Simvastatin Treatment Improves Endothelial Function and ... - NCBI

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Financial support: This study was supported by funds from the Hacettepe University Medical Faculty, ... Ankara, Turkey; phone: +90 312 3051780; fax: +90 312 3052302; e-mail: byavuz_md@yahoo.com. INTRODUCTION. Hyperlipidemia can ...
Simvastatin Treatment Improves Endothelial Function and Increases Fibrinolysis in Patients with Hypercholestrolemia Gulay S. Guven, MD; Enver Atalar, MD; Bunyamin Yavuz, MD; Yavuz Beyazit, MD; Murat Kekilli, MD; Alparslan Kilicarslan, MD; Levent Sahiner, MD; Gul Oz, MD; Necla Ozer, MD; Serdar Aksoyek, FESC, MD; Ibrahim C. Haznedaroglu, MD; and Tumay Sozen, MD Ankara, Turkey Financial support: This study was supported by funds from the Hacettepe University Medical Faculty, Departments of Internal Medicine and Cardiology. Objectives: Statins reduce cardiovascular events by cholesterol-lowering as well as nonlipid-related actions. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently identified independent risk factor of thrombosis. Endothelial dysfunction is also a strong predictor of cardiovascular events. The aim of this study was to assess the effects of simvastatin treatment on circulating TAFI concentrations and endothelial function in patients with hypercholesterolemia. Methods: Thirty-five patients (19 female, mean age 48 ± 7 years) with hyperlipidemia were recruited into the study. Simvastatin was administered, 40 mg daily, for eight weeks to all subjects. Study subjects did not receive any medication except for lipid-lowering therapy during the follow-up period. Endothelial function was evaluated by flow-mediated dilation (FMD) from the brachial artery of the patients. Plasma lipid parameters, TAFI levels and endothelial function were measured before and after simvastatin treatment. Results: Treatment with simvastatin showed a significant decrement in plasma total cholesterol, LDL cholesterol and triglyceride levels (p30kg/m2) and treatment with antiinflammatory or anticoagulant drugs. Eligible subjects underwent a comprehensive medical assessment, including documentation of the detailed history, physical examination, anthropometric assessment and measurement ofthe essential lab-

oratory variables. All of the subjects were given simvastatin, 40 mg daily, for eight weeks. Study patients did not receive any medication except for lipid-lowering therapy during the follow-up period. The local ethics committee approved the study, and all patients granted written informed consent. Venous blood samples were obtained by the venipuncture of the large antecubital veins of the studied patients without stasis, after a 12-hour fast. The samples were then centrifuged immediately; the plasma was separated and stored at -80°C until the measurement of TAFI. TAFI levels were quantified by the ELISA method via using a commercially available assay (ImunocloneO). Fasting plasma total cholesterol, high-density-lipoprotein (HDL) cholesterol, LDL cholesterol, triglyceride, fibrinogen, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), creatinine, TAFI and other biochemical parameters were measured before and after eight weeks of simvastatin treatment.

Determination of Flow-Mediated Dilation Endothelial dysfunction was measured by flowmediated dilation (FMD) before simvastatin treatment and after eight weeks of treatment. The brachial artery was imaged with a System Five (GE Vingmed Ultrasound, Horten, Norway) cardiac ultrasound scanner and 7.5-mHz linear-array transducer. A pressure cuff was placed on the forearm

Table 1. Clinical characteristics and laboratory parameters of study patients before and after simvastatin therapy

Baseline

After 8 Weeks of Simvastatin

Therapy

P Value

Anthropometric Measurements Weight (kg) Body mass index (kg/m2) Waist circumference (cm)

76.75 ± 11.66 28.16 ± 4.02 92.65 ± 9.98

76.34 ± 11.89 28.00 ± 4.08 92.25 ± 10.29

NS NS NS

Blood Pressure (BP) Systolic BP (mmHg) Diastolic BP (mmHg)

129.71 ± 12.72 87.80 ± 8.24

127.43 ± 10.74 86.29 ± 7.39

NS NS

Metabolic Profiles Fasting plasma glucose (mg/dl) Triglyceride (mg/dl) Total cholesterol (mg/dl) LDL cholesterol (mg/dl) HDL cholesterol (mg/dl) VLDL cholesterol (mg/dl) ALT (IU) AST (IU) Fibrinogen (mg/dl) Creatinine (mg/dl) CK (U/L)

95.23 ± 13.78 174.57 ± 69.08 257.29 ± 22.06 166.71 ± 22.66 55.40 ± 14.34 34.73 ± 13.77 26.57 ± 13.96 22.71 ± 5.67 349.26 ± 61.20 0.9 ± 0.1 45 ± 12

91.54 ± 10.53 137.51 ± 69.47 177.89 ± 26.20 95.57 ± 25.39 55.91 ± 14.96 27.03 ± 13.90 24.34 ± 11.81 23.11 ± 6.31 313.06 ± 61.28 0.8 ± 0.2 44 ± 21

NS 0.008