title: Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis.
abstract: BACKGROUND
  It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk.
  
  
  RESULTS
  We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).
  
  
  CONCLUSIONS
  Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.
authors: Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL (K.M.A.W.); Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France (P.A.); Global Pharmaceuticals Pfizer, New York, NY (D.A.D.); Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (A.M.T.); Department of Biochemistry and Lipid Clinic, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia (D.R.S.); NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia (A.K.); Medical Research Institute, University of Dundee, Dundee, United Kingdom (H.M.C.); Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (G.A.H.); Department of Medicine, Royal Free and University College Medical School, London, United Kingdom (D.J.B.); School of Biomedicine, University of Manchester, Manchester, United Kingdom (P.N.D.); Touro University, Mare Island, CA (M.B.C.); Department of Medicine, University of Texas Health Science Center, and VERDICT, South Texas Veterans Health Care System, San Antonio, TX (J.R.D.); and Weill Cornell Medical College, New York, NY (A.M.G.).
authors: S Matthijs
authors: SM
authors: Boekholdt
authors: Benoit J
authors: BJ
authors: Arsenault
authors: G Kees
authors: GK
authors: Hovingh
authors: Samia
authors: S
authors: Mora
authors: Terje R
authors: TR
authors: Pedersen
authors: John C
authors: JC
authors: Larosa
authors: K M A
authors: KM
authors: Welch
authors: Pierre
authors: P
authors: Amarenco
authors: David A
authors: DA
authors: Demicco
authors: Andrew M
authors: AM
authors: Tonkin
authors: David R
authors: DR
authors: Sullivan
authors: Adrienne
authors: A
authors: Kirby
authors: Helen M
authors: HM
authors: Colhoun
authors: Graham A
authors: GA
authors: Hitman
authors: D John
authors: DJ
authors: Betteridge
authors: Paul N
authors: PN
authors: Durrington
authors: Michael B
authors: MB
authors: Clearfield
authors: John R
authors: JR
authors: Downs
authors: Antonio M
authors: AM
authors: Gotto
authors: Paul M
authors: PM
authors: Ridker
authors: John J P
authors: JJ
authors: Kastelein
mesh_terms: D000789:Angina, Unstable / Q000453:epidemiology / Q000517:prevention & control; D016632:Apolipoprotein A-I / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D058729:Peripheral Arterial Disease / Q000453:epidemiology / Q000517:prevention & control; D016016:Proportional Hazards Models; D012307:Risk Factors; D040242:Risk Reduction Behavior; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides
keywords: apolipoproteins; cardiovascular diseases; high-density lipoprotein cholesterol; meta-analysis
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