title: High-density lipoprotein cholesterol raising: does it matter?
abstract: OBJECTIVE
  Cardiovascular disease (CVD) is the leading cause of morbidity and premature mortality in Europe and the United States, and is increasingly common in developing countries. High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for CVD and is superior to low-density lipoprotein cholesterol (LDL-C) as a predictor of cardiovascular events. The residual risk conferred by low HDL-C in patients with a satisfactory LDL-C was recently highlighted by the European Atherosclerosis Society. Despite the lack of randomized controlled trials, it has been suggested that raising the level of HDL-C should be considered as a therapeutic strategy in high-risk patients because of the strong epidemiological evidence, compelling biological plausibility, and both experimental and clinical research supporting its cardioprotective effects.
  
  
  RESULTS
  Three recent large randomized clinical trials investigating the effect of HDL-C raising with niacin and dalcetrapib in statin-treated patients failed to demonstrate an improvement in cardiovascular outcomes.
  
  
  CONCLUSIONS
  There is evidence to support the view that HDL functionality and the mechanism by which a therapeutic agent raises HDL-C are more important than plasma HDL-C levels. Future therapeutic agents will be required to improve this functionality rather than simply raising the cholesterol cargo.
authors.affiliation: Cardiovascular Trials Unit, Central Manchester University Hospitals, Manchester, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schofield
authors.forename: Michael
authors.initials: M
authors.lastname: France
authors.forename: Basil
authors.initials: B
authors.lastname: Ammori
authors.forename: Yifen
authors.initials: Y
authors.lastname: Liu
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
mesh_terms: D000577:Amides; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood*; D004952:Esters; D006801:Humans; D009525:Niacin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D040242:Risk Reduction Behavior; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D004952:Esters; D013438:Sulfhydryl Compounds; D009525:Niacin; C411602:dalcetrapib