title: Low plasma HDL-c, a vascular risk factor in high risk patients independent of LDL-c.
abstract: BACKGROUND
  High concentrations of high density lipoprotein-cholesterol (HDL-c) are associated with lower cardiovascular risk, but it is not known whether this is also the case in the presence of intensive low density lipoprotein-cholesterol (LDL-C) therapy. In this study, we determined the relationship between HDL-c and new non-fatal or fatal vascular events in patients with various manifestations of clinical evident vascular disease and evaluated whether this relationship is modified by LDL-c levels.
  
  
  METHODS
  Prospective single centre, cohort study of 3837 patients with a history or recent diagnosis of clinical manifest vascular disease (coronary, cerebrovascular, peripheral arterial disease or abdominal aortic aneurysm) The relationship between HDL-c quintiles and time to a new event (myocardial infarction, ischaemic stroke, vascular death) was quantified with Cox-regression models and adjusted for potential confounders (age, gender, body mass index, type 2 diabetes, triglycerides, smoking, use of alcohol and lipid-lowering therapy). Effect modification of LDL-c was assessed with interaction terms.
  
  
  RESULTS
  During a median follow up of 3.3 (range 0.1-9.5) years, a total of 465 first new events occurred. Compared with the lowest quintile, the upper quintile of HDL-c levels was associated with a lower risk for new events; Hazard Ratio 0.61 (95% CI 0.43-0.86) irrespective of the localisation of vascular disease and use of lipid-lowering medication. Higher HDL-c levels were associated with comparably lower risks for vascular events in patients with LDL-c levels above and below 2.5 mmol L(-1) (P-values for interaction > 0.05).
  
  
  CONCLUSIONS
  Patients with various clinical manifestations of vascular diseases in the highest HDL-c quintile have a lower risk for vascular events compared with patients in the lowest HDL-c quintile. Further, the current results expand the evidence by showing that also in a cohort of patients with various localisations of clinical evident vascular disease, in which statins were widely used, higher HDL-c levels confer a lower risk for developing new vascular events, irrespective of the localisation of vascular disease, use of lipid-lowering medication and plasma LDL-c concentration.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: G R
authors.initials: GR
authors.lastname: Hajer
authors.forename: Y
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: M L
authors.initials: ML
authors.lastname: Bots
authors.forename: A
authors.initials: A
authors.lastname: Algra
authors.forename: F L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood* / Q000401:mortality / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL