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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
  • 29 Downloads

Abstract

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.

Methods

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.

Results

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.

Conclusions

(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.

Keywords

B-mode ultrasound brachial artery cholesterol endothelial function statins 

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References

  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

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