title: Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis.
abstract: BACKGROUND
  To evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.
  
  
  METHODS
  We meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.
  
  
  RESULTS
  Compared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): -5.31%, 95% CI -7.09 to -3.53%, P<0.001] and higher carotid IMT (pooled MD: 0.12mm, 95% CI 0.09-0.15mm, P<0.001) and femoral IMT (pooled MD: 0.35mm, 95% CI 0.18-0.51mm, P<0.001). FCH patients had lower FMD and increased IMT (pooled MD: -3.60%, 95% CI -6.69 to -0.50%, P=0.023; and 0.06mm, 95% CI 0.04-0.08mm, P<0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86-7.92%, P<0.001) and decreased carotid IMT (pooled MD of change: -0.025mm, 95% CI -0.042 to -0.009mm, P=0.003). Changes of both FMD and IMT with statins correlated with the duration×treatment intensity product in FH patients (both P<0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43-3.69%, P=0.013). No significant publication bias was detected.
  
  
  CONCLUSIONS
  Arterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.
authors.affiliation: 1st Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece. kmasoura@gmail.com
authors.forename: Constantina
authors.initials: C
authors.lastname: Masoura
authors.forename: Christos
authors.initials: C
authors.lastname: Pitsavos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Aznaouridis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Skoumas
authors.forename: Charalambos
authors.initials: C
authors.lastname: Vlachopoulos
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000328:Adult; D001158:Arteries / Q000473:pathology*; D050197:Atherosclerosis / Q000628:therapy; D001916:Brachial Artery / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005263:Femoral Artery / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000473:pathology; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors