2007, 48:1263–1272.CrossRefPubMedGoogle Scholar
  33. 33.
    Barter PJ, Caulfield M, Eriksson M, et al.: Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007, 357:2109–2122.CrossRefPubMedGoogle Scholar
  34. 34.
    Nissen SE, Tardif JC, Nicholls SJ, et al.: Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007, 356:1304–1316.CrossRefPubMedGoogle Scholar
  35. 35.
    Bots ML, Visseren FL, Evans GW, et al.: Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007, 370:153–160.CrossRefPubMedGoogle Scholar
  36. 36.
    Nicholls SJ, Tuzcu EM, Brennan DM, et al.: Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation 2008, 118:2506–2514.CrossRefPubMedGoogle Scholar
  37. 37.
    Vergeer M, Bots ML, van Leuven SI, et al.: Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: a pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials. Circulation 2008, 118:2515–2522.CrossRefPubMedGoogle Scholar
  38. 38.
    James WP, Astrup A, Finer N, et al.: Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000, 356:2119–2125.CrossRefPubMedGoogle Scholar
  39. 39.
    Dattilo AM, Kris-Etherton PM: Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 1992, 56:320–328.PubMedGoogle Scholar
  40. 40.
    Nissen SE, Nicholls SJ, Wolski K, et al.: Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 2008, 299:1547–1560.CrossRefPubMedGoogle Scholar
  41. 41.
    Nicholls SJ, Hsu A, Wolski K, et al.: Baseline lipid levels and progression of coronary atherosclerosis in abdominally obese patients. J Am Coll Cardiol 2009, 53:A200.CrossRefGoogle Scholar
  42. 42.
    Taylor AJ, Sullenberger LE, Lee HJ, et al.: 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, 110:3512–3517.CrossRefPubMedGoogle Scholar
  43. 43.
    Taylor AJ, Lee HJ, Sullenberger LE: The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006, 22:2243–2250.CrossRefPubMedGoogle Scholar
  44. 44.
    Frick MH, Elo O, Haapa K, et al.: 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.PubMedGoogle Scholar
  45. 45.
    Rubins HB, Robins SJ, Collins D, et al.: 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.CrossRefPubMedGoogle Scholar
  46. 46.
    Elkeles RS, Diamond JR, Poulter C, et al.: Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. Diabetes Care 1998, 21:641–648.CrossRefPubMedGoogle Scholar
  47. 47.
    Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001, 357:905–910.Google Scholar
  48. 48.
    Nissen SE, Nicholls SJ, Wolski K, et al.: Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008, 299:1561–1573.CrossRefPubMedGoogle Scholar
  49. 49.
    Nicholls SJ, Hu T, Kupfer S, et al.: Lowering of the triglyceride/HDL cholesterol ratio predicts the benefit of pioglitazone on progression of coronary atherosclerosis in diabetic patients. Circulation 2008, 118:S_1135.CrossRefGoogle Scholar
  50. 50.
    Mazzone T, Meyer PM, Feinstein SB, et al.: Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006, 296:2572–2581.CrossRefPubMedGoogle Scholar
  51. 51.
    Davidson M, Meyer PM, Haffner S, et al.: Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation 2008, 117:2123–2130.CrossRefPubMedGoogle Scholar
  52. 52.
    King AC, Haskell WL, Young DR, et al.: Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation 1995, 91:2596–2604.PubMedGoogle Scholar
  53. 53.
    Leon AS, Connett J, Jacobs DR Jr, Rauramaa R: Leisure-time physical activity levels and risk of coronary heart disease and death. The Multiple Risk Factor Intervention Trial. JAMA 1987, 258:2388–2395.CrossRefPubMedGoogle Scholar
  54. 54.
    Blair SN, Kohl HW 3rd, Paffenbarger RS Jr, et al.: Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA 1989, 262:2395–2401.CrossRefPubMedGoogle Scholar
  55. 55.
    Maeda K, Noguchi Y, Fukui T: The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med 2003, 37:283–290.CrossRefPubMedGoogle Scholar
  56. 56.
    Meksawan K, Pendergast DR, Leddy JJ, et al.: Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women. J Am Coll Nutr 2004, 23:131–140.PubMedGoogle Scholar
  57. 57.
    Lichtenstein AH: Dietary fat and cardiovascular disease risk: quantity or quality? J Women Health 2003, 12:109–114.CrossRefGoogle Scholar
  58. 58.
    Tani S, Nagao K, Anazawa T, et al.: Coronary plaque regression and lifestyle modification in patients treated with pravastatin. Assessment mainly by daily aerobic exercise and an increase in the serum level of high-density lipoprotein cholesterol. Circ J 2010, 74:954–961.CrossRefPubMedGoogle Scholar
  59. 59.
    Bloedon LT, Dunbar R, Duffy D, et al.: Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients. J Lipid Res 2008, 49:1344–1352.CrossRefPubMedGoogle Scholar
  60. 60.
    Joseph SB, McKilligin E, Pei L, et al.: Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A 2002, 99:7604–7609.CrossRefPubMedGoogle Scholar
  61. 61.
    deLemos AS, Wolfe ML, Long CJ, et al.: Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol. Circulation 2002, 106:1321–1326.CrossRefPubMedGoogle Scholar
  62. 62.
    Nicholls SJ: HDL: still a target for new therapies? Curr Opin Investig Drugs 2008, 9:950–956.PubMedGoogle Scholar
  63. 63.
    Nair A, Kuban BD, Tuzcu EM, et al.: Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002, 106:2200–2206.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Stephen J. Nicholls
    • 1
    • 2
    • 3
  • Kiyoko Uno
    • 1
  • E. Murat Tuzcu
    • 1
  • Steven E. Nissen
    • 1
  1. 1.Department of Cardiovascular Medicine, Heart & Vascular InstituteCleveland ClinicClevelandUSA
  2. 2.Cell BiologyCleveland ClinicClevelandUSA
  3. 3.Center for Cardiovascular Diagnostics and PreventionCleveland ClinicClevelandUSA

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