The Effects of Folic Acid and Atorvastatin Treatment on Homocysteine and Lipid Levels in Hyperlipidemic Patients

Year 2006, Volume: 11 Issue: 2, 108 - 112, 01.04.2006

Süleyman Serdar Koca Yusuf Özkan

Abstract

Objectives: Hyperlipidemia is conventional risk factors of atherosclerosis. In addition, hyperhomocysteinemia was also shown to lead to accelerated atherosclerosis. One of the leading causes of the increase in homocysteine levels is insufficient folic acid intake. Folic acid administration was demonstrated to protective effects on atherosclerosis. In the present study we aimed to investigate the effects of atorvastatin and folic acid administration on lipid profile and homocystein in the treatment of hyperlipidemia, an atherosclerosis risk factor. Materials and Methods: The study included 60 combined hyperlipidemic patients. The patients were randomly allocated to three groups. Only atorvastatin to first group, only folic acid to second group and atorvastatin and folic acid to third group were administered. The study lasted 12 weeks. Lipids and homocysteine levels were studied at the beginning and in the 4th and 12th weeks. Results: It was seen that the group that was administered atorvastatin only had significant changes in the lipids, but not in homocysteine level. The group that received folic acid only was found to have no change in the lipid profile, but had a significant decrease in homocysteine levels. The group that was administered both atorvastatin and folic acid was observed to undergo significant changes in both. Conclusion: Addition of folic acid to atorvastation treatment significantly reduced homocysteine levels, but wasn't observed to have an additional effect on lipids. Evaluation of homocysteine levels in individuals have atherosclerosis risk factors like hyperlipidemia and administration of treatment if the levels are found high, will confer extra benefits in atherosclerosis. ©2006, Fırat Üniversitesi, Tıp Fakültesi

Keywords

-

Hiperlipidemik Hastalarda Folik Asit ve Atorvastatin Tedavisinin Homosistein ve Lipit Düzeylerine Etkisi

Abstract

Amaç: Hiperlipidemi; aterosklerozun konvansiyonel risk faktörlerindendir. Bununla birlikte hiperhomosisteineminin de hızlanmış ateroskleroza yol açtığı ortaya konulmuştur. Homosistein artışının en önemli sebeplerinden birisi ise folik asit alım yetersizliğidir. Oral folik asit uygulamasının ateroskleroz üzerine protektif etkileri gösterilmiştir. Bu çalışmada ateroskleroz risk faktörlerinden olan hiperlipideminin tedavisinde atorvastatin ve folik asit uygulanmasının lipit profili ve homosistein üzerine etkilerini incelemek amaçlandı. Gereç ve Yöntem: Çalışmaya 60 kombine hiperlipidemik hasta alındı. Hastalar üç gruba randomize edildi. Birinci gruba sadece atorvastatin, ikinci gruba sadece folik asit, üçüncü gruba atorvastatin ve folik asit oral verildi. Çalışma 12 hafta sürdü. Tüm hastalarda çalışma başlangıcında, çalışmanın 4. ve 12. haftalarında lipit profili ve plazma homosistein düzeyleri çalışıldı. Bulgular: Sadece atorvastatin alan grupta lipid profilinde anlamlı değişiklikler gözlenmesine karşın, homosistein düzeyinde değişiklik gözlenmedi. Sadece folik asit alan grupta ise lipid profilinde değişiklik gözlenmez iken homosistein düzeyleri anlamlı geriledi. Atorvastatin ve folik asit alan grupta ise hem lipid profili hem de homosistein düzeylerinde anlamlı değişiklikler gözlendi. Sonuç: Atorvastatin tedavisine folik asit ilave edilmesi homosistein düzeyini anlamlı geriletmiş olmasına karşın lipit profili üzerine ilave etkisi gözlenmemiştir. Hiperlipidemi gibi ateroskleroz risk faktörlerinden birisini taşıyan bireylerde homosistein düzeylerinin değerlendirilmesi ve yüksek ise tedavisi ateroskleroz üzerine ilave yararlar sağlayacaktır. ©2006, Fırat Üniversitesi, Tıp Fakültesi

Keywords

Hiperlipidemi, homosistein, folik asit, atorvastatin

References

• Ford ES, Giles WH, Mokdad AH. The distribution of 10-Year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol. 2004; 43: 1791-1796.
• Tokgözoğulu L, Özer N. Ateroskleroz patogenezi. Özcan N. Koroner kalp hastalıkları. 1. Baskı. Ankara 1997.129-163.
• Rosenson RS. Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis. 2004;173:1-12.
• Kwak BR, Mulhaupt F, Mach F. Atherosclerosis: anti- inflammatory and immunomodulatory activities of statins. Autoimmun Rev. 2003; 2: 332-338.
• Bostom AG, Silbershatz H, Rosenberg IH, Selhup J. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999; 24: 1077-1080.
• Robinson K, Arheart K, Refsum H. Low circulating folate and vitamin B6 concentrations risk factors for stroke, peripheral vascular disease, and coronary artery disease. Circulation. 1998; 97: 437-443.
• Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997; 277: 1775-1781.
• Herman W, Schorr H, Purschwitz K, Rassoul F, Richter V. Total homocycteine vitamin B12, and total antioxidant status in vegetarians. Clinical Chemistry 2001; 47: 1094-101.
• Dalery K, Luier S, Selhup J, Latour Y. Homocysteine and Coronary Artery Disease in French Canadian Subject: Relation With Vitamins B12, B6, Prydoxal Phosphate, and folat. Am J Cardiol. 1995; 75: 1107-1011.
• Audelin MC, Genest J Jr. Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis 2001; 159: 497- 511.
• Hoogeveen EK, Kostense PJ, Beks PJ, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998; 18: 133-138.
• Aksoy M, Akdemir İ, Aksoy ŞN, et al. Homosistein düzeyi yüksek olan koroner arter hastalarında, tedavi ile plazma homosistein düzeyinde sağlanan düşmenin vasküler endotel fonksiyonu ve miyokardın iskemi yükü üzerine etkisi. Türk Kardiol Dern Arş. 2000; 28: 598-606.
• Peter N. Herbert, MD. Aminoasit metabolizması bozuklukları. Çalangu S, Siva A, Tuzcu M. Cecil essential, at medicine, İstanbul, Türkiye, Nobel Tıp Kitapları A.Ş. 2000; 470-472.
• Frohlich JJ. Lipoproteins and homocysteine as risk factors for atherosclerosis: assessment and treatment. Can J Cardiol 1995; 11: 18C-23C.
• Lindeman RD, Romero LJ, Yau CL, et al. Serum homocysteine concentrations and their relation to serum folate and vitamin B12 concentrations and coronary artery disease prevalence in an urban, bi-ethnic community. Ethn Dis. 2003; 13: 178-185.
• Lekakis JP, Papamichael CM, Papaioannou TG, et al. M. Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins. Eur J Cardiovasc Prev Rehabil. 2004; 11: 416-420.
• Verhaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial. Circulation 1999; 100: 335-338.
• Dalery K, Luier S, Selhup J, Latour Y. Homocysteine and Coronary Artery Disease in French Canadian Subject: Relation With Vitamins B12, B6, Prydoxal Phosphate, and folat. Am J Cardiol. 1995; 75: 1107-1111.
• Clarke R, Daly L, Robinson K. Hyperhomocysteinemia: An independent risk factor for vascular disease. N Engl J Med. 1991; 324: 1149-1155.
• Sasaki S, Kuhawara N, Kunitomo K. Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution and remnant lipoprotein in patients with mixed hyperlipoproteinemia. AMJ Cardiol. 2002; 89: 386-389.
• Melenovsky V, Malik J, Wichterle D. Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. AHJ. 2002; 144: E6
• Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Expert Opin Drug Saf. 2004; 3: 101-11.
• Jankowski P, Kawecka-Jaszcz K. Lipid-lowering drugs and homocysteine. A comparison between statins and other lipid- lowering drugs. Atherosclerosis. 2004; 172: 191-194.
• Giral P, Bruckert E, Jacob N, et al. Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Atherosclerosis. 2001; 154: 421-427.
• Malik J, Melenovsky V, Wichterle D, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT). Cardiovasc Res. 2001; 52: 290-298.
• Miltiadous G, Papakostas J, Chasiotis G, Seferiadis K, Elisaf M. Statins and homocysteine. Atherosclerosis. 2003; 166: 199-200.
• Haak E, Abletshauser C, Weber S, et al. Fluvastatin therapy improves microcirculation in patients with hyperlipidaemia. Atherosclerosis 2001; 155: 395-401.
• Rizos E, Bairaktari E, Kostoula A, et al. The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study. J Cardiovasc Pharmacol Ther. 2003; 8: 127-134.
• Luftjohann D, Sigit JI, Locatelli S, von Bergmann K, Schmidt HH. High-dose simvastin (80 mg/day) decreases plasma concentrations of total homocyst(e)ine in patients with hypercholesteromia. Atherosclerosis 2001; 155: 265-266.
• Ridker PM, Shih J, Cook TJ, et al. Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events. Circulation 2002; 105: 1776-1779.
• Woo CW, Siow YL, Pierce GN, et al. Hyperhomocysteinemia Induces Hepatic Cholesterol Biosynthesis and Lipid Accumulation via Activation of Transcription Factors. Am J Physiol Endocrinol Metab. 2005; 288: E1002-10. Epub 2005
• Giltay EJ, Hoogeveen EK, Elbers JM, et al. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis 1998; 139: 197-198.
• Gao W, Jiang N, Meng Z, Tang J. Hyperhomocysteinemia in coronary heart disease. Chin Med J (Engl). 1999; 112: 586-589.
• Veerkamp MJ, de Graaf J, den Heijer M, Blom HJ, Stalenhoef AF. Plasma homocysteine in subjects with familial combined hyperlipidemia. Atherosclerosis 2003; 166: 111-117.
• Venn BJ, Mann JI, Williams SM. Assesment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial. Eur J Clin. 2002; 56: 748-754.
• Mayer O Jr, Simon J, Rosolova H. The effects of folate supplementation on some coagulation parameters and oxidative status surrogates. Eur J Clin Pharmacol. 2002; 58: 1-5
• Mark L, Erdei F, Marki-Zay J, Nagy E. Plasma homocysteine levels in patients with ischemic heart disease. Orv Hetil. 2001; 142: 1611-1615.
• Liem AH, van Boven AJ, Veeger NJ, et al. Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial. Int J Cardiol. 2004; 93: 175-179.
• Verhaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial. Circulation. 1999; 100: 335-338.
• Usui M, Matsuoka H, Miyazaki H, et al. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci (Lond). 1999; 96: 235-239.
• Van den Berg M, Boers GH, Franken DG, et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest. 1995; 25: 176-181.
• Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002; 22: 6-13.
• Kabul Tarihi: 28.02.2006