Journal of Medical Ultrasonics

, Volume 29, Issue 4, pp 225–230 | Cite as

Short-term therapy with relatively low-dose cerivastatin improves endothelial function independently of its lipid-lowering effect: Evaluation of brachial artery vasodilatation using B-mode ultrasound imaging

  • Koichi Sakabe
  • Nobuo Fukuda
  • Teru Nada
  • Yukiko Onose
  • Takeshi Soeki
  • Hisanori Shinohara
  • Yoshiyuki Tamura
Case Report


Background and Objective

Administration of 0.4 to 0.8 mg of cerivastatin per day for 2 weeks has been reported to have pleiotropic effects and improve endothelial function. Whether low-dose cerivastatin would produce these rapid pleiotropic effects in the clinical setting remains uncertain, however. We investigated the effect of short-term therapy with relatively low-dose cerivastatin (0.15 mg/day) on endothelial function, thrombostatic parameters, and C-reactive protein (CRP) levels in hypercholesterolemic patients.


Thirteen patients with LDL-cholesterol>160 mg/dl were treated with daily doses of 0.15 mg of cerivastatin for 2 weeks. Endothelial function, thrombostatic parameters (tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-1], and CRP were estimated at baseline and again after 2 weeks of treatment. Endothelial function was measured as flow-mediated vasodilation. Flow-mediated vasodilatation was assessed by measuring the percent change in the diameter of the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Endothelium-independent vasodilatation was also measured using sublingual nitroglycerin.


No major complications developed after the treatment. Total cholesterol decreased significantly, from 258±32 to 211±21 mg/dl, and LDL-cholesterol also decreased from 171±15 to 133±16 mg/dl after the treatment. Flow-mediated vasodilatation increased significantly, from 4.6±1.3 percent to 8.7±3.5 percent after 2 weeks of therapy, although endothelium-independent vasodilatation was not affected (9.5±2.4% vs 8.8±3.1%). No relation was found between percent change in flow-mediated vasodilatation and improvement in levels of LDL-cholesterol after therapy (r=0.07). PAI-1, t-PA, and CRP were not significantly changed by 2 weeks of therapy.


(1) Evaluating vasodilation of the brachial artery with B-mode ultrasound imaging was useful in investigating the effect of statin on endothelial function. (2) Although no effect was detected in PAI-1, t-PA, or CRP, relatively low-dose cerivastatin therapy for 2 weeks improved endothelial function and lipid level independently and safely in hypercholesterolemic patients.


B-mode ultrasound brachial artery cholesterol endothelial function statins 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Shepherd J, Cobbe SM, Ford I, et al: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med 1995;333: 1301–1307.PubMedCrossRefGoogle Scholar
  2. 2).
    Sacks FM, Pfeffer MA, Moye LA, et al: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.N Engl J Med 1996;335: 1001–1009.PubMedCrossRefGoogle Scholar
  3. 3).
    WOS-COPS Study Group. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study.Circulation 1998;97: 1440–1445.Google Scholar
  4. 4).
    Egashira K, Hirooka Y, Kai H, et al: Reduction in serum cholesterol with pravastatin improves endothelial-dependent coronary vasomotion in patients with hypercholesterolemia.Circulation 1994;89: 2519–2524.PubMedGoogle Scholar
  5. 5).
    John S, Delles C, Jacobi J, et al: Rapid improvement of nitric oxide bioavailability after lipid-lowering therapy with cerivastatin within two weeks. J Am Coll Cardiol 2001;37: 1351–1358.PubMedCrossRefGoogle Scholar
  6. 6).
    Aikawa M, Rabkin E, Sugiyama S, et al: An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro.Circulation 2001;103: 276–283.PubMedGoogle Scholar
  7. 7).
    Ridker PM, Rifai N, Pfeffer MA, et al: Long-term effects of pravastatin on plasma concentration of C-reactive protein.Circulation 1999;100: 230–235.PubMedGoogle Scholar
  8. 8).
    Ridker PM, Rifai N, Lowenthal SP: Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia.Circulation 2001;103: 1191–1193.PubMedGoogle Scholar
  9. 9).
    Tsunekawa T, Hayashi T, Kano H, et al: Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days.Circulation 2001;104: 376–379.PubMedGoogle Scholar
  10. 10).
    Hunninghake D, Insull W, Knopp R, et al: Comparison of the efficacy of atorvastatin versus cerivastatin in primary hypercholesterolemia.Am J Cardiol 2001;88: 635–639.PubMedCrossRefGoogle Scholar
  11. 11).
    Matsuda Y, Akita H, Terashima M, et al: Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease.Am Heart J 2000;140: 753–759.PubMedCrossRefGoogle Scholar
  12. 12).
    Zeiher AM, Drexler H, Saurbier B, et al: Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension.J Clin Invest 1993;92: 652–662.PubMedGoogle Scholar
  13. 13).
    Egashira K, Inou T, Hirooka Y, et al: Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions.J Clin Invest 1993;91: 29–37.PubMedCrossRefGoogle Scholar
  14. 14).
    Laufs U, Fata VL, Plutzky J, et al: Upregulation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors.Circulation 1998;97: 1129–1135.PubMedGoogle Scholar
  15. 15).
    Gonzalez-Fernandez F, Jimenez A, Lopez-Blaya A, et al: Cerivastatin prevents tumor necrosis factor-α-induced downregulation of endothelial nitric oxide synthase: role of endothelial cytosolic proteins.Atherosclerosis 2001;155: 61–70.PubMedCrossRefGoogle Scholar
  16. 16).
    Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al: Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.J Clin Invest 1998;101: 2711–2719.PubMedGoogle Scholar
  17. 17).
    Kaesemeyer WH, Caldwell RB, Huang J, et al: Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. J Am Coll Cardiol 1999;33: 234–241.PubMedCrossRefGoogle Scholar
  18. 18).
    Lacoste L, Lam JY, Hung J, et al: Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction.Circulation 1995;92: 3172–3177.PubMedGoogle Scholar
  19. 19).
    Strandberg TE, Vanhanen H, Tikkanen MJ: Effect of statins on C-reactive protein in patients with coronary artery disease.Lancet 1999;100: 230–235.Google Scholar
  20. 20).
    Furberg CD, Pitt B: Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001;2: 205–207.PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Society of Ultrasonics in Medicine 2002

Authors and Affiliations

  • Koichi Sakabe
    • 1
  • Nobuo Fukuda
    • 1
  • Teru Nada
    • 1
  • Yukiko Onose
    • 1
  • Takeshi Soeki
    • 1
  • Hisanori Shinohara
    • 1
  • Yoshiyuki Tamura
    • 1
  1. 1.Department of Cardiology and Clinical ResearchNational Zentsuji HospitalKagawaJapan

Personalised recommendations