title: HDL re-examined.
abstract: OBJECTIVE
  To summarize the current evidence concerning the role of HDL-C and HDL-associated parameters in the risk for cardiovascular disease (CVD).
  
  
  RESULTS
  Numerous population studies have shown that plasma levels of HDL-C are inversely associated with CVD risk; in patient care HDL-C levels are therefore widely implemented in risk estimation models. A number of antiatherogenic properties have been ascribed to the HDL particle, but the hypothesis that HDL is causally related to CVD has been seriously challenged by recent data obtained from both human genetic studies and clinical trials. The final word on HDL-C as a therapeutic target is pending, as a number of clinical endpoint trials specifically focusing on the effect(s) of HDL-C increasing agents are underway. Moreover, recent data show that HDL efflux capacity could hold independent predictive value for CVD events, which clearly highlights the potential need to focus on HDL functionality, rather than on HDL-C levels.
  
  
  CONCLUSIONS
  The dogmatic concept that HDL-C levels predict future CVD events is undisputed, but the role of HDL-C as a causal factor in atherosclerosis has been challenged by a number of different types of studies. In recent years, a paradigm shift toward 'HDL functionality' is apparent. Whether or not optimizing these markers of HDL functionality actually does reduce CVD risk requires formal testing in prospective controlled studies.
authors.affiliation: aDepartment of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands bDepartment of Medicine and Genetics, Institute for Translational Medicine and Therapeutics, and Cardiovascular Institute, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA cDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D002986:Clinical Trials as Topic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D057847:Lipid Regulating Agents / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; D057847:Lipid Regulating Agents