Comparison of Effects of Atorvastatin and Fenofibrate on Plasma Homocysteine, Folic Acid and Vitamin B12 Levels in Patients With Mixed Hyperlipidemia

Yıl 2006, Cilt: 11 Sayı: 1, 16 - 20, 01.02.2006

Yılmaz Özbay Mehmet Akbulut Emir Dönder Adil Baydaş Gıyasettin Baydas M.ferit Gürsu

Öz

Objectives: Hyperhomocysteinemia is an independent cardiovascular risk factor. Lipid lowering agents such as fenofibrate have been reported to elevate plasma homocysteine levels. Atorvastatin is another kind of lipid lowering agent and there is not enough study investigating its effects on plasma homocysteine. In the present study we aimed to compare the effects of atorvastatin and fenofibrate on plasma homocysteine, folic acid and vitamin B12 levels. Materials and Methods: Total of 43 patients were randomized into one of 2 groups: One of them (n=20) treated with atorvastatin, other (n=23) with fenofibrate for 3 months. After 1 and 3 months of treatment with these drugs, blood samples were collected and plasma lipids, folic acid, vitamin B12 and homocysteine levels were determined. Results: Both of the lipid lowering agents significantly decreased plasma lipid levels. Atorvastatin group showed a significant reduction in total cholesterol and LDL-C than those in fenofibrate group. On the other hand, fenofibrate caused a greater reduction in triglyceride levels compared to the atorvastatin. There was no change in plasma folic acid and vitamin B12 levels after treatment with both of these hypolipidemic drugs. There was a significant increase in homocysteine levels after treatment with fenofibrate and atorvastatin, although fenofibrate was more effective than atorvastatin (36 and 15% respectively). Conclusions: We conclude that increases in plasma homocysteine levels are a result of the known impairment of renal function caused by fenofibrate and a result of impairment of liver function caused by atorvastatin.©2006, Fırat Üniversitesi, Tıp Fakültesi

Anahtar Kelimeler

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Hiperlipidemik hastalarda atorvastatin ve fenofibratın plazma homosistein, folik asit ve B12 vitamin düzeylerine etkilerinin karşılaştırılması

Öz

Amaç: Hiperhomosisteinemi bağımsız bir kardiyovasküler risk faktörüdür. Fenofibrat gibi lipit düşürücü ilaçların plazma homosistein miktarını arttırdığı bildirilmiştir. Atorvastatin diğer bir tip lipit düşürücü olup plazma homosistein üzerindeki etkileri yeterince çalışılmamıştır. Bu çalışmada atorvastatin ve fenofibratın plazma homosistein, folik asit ve B12 vitamin değerlerine olan etkilerini karşılaştırmayı amaçladık. Gereç ve yöntem: Toplam 43 hiperlipidemik hasta iki gruba ayrıldı. Bir grup (n=20) atorvastatin ile, diğeri (n=23) fenofibrat ile 3 ay tedavi edildi. Tedavinin 1. ve 3. aylarında kan örnekleri alındı ve plazma lipitleri, folik asit, B12 vitamini ve homosistein düzeyleri ölçüldü. Bulgular: Her iki lipid düşürücü ilaç plazma lipit düzeylerini önemli oranda düşürdü. Atorvastatin grubunda total kolesterol ve LDL-C miktarları fenofibrat grubundan daha fazla düşüş gösterdi. Diğer taraftan fenofibrat atorvastatinle karşılaştırıldığında trigliserid düzeyinde daha belirgin düşüşe neden oldu. Her iki lipit düşürücü ilaç tedavisinden sonra folik asit ve B12 vitamin miktarlarında herhangi bir değişiklik gözlenmedi. Homosistein düzeyleri hem fenofibrat hem de atorvastatin tedavisinden sonra artış göstermekle beraber fenofibrat atorvastatinden daha etkili bulundu (sırasıyla, %36 ve %15). Sonuç: Sonuç olarak plazma homosistein miktarındaki artışın fenofibratın neden olduğu renal fonksiyon bozukluğundan ve atorvastatinin neden olduğu muhtemel karaciğer fonksiyon bozukluğundan ileri geldiğini düşünmekteyiz. ©2006, Fırat Üniversitesi, Tıp Fakültesi

Anahtar Kelimeler

Atorvastatin, fenofibrat, homosistein, folik asit, B12 vitamini

Kaynakça

• Nehler MR, Taylor LM, Porter JM. Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Surg. 1997; 5:559-567
• Bostom AG, Silbershatz H, Rosenberg IH et al. No fasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999; 159:1077-1080
• Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337:230-236
• Tsai MY, Garg U, Key NS, Hanson NQ, Suh A, Schwichtenberg K. Molecular and biochemical approaches in the identification of heterozygote for homocysteinuria. Atherosclerosis 1996; 122: 69- 77
• Bunout D, Garrido A, Suazo M, Kauffman R, Venegas P, de la Maza P, and et al. Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients. Nutrition 2000; 16:107-110
• Olszewski AJ, McCully KS. Fish oil decreases serum homocysteine in hyperlipemic men. Coron Artery Dis 1993; 4:53- 60
• Baydas G, Gursu MF, Cikim G, Canatan H. Homocysteine levels are increased due to lack of melatonin in pinealectomized rats: is there a link between melatonin and homocysteine? J Pineal Res. 2002; 32: 63-64
• Gursu MF, Baydas G, Cıkım G, Canatan H. Insulin increases homocysteine levels in a dose-dependent manner in diabetic rats. Arch Med Res. 2002; 33:305-7.
• Ashfield-Watt PA, Moat SJ, Doshi SN, McDowell IF. Folate, homocysteine, endothelial function and cardiovascular disease. What is the link? Biomed Pharmacother 2001; 55:425-33
• Van Guldener C, Stehouwer CD. Homocysteine-lowering treatment: an overview. Expert Opin Pharmacother 2001; 2:1449- 60.
• La Rosa JC. Prevention and treatment of coronary heart disease: who benefits? Circulation 2001; 104: 1688-1692
• Foody JM, Nissen SE. Effectiveness of statins in acute coronary syndromes. Am J Cardiol 2001; 88 (4 Suppl):31F-35F
• Waters DD. Are we aggressive enough in lowering cholesterol? Am J Cardiol 2001; 88 (4 Suppl): 10F-15F
• Olsson AG, Pears J, McKellar J, Mizan J, Raza A. Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Am J Cardiol 2001; 88:504-508
• De Lorgeril M, Salen P, Paillard F, Lacan P, Richard G. Lipid- lowering drugs and homocysteine. Lancet 1999 ; 353:209-210
• Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999; 354: 219-220
• Jonkers IJ, de Man FH, Onkenhout W, van der Laarse A, Smelt AH. Implication of fibrate therapy for homocysteine. Lancet 1999; 354:1208
• Stulc T, Melenovsky V, Grauova B, Kozich V, Ceska R. Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy. Nutrition 2001; 17:721-723
• Giral P, Giral E, Jacob N, Chapman MJ, Foglietti MJ, Turpin G. Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Atherosclerosis 2001; 154:421-427
• 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
• Ray SK, Rege NN. Atorvastatin: in the management of hyperlipidaemia. J Postgrad Med 2000; 46:242-3
• Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol 1999;10:561-574
• Lipscombe J, Lewis GF, Cattran D, Bargman JM Deterioration in renal function associated with fibrate therapy. Clin Nephrol 2001; 55:39-44
• Tsimihodimos V, Kakafika A, Elisaf M. Fibrate treatment can increase serum Creatinin levels. Nephrol Dial Transplant 2001;16:1301
• Stead LM, Brosnan ME, Brosnan JT. Characterization of homocysteine metabolism in the rat liver. Biochem J 2000; 3:685-692
• Bosy-Westphal A, Petersen S, Hinrichsen H, Czech N, J Muller M. Increased plasma homocysteine in liver cirrhosis. Hepatol Res 2001; 20:28-38
• Kabul Tarihi: 25.12.2005