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Comparative Effects of Atorvastatin, Simvastatin, and Fenofibrate on Serum Homocysteine Levels in Patients with Primary Hyperlipidemia

From the Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece (Dr. Milionis, Dr. Papakostas, Dr. Kakafika, Dr. Elisaf) and the Laboratory of Biochemistry, University Hospital of Ioannina, Ioannina, Greece (Dr. Chasiotis, Dr. Seferiadis).

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 ± 12.5 vs. 50.7 ± 12.6 vs. 51.2 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 ± 1.6 vs. 4.9 ± 1.4 vs. 4.8 ± 1.4 mg/dL, p< 0.0001 for atorvastatin; 5.6 ± 1.6 vs. 4.3 ± 1.4 vs. 4.4 ± 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 ± 3.3 vs. 14.1 ± 3.8 vs. 14.2 ± 3.6 µU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their "cardioprotective" properties.

Key Words: Atorvastatin • fenofibrate • folic acid • homocysteine • lipids • simvastatin • uric acid • vitamin B12

Address for reprints: Moses Elisaf, MD, FRSH, FACA, Department of Internal Medicine, Medical School, University of Ioannina, 451 10 Ioannina, Greece.

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