title: Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation).
abstract: OBJECTIVE
  This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT).
  
  
  BACKGROUND
  Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy.
  
  
  METHODS
  We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l).
  
  
  RESULTS
  In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02).
  
  
  CONCLUSIONS
  In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).
authors: Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania.
authors: Subroto
authors: S
authors: Acharjee
authors: William E
authors: WE
authors: Boden
authors: Pamela M
authors: PM
authors: Hartigan
authors: Koon K
authors: KK
authors: Teo
authors: David J
authors: DJ
authors: Maron
authors: Steven P
authors: SP
authors: Sedlis
authors: William
authors: W
authors: Kostuk
authors: John A
authors: JA
authors: Spertus
authors: Marcin
authors: M
authors: Dada
authors: Bernard R
authors: BR
authors: Chaitman
authors: G B John
authors: GB
authors: Mancini
authors: William S
authors: WS
authors: Weintraub
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood*; D002986:Clinical Trials as Topic; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008019:Life Style; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D009656:North America / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe
keywords: ACS; ATP; Adult Treatment Panel; BMI; CETP; HDL cholesterol; HDL-C; LDL-C; MI; OMT; PCI; SIHD; acute coronary syndrome(s); body mass index; cholesteryl ester transfer protein; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; myocardial infarction; optimal medical therapy; percutaneous coronary intervention; residual risk; stable ischemic heart disease
references: JAMA. 1984 Jan 20;251(3):351-64
references: 6361299
references: Am Heart J. 2006 Jun;151(6):1173-9
references: 16781214
references: J Am Coll Cardiol. 2005 Oct 4;46(7):1225-8
references: 16198835
references: J Am Coll Cardiol. 2012 Aug 7;60(6):517-20
references: 22796252
references: N Engl J Med. 2005 Apr 7;352(14):1425-35
references: 15755765
references: N Engl J Med. 1996 Oct 3;335(14):1001-9
references: 8801446
references: N Engl J Med. 2011 Dec 15;365(24):2255-67
references: 22085343
references: Lancet. 1994 Nov 19;344(8934):1383-9
references: 7968073
references: J Am Coll Cardiol. 2010 Mar 30;55(13):1348-58
references: 20338496
references: N Engl J Med. 2007 Sep 27;357(13):1301-10
references: 17898099
references: Atherosclerosis. 1996 Jul;124 Suppl:S11-20
references: 8831911
references: N Engl J Med. 1995 Nov 16;333(20):1301-7
references: 7566020
references: Lancet. 2006 Sep 9;368(9539):919-28
references: 16962881
references: Lancet. 2010 Jul 31;376(9738):333-9
references: 20655105
references: JAMA. 1998 May 27;279(20):1615-22
references: 9613910
references: J Am Coll Cardiol. 2004 Aug 4;44(3):720-32
references: 15358046
references: Circulation. 1989 Jan;79(1):8-15
references: 2642759
references: N Engl J Med. 2012 Nov 29;367(22):2089-99
references: 23126252
references: Am J Med. 1977 May;62(5):707-14
references: 193398
references: Eur Heart J. 2005 May;26(9):890-6
references: 15764620
references: N Engl J Med. 2007 Nov 22;357(21):2109-22
references: 17984165
references: Circulation. 1994 Mar;89(3):1333-445
references: 8124825
references: Ann Intern Med. 2010 Dec 21;153(12):800-8
references: 21173414
references: J Am Coll Cardiol. 2008 Jan 1;51(1):49-55
references: 18174036
references: JAMA. 2001 Mar 28;285(12):1585-91
references: 11268266
references: Lancet. 2005 Oct 8;366(9493):1267-78
references: 16214597
references: Am J Cardiol. 1980 Oct;46(4):649-54
references: 7416024
references: Am Heart J. 2009 Oct;158(4):513-519.e3
references: 19781408
references: N Engl J Med. 2007 Apr 12;356(15):1503-16
references: 17387127
references: Lancet. 2003 Apr 5;361(9364):1149-58
references: 12686036
references: JAMA. 1986 Nov 28;256(20):2835-8
references: 3773200
references: Lancet. 2010 Nov 13;376(9753):1670-81
references: 21067804
references: N Engl J Med. 2004 Apr 8;350(15):1495-504
references: 15007110