title: Treatment options for low high-density lipoproteins.
abstract: OBJECTIVE
  To examine the current and future therapeutic option of HDL-based therapies.
  
  
  RESULTS
  The inverse association between plasma level of high-density lipoprotein cholesterol (HDL-C) is strong and coherent across the population studied. In-vitro and in-vivo studies show the strong biological plausibility for HDL as a therapeutic target. Mendelian randomization does not support HDL-C as a causal (protective) cardiovascular risk factor, and clinical data does not support the concept that raising HDL-cholesterol mass alters the outcomes. Better biomarkers of HDL function are being examined in the clinical trials. These include cellular cholesterol efflux, antioxidant and anti-inflammatory effects, effects on vascular endothelial cells (inflammation and nitric oxide release) and endothelial progenitor cells. Novel therapeutic agents that alter HDL function are in advanced phase 3 trials and in early preclinical trials. These include inhibitors of cholesteryl ester transfer protein, reconstituted proteoliposomes, apolipoprotein A-I and HDL mimetic peptides and small molecules that increase apo A-I production rate.
  
  
  CONCLUSIONS
  Targeting HDL-C has, to date, not led to changes in the cardiovascular outcomes. Novel therapeutic advances target the HDL function. In keeping with the recent 2013 American College of Cardiology/American Heart Association Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults, the major focus of prevention lies with LDL-cholesterol reduction.
authors.affiliation: McGill University Health Center/Royal Victoria Hospital, Montreal, Quebec, Canada.
authors.forename: Anouar
authors.initials: A
authors.lastname: Hafiane
authors.forename: Samantha
authors.initials: S
authors.lastname: Kellett
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006951:Hyperlipoproteinemias / Q000628:therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D009525:Niacin / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D009525:Niacin