Focusing on High-Density Lipoprotein for Coronary Heart Disease Risk Reduction

Cardiology Clinics

Volumn 29, Issue 1, 2011, Pages 105-122

  Davidson, Michael H ^a,b  

^a Pritzker School of Medicine   (United States)

^b RADIANT RESEARCH   (United States)

Author keywords

Coronary heart disease; High density lipoprotein cholesterol; High density lipoprotein particles; Reverse cholesterol transport; Risk reduction

Indexed keywords

ANACETRAPIB; ANTILIPEMIC AGENT; ATORVASTATIN; AVASIMIBE; CERENIS; CERIVASTATIN; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CSC 111; CSC 112; D 4F; DALCETRAPIB; ETC 216; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIVER X RECEPTOR AGONIST; NICOTINIC ACID; PACTIMIBE; PITAVASTATIN; PLACEBO; PROSTAGLANDIN INHIBITOR; ROSUVASTATIN; RVX 208; TORCETRAPIB; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; AEROBIC EXERCISE; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CAROTID ATHEROSCLEROSIS; CHOLESTEROL TRANSPORT; COMBINATION CHEMOTHERAPY; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; DRUG BIOAVAILABILITY; DRUG DOSE TITRATION; DRUG ELUTING STENT; DRUG ERUPTION; DRUG FATALITY; DRUG INDUCED HEADACHE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SELECTIVITY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSLIPIDEMIA; DYSPEPSIA; FAMILIAL HYPERCHOLESTEROLEMIA; FLUSHING; GALLSTONE; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL SYMPTOM; GOUT; HEART PROTECTION; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPERTRIGLYCERIDEMIA; HYPERURICEMIA; INCIDENCE; ISCHEMIC HEART DISEASE; LIFESTYLE MODIFICATION; LIPOPROTEIN METABOLISM; LIVER TOXICITY; METABOLIC SYNDROME X; MONOTHERAPY; MYOPATHY; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; PATIENT COMPLIANCE; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; RISK FACTOR; RISK REDUCTION; SIDE EFFECT; SKIN DISEASE; SMOKING CESSATION; WEIGHT REDUCTION;

ANTICHOLESTEREMIC AGENTS; CORONARY DISEASE; HUMANS; INCIDENCE; LIPOPROTEINS, HDL; PROGNOSIS; RISK FACTORS; UNITED STATES;

EID: 78751635637     PISSN: 07338651     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccl.2010.11.005     Document Type: Review

References (53)

