title: Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction.
abstract: Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels.
authors.affiliation: Cardiovascular Division, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4024, USA.
authors.forename: Vincent Y
authors.initials: VY
authors.lastname: See
authors.forename: David
authors.initials: D
authors.lastname: DeNofrio
authors.forename: Lee
authors.initials: L
authors.lastname: Goldberg
authors.forename: Gene
authors.initials: G
authors.lastname: Chang
authors.forename: Brett
authors.initials: B
authors.lastname: Sasseen
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kolansky
authors.forename: Faith
authors.initials: F
authors.lastname: Pickering
authors.forename: Andrew
authors.initials: A
authors.lastname: Kao
authors.forename: Evan
authors.initials: E
authors.lastname: Loh
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011184:Postoperative Period; D011758:Pyrroles / Q000494:pharmacology*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D007166:Immunosuppressive Agents; D011758:Pyrroles; D000069059:Atorvastatin; D009173:Mycophenolic Acid