title: Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on arterial compliance and distensibility in patients with mild-to-moderate chronic kidney disease.
abstract: BACKGROUND
  Arterial stiffness is increased in chronic kidney disease (CKD). Intervention studies aimed at reduction of arterial stiffness in dialysis patients have been disappointing. We therefore investigated the effect of pravastatin, vitamin E, and homocysteine lowering on arterial compliance and distensibility coefficients in mild-to-moderate CKD.
  
  
  METHODS
  This is a sub-study of the ATIC study, a randomized, double-blind trial in 93 CKD patients. The treatment group received pravastatin to which vitamin E supplementation was added after 6 months and homocysteine lowering therapy after another 6 months. Measurement of the distensibility coefficient (DC) and the compliance coefficient (CC) of the common carotid (CCA), femoral (FA) and brachial artery (BA) was performed at 0, 6, 12, 18 months. Young's elastic modulus (YEM) was measured in the common carotid artery.
  
  
  RESULTS
  After 18 months, CCA-DC increased from mean (SD) 15.15 (6.67) to 16.52 (6.37) × 10-3kPa-1 in the treatment and decreased from 18.44 (8.19) to 16.26 (7.35) in the placebo group (p = 0.057). CCA-CC increased from 0.64 (0.24) to 0.71 (0.26) mm2kPa-1 in the treatment and decreased from 0.77 (0.28) to 0.69 (0.25) in the placebo group (p < 0.0001). FA-DC had increased from 6.64 (3.45) to 11.46 (6.83) in the treatment group, and from 6.46 (2.85) to 7.08 (2.73) in the placebo group (p = 0.0001). FA-CC had increased from 0.46 (0.24) to 0.74 (0.44) in the treatment group, and from 0.48 (0.27) to 0.53 (0.21) in the placebo group (p = 0.008). BA-DC and CC, and CCA YEM were not significantly different between the groups.
  
  
  CONCLUSIONS
  In patients with mild-to-moderate CKD, 18 months of treatment consisting of pravastatin, vitamin E and homocysteine lowering resulted in significant improvement of compliance and distensibility in CCA and FA. Since pravastatin was used throughout the observation period, it remains unclear whether the beneficial effects are attributable solely to the ongoing effect of pravastatin treatment, or if the additional interventions further slowed the progression of vascular stiffness. Therefore, larger studies with a longer period of follow-up observing the separate effects are needed.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Susanna J E
authors.initials: SJ
authors.lastname: Veringa
authors.forename: Prabath W B
authors.initials: PW
authors.lastname: Nanayakkara
authors.forename: Frans J
authors.initials: FJ
authors.lastname: van Ittersum
authors.forename: Irene L
authors.initials: IL
authors.lastname: Vegting
authors.forename: Coen
authors.initials: C
authors.lastname: van Guldener
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000503:physiopathology; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage*; D059289:Vascular Stiffness / Q000187:drug effects*; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006710:Homocysteine; D014810:Vitamin E; D017035:Pravastatin