title: Effects of fluvastatin on plasma levels of low-density lipoprotein subfractions, oxidized low-density lipoprotein, and soluble adhesion molecules: a twenty-four-week, open-label, dose-increasing study.
abstract: BACKGROUND
  Statins not only lower low-density lipoprotein (LDL) levels, but also have several antiarteriosclerotic effects (eg, decreasing arterial inflammation and arterial smooth muscle cell proliferation, as well as antioxidant effects). The relationship between the dose of statin and its effects on plasma LDL levels and other arteriosclerosis-related effects remains to be clarified.
  
  
  OBJECTIVE
  We investigated the effect of a statin, fluvastatin, on plasma levels of lipoprotein subfractions, oxidized LDL (Ox-LDL), Ox-LDL immunoglobulin G (IgG), soluble adhesion molecules, reverse cholesterol transport (ie, transport of esterified high-density lipoprotein cholesterol [HDL-C] to triglyceride [TG]-rich lipoproteins by cholesteryl ester transfer protein [CETP] and reduction of plasma HDL-C levels), and on the intima-medial thickness (IMT) of the common carotid arteries.
  
  
  METHODS
  Patients with nonfamilial type 2 hyperlipoproteinemia were eligible for this open-label, dose-increasing study. Fluvastatin 20 mg/d was administered for the first 12 weeks, and the daily dose was increased to 40 mg for the subsequent 12 weeks. Patients were examined at baseline and after 12 and 24 weeks of treatment. Plasma lipoprotein subfractions were determined using sequential ultracentrifugation at 100,000g. The plasma levels of Ox-LDL, Ox-LDL-IgG, CETP, and soluble adhesion molecules were measured using sandwich enzyme-linked immunosorbent assay. The maximum IMT of the common carotid arteries was measured using sonography.
  
  
  RESULTS
  The plasma levels of LDL cholesterol (LDL-C) and apolipoprotein (apo) B were reduced by 25% and 17%, respectively (P<0.001 for both), after 12 weeks of treatment with fluvastatin 20 mg/d; no further significant reductions in LDL were observed after increasing the daily dose to 40 mg. Fluvastatin 20 mg/d for 12 weeks decreased plasma levels of intermediate-density lipoprotein cholesterol, LDL-I-C, LDL-II-C, and LDL-III-C by 25% (P<0.01), 30% (P<0.001), 23% (P<0.01), and 20% (P = 0.02), respectively. No further significant reductions in these levels were observed after increasing the daily dose to 40 mg. The plasma levels of Ox-LDL decreased in a similar fashion to the plasma levels of LDL-C (P<0.001). However, plasma levels of Ox-LDL-IgG and soluble P-selectin did not decrease after 12 weeks of fluvastatin 20 mg/d, but did decrease significantly (both 22%) after the next 12 weeks of treatment with fluvastatin 40 mg/d (P<0.05). Plasma levels of intercellular adhesion molecule 1and vascular cell adhesion molecule 1 and CETP mass were not altered by fluvastatin treatment. Significant changes in maximum IMT of the common carotid arteries were not seen throughout 24 weeks of fluvastatin treatment.
  
  
  CONCLUSIONS
  In this patient population, fluvastatin 20 mg/d was sufficient to significantly reduce plasma levels of LDL, the 3 LDL subfractions, and Ox-LDL, but was not sufficient to reduce plasma levels of Ox-LDL-IgG and soluble P-selectin. It is important to check not only plasma lipoprotein levels but also other factors relating to arteriosclerosis during treatment with statins for the prevention and treatment of arteriosclerosis.
authors.affiliation: Department of Internal Medicine, Tokai University School of Medicine, Boseidai, Isehara, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.affiliation: Department of Internal Medicine, Tokai University School of Medicine, Boseidai, Isehara, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iizuka
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Kamon
authors.initials: K
authors.lastname: Iigaya
keywords: adhesion molecules; carotid arteriosclerosis; fluvastatin; lipoprotein subfractions; oxidized LDL; reverse cholesterol transport