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.
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.
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Koichi
K
Sakabe
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Nobuo
N
Fukuda
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Teru
T
Nada
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Yukiko
Y
Onose
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Takeshi
T
Soeki
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Hisanori
H
Shinohara
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, 765-8507, Kagawa, Japan.
Yoshiyuki
Y
Tamura
B-mode ultrasound; brachial artery; cholesterol; endothelial function; statins