1. American Heart Association Heart disease and stroke statistics-2009 update 2009, American Heart Association, Dallas (TX).
2. Smith S.C., Allen J., Blair S.N., et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006, 113:2363-2372.
3. Duffy D., Rader D.J. Update on strategies to increase HDL quantity and function. Nat Rev Cardiol 2009, 6:455-463.
4. Davidson M.H., Toth P.P. High-density lipoprotein metabolism: potential therapeutic targets. Am J Cardiol 2007, 100(11A):n32-n40.
5. Davidson M.H. Focus on HDL as a therapeutic target for CAD risk reduction. Am J Cardiol 2009, 104(Suppl 10):1E-2E.
6. National Cholesterol Education Panel 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.
7. Castelli W.P. Cholesterol and lipids in the risk of coronary heart disease: the Framingham Heart Study. Can J Cardiol 1988, 4(Suppl A):5A-10A.
8. Castelli W.P., Garrison R.J., Wilson P.W.F., et al. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986, 256:2835-2838.
9. Stampfer M.J., Sacks F.M., Salvin S., et al. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med 1991, 325:373-381.
10. Goldbourt U., Yaari J.S., Medalie J.H. Isolated low HDL cholesterol as a risk factor for coronary heart disease mortality: a 21-year follow-up of 8,000 men. Arterioscler Thromb Vasc Biol 1997, 17:107-113.
11. Vergeer M., Holleboom A.G., Kastelein J.J., et al. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?. J Lipid Res 2010, 51(8):2058-2073.
12. Davidson M.H. Targeting high-density lipoprotein cholesterol in the management of cardiovascular disease. Am Heart Hosp J 2007, 5:210-216.
13. Birjmohun R.S., Hutten B.A., Kastelein J.J., et al. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds. J Am Coll Cardiol 2005, 45:185-197.
14. LaRosa J.C., He J., Vuppiuturi S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 1999, 282:2340-2346.
15. Gordon D.J., Probstfield J.L., Garrison R.J., et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989, 79:8-15.
16. Schwartz G.G., Olsson A.G., Szarek M., et al. Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: an analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial. Diabetes Care 2005, 28:2508-2513.
17. Wolfram R.M., Brewer H.B., Xue Z., et al. Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation. Am J Cardiol 2006, 98:711-717.
18. Shah P.K., Kaul S., Nilsson J., et al. Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: an idea whose time for testing is coming, part I. Circulation 2001, 104:2376-2383.
19. Barter P.J., Nicholls S., Rye K.A., et al. Antiinflammatory properties of HDL. Circ Res 2004, 95:764-772.
20. Singh I.M., Shishehbor M.H., Ansell B.J., et al. High density lipoprotein as a therapeutic target: a systematic review. JAMA 2007, 298:786-798.
21. Cuchel M., Rader D.J. Genetics of increased HDL cholesterol levels: insights into the relationship between HDL metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2003, 23:1710-1712.
22. Toth P.P. High density lipoprotein as a therapeutic target: clinical evidence and treatment strategies. Am J Cardiol 2005, 96(9A):50K-58K.
23. Davidson M.H., Rosenson R.S. Novel targets that affect high-density lipoprotein metabolism: the next frontier. Am J Cardiol 2009, 104(10 Suppl):52E-57E.
24. Study of Coronary Atheroma by Intravascular Ultrasound: effect of Rosuvastatin Versus Atorvastatin (SATURN) Available at:, Accessed October 30, 2010. http://clinicaltrials.gov/ct2/show/NCT00620542.
25. Ridker P.M., Buring J.E., Cook N.R., et al. C-reactive protein, the metabolic syndrome, and risk of incident cardiovasculr events. Circulation 2003, 107:391-397.
26. Blake G.J., Otvos J.D., Rifai N., et al. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation 2002, 106:1930-1937.
27. Mora S., Ridker P.M. Justification for the use of statins in primary prevention: an intervention trial evaluating rosuvastatin (JUPITER)-can C-reactive protein be used to statin therapy in primary prevention?. Am J Cardiol 2006, 97(2A):33A-71A.
28. Berge K.G., Canner P.L. Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Eur J Clin Pharmacol 1991, 40(Suppl 1):S49-S51.
29. Kamanna V.S., Kashyap M.L. Mechanism of action of niacin on lipoprotein metabolism. Curr Atheroscler Rep 2000, 2:36-46.
30. Pike N.B. Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. J Clin Invest 2005, 115(12):3400-3403.
31. 2 in response to nicotinic acid. J Invest Dermatol 2006, 126:2637-2646.
32. Narumiya S., Sugimoto Y., Ushikubi F., et al. Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999, 79:1193-1226.
33. 2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc Natl Acad Sci U S A 2006, 103:6682-6687.
34. 2 in vivo in humans following the administration of nicotinic acid prostaglandins. J Invest Dermatol 1989, 38:263-274.
35. Shepherd J., Betteridge J., Van Gaal L., European Consensus Panel 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.
36. Taylor A.J., Sullenberger L.E., Lee H.J., et al. Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2. Circulation 2004, 110:3512-3517.
37. Jones P.H., Cusi K., Davidson M.H., et al. Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials. Am J Cardiovasc Drugs 2010, 10:73-84.
38. Davidson M.H., Rooney M.W., Drucker J., et al. Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. Clin Ther 2009, 12:2824-2838.
39. Davidson M.H. Update on CETP inhibition. J Clin Lipidol 2010, 4:394-398.
40. Tardiff J.C., Gregoire J., L'Allier P.L., et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007, 297:1675-1682.
41. DeGoma EM, Rader DJ. Novel HDL-directed pharmacotherapeutic strategies. Nat Rev Cardiol, in press.
42. Qiu X., Mistry A., Ammirati M.J., et al. Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules. Nat Struct Mol Biol 2007, 14:106-113.
43. Tall A.R. The effects of cholesterol ester transfer protein inhibition on cholesterol efflux. Am J Cardiol 2009, 104(Suppl):39E-45E.
44. Nicholls S.J. High-density lipoprotein and progression rate of atherosclerosis in intravascular ultrasound trials. Am J Cardiol 2009, 104(Suppl):16E-21E.
45. Kastelein J.J., van Leuven S.I., Burgess L., RADIANCE 1 Investigators, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007, 356:1620-1630.
46. Barter P. Lessons learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Am J Cardiol 2009, 104(Suppl):10E-15E.
47. Vergeer M., Stroes E.S. The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors. Am J Cardiol 2009, 104(Suppl):32E-38E.
48. Okamoto H., Yonemori F., Wakitani K., et al. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 2000, 406:203-207.
49. Cannon C.P., Dansky H.M., Davidsom M.H. Design of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib. Am Heart J 2009, 158:513-519.
50. Schwartz G.G., Olsson A.G., Ballantyne C.M., dal-OUTCOMES Committees and Investigators, et al. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009, 158:896-901.
51. DAL-vessel A Study of the Effect of RO4607381 on atherosclerotic plaque in patients with coronary heart disease Available at:, Accessed October 10, 2010. http://www.clinicaltrials.gov/ct2/show/NCT00655473%3Fterm%3Ddalcetrapib%2BAND%2Bvessel%26rank%3D1.
52. DAL-plaque A Study of the Effect of RO4607381 on atherosclerotic plaque in patients with coronary heart disease Available at:, Accessed October 10, 2010. http://www.clinicaltrials.gov/ct2/show/NCT00655473%3Fterm%3Ddalcetrapib%2BAND%2Bplaque%26rank%3D1.
53. Motazacker M.M., Kastelein J.J., Kuivenhoven J.A. Are high-density lipoprotein genes and their products targets for therapy?. Curr Opin Lipidol 2010, 21:157-158.