American Journal of Cardiology
Volume 104, Issue 10, Supplement , Pages 46E-51E , 16 November 2009

High-Density Lipoprotein Cholesterol as a Risk Factor and Target of Therapy after Acute Coronary Syndrome

  • Gregory G. Schwartz, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress for reprints: Gregory G. Schwartz, MD, PhD, Cardiology Section (111B), Veterans Affairs Medical Center, 1055 Clermont Street, Denver, Colorado 80220

References 

  1. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, 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–e181
  2. O'Donoghue M, Boden WE, Braunwald E, Cannon CP, Clayton TC, de Winter RJ, et al Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA. 2008;300:71–80
  3. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, 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
  4. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–1504
  5. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  6. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease: the Framingham Study. Am J Med. 1977;62:707–714
  7. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience): Prospective Cardiovascular Munster study. Am J Cardiol. 1992;70:733–737
  8. Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study (4S). Lancet. 1995;345:1274–1275
  9. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, 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
  10. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22
  11. Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, 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
  12. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–1310
  13. Tardif JC, McMurray JJ, Klug E, Small R, Schumi J, Choi J, et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:1761–1768
  14. de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, et al Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–1316
  15. Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC, Dai D, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157:111–117
  16. Olsson AG, Schwartz GG, Szarek M, Sasiela WJ, Ezekowitz MD, Ganz P, et al. High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial. Eur Heart J. 2005;26:890–896
  17. Wolfram RM, Brewer HB, Xue Z, Satler LF, Pichard AD, Kent KM, 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. Tziakas DN, Chalikias GK, Kaski JC, Kekes A, Hatzinikolaou EI, Stakos DA, et al. Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach. Atherosclerosis. 2007;193:196–203
  19. Ray KK, Cannon CP, Cairns R, Morrow DA, Ridker PM, Braunwald E. Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2009;29:424–430
  20. Tall AR. The effects of cholesterol ester transfer protein inhibition on cholesterol efflux. Am J Cardiol. 2008;104(suppl 10A):39E–45E
  21. Barter P. Metabolic abnormalities: high-density lipoproteins. Endocrinol Metab Clin North Am. 2004;33:393–403
  22. Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, 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
  23. Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007;297:1675–1682
  24. Sacks FM, Rudel LL, Conner A, Akeefe H, Kostner G, Baki T, et al Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J Lipid Res. 2009;50:894–907
  25. Waksman R, Kent K, Pichard A, Suddath W, Satler L, Martin D, et al 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. 2009;118(suppl 2):S371
  26. Esper RJ, Vilarino J, Cacharron JL, Machado R, Ingino CA, Garcia Guinazu CA, et al. Impaired endothelial function in patients with rapidly stabilized unstable angina: assessment by noninvasive brachial artery ultrasonography. Clin Cardiol. 1999;22:699–703
  27. Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, et al. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002;105:1399–1402
  28. Imazu M, Ono K, Tadehara F, Kajiwara K, Yamamoto H, Sumii K, et al. Plasma levels of oxidized low density lipoprotein are associated with stable angina pectoris and modalities of acute coronary syndrome. Int Heart J. 2008;49:515–524
  29. Johnston N, Jernberg T, Lagerqvist B, Siegbahn A, Wallentin L. Oxidized low-density lipoprotein as a predictor of outcome in patients with unstable coronary artery disease. Int J Cardiol. 2006;113:167–173
  30. Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2001;21:473–480
  31. Brambilla M, Camera M, Colnago D, Marenzi G, De Metrio M, Giesen PL, et al. Tissue factor in patients with acute coronary syndromes: expression in platelets, leukocytes, and platelet-leukocyte aggregates. Arterioscler Thromb Vasc Biol. 2008;28:947–953
  32. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357:2482–2494
  33. Viswambharan H, Ming XF, Zhu S, Hubsch A, Lerch P, Vergeres G, et al. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. Circ Res. 2004;94:918–925
  34. Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res. 2006;98:1352–1364
  35. Buffon A, Biasucci LM, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med. 2002;347:5–12
  36. Puranik R, Bao S, Nobecourt E, Nicholls SJ, Dusting GJ, Barter PJ, et al. Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo. Atherosclerosis. 2008;196:240–247
  37. Theilmeier G, Schmidt C, Herrmann J, Keul P, Schafers M, Herrgott I, et al High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation. 2006;114:1403–1409
  38. Van Lenten BJ, Hama SY, de Beer FC, Stafforini DM, McIntyre TM, Prescott SM, et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response (Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures). J Clin Invest. 1995;96:2758–2767
  39. Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751–2756
  40. Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE). http://www.clinicaltrials.gov/ct2/show/NCT00461630?term=NCT00461630&rank=1
  41. Niacin Plus Statin to Prevent Vascular Events. http://www.clinicaltrials.gov/ct2/show?term=NCT00120289&rank=1
  42. Action to Control Cardiovascular Risk in Diabetes (ACCORD). http://www.clinicaltrials.gov/ct2/show/NCT00000620?term=NCT00000620&rank=1
  43. Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study). http://www.clinicaltrials.gov/ct2/show/NCT00212004?term=NCT00212004&rank=1
  44. Insulin Resistance Intervention After Stroke Trial (IRIS). http://www.clinicaltrials.gov/ct2/show/NCT00091949?term=NCT00091949&rank=1
  45. A Study of RO4607381 in Stable Coronary Heart Disease Patients with Recent Acute Coronary Syndrome. http://www.clinicaltrials.gov/ct2/show/NCT00658515?term=NCT00658515&rank=1
  46. de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002;105:2159–2165

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9149(09)02380-7

doi: 10.1016/j.amjcard.2009.09.019

American Journal of Cardiology
Volume 104, Issue 10, Supplement , Pages 46E-51E , 16 November 2009