Skip to main content
PMC home page
Journal of the National Medical Association logoLink to Journal of the National Medical Association
. 2006 Aug;98(8):1273–1277.

Effects of atorvastatin on coagulation parameters and homocysteine in patients with primary hypercholesterolemia.

Zahit Bolaman 1, Gurhan Kadikoylu 1, Nihat Ozgel 1, Cigdem Yenisey 1
PMCID: PMC2569568  PMID: 16916124

Abstract

BACKGROUND: The mechanism of the antithrombotic action of statins is unclear. We evaluated the effects of atorvastatin on the coagulation parameters and homocysteine levels of patients with primary hypercholesterolemia. MATERIALS AND METHODS: Forty-four patients with primary hypercholesterolemia were treated with atorvastatin 10 mg/d for 24 weeks at Adnan Menderes University Medical Faculty, Division of Hematology, Aydin, Turkey. We evaluated the effects of atorvastatin on homocysteine; lipid parameters such as total cholesterol, low-density-lipoprotein (LDL) cholesterol, very-low-density-lipoprotein (VLDL) cholesterol, triglycerides, high-density-lipoprotein (HDL) cholesterol, lipoprotein (a), apolipoprotein Al and apolipoprotein B; and coagulation parameters such as fibrinogen, antithrombin-III, protein C, protein S, von Willebrand factor, D-dimer, partial thromboplastin time and prothrombin time; and hematological parameters such as hemoglobin, white blood cell and platelet counts, vitamin B12 and folic acid. RESULTS: Atorvastatin significantly decreased the levels of total cholesterol, LDL cholesterol (p < 0.001), VLDL cholesterol, triglycerides and apo B (p < 0.001). The level of HDL cholesterol significantly increased with atorvastatin treatment (p < 0.001). Atorvastatin significantly increased the levels of fibrinogen (p < 0.001), but it had no effect on other coagulation factors and homocysteine (p > 0.05). After treatment, while vitamin B12 levels significantly increased (p < 0.05), other hematological parameters were not changed with atorvastatin (p > 0.05). CONCLUSION: Although there were beneficial effects of atorvastatin on lipid parameters, atorvastatin did not significantly change the level of homocysteine and hematological, and coagulation parameters, with the exception of fibrinogen and vitamin B12 levels.

Full text

PDF
1273

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alaupovic P., Heinonen T., Shurzinske L., Black D. M. Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. Atherosclerosis. 1997 Aug;133(1):123–133. doi: 10.1016/s0021-9150(97)00119-6. [DOI] [PubMed] [Google Scholar]
  2. Bickel Christoph, Rupprecht Hans J., Blankenberg Stefan, Espinola-Klein Christine, Rippin Gerd, Hafner Gerd, Lotz Johannes, Prellwitz Winfried, Meyer Jürgen, AtheroGene Group Influence of HMG-CoA reductase inhibitors on markers of coagulation, systemic inflammation and soluble cell adhesion. Int J Cardiol. 2002 Jan;82(1):25–31. doi: 10.1016/s0167-5273(01)00576-9. [DOI] [PubMed] [Google Scholar]
  3. Broncel Marlena, Marczyk Iwona, Chojnowska-Jezierska Julita, Michalska Marta, Sikora Joanna, Kostka Barbara. Porównanie wpływu simwastatyny i atorwastatyny na wybrane parametry układu krzepniecia u chorych z hiperlipidemia typu II. Pol Merkur Lekarski. 2005 Apr;18(106):380–384. [PubMed] [Google Scholar]
  4. Castelli W. P. Epidemiology of coronary heart disease: the Framingham study. Am J Med. 1984 Feb 27;76(2A):4–12. doi: 10.1016/0002-9343(84)90952-5. [DOI] [PubMed] [Google Scholar]
  5. Colli S., Eligini S., Lalli M., Camera M., Paoletti R., Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol. 1997 Feb;17(2):265–272. doi: 10.1161/01.atv.17.2.265. [DOI] [PubMed] [Google Scholar]
  6. Crouse J. R., 3rd, Frohlich J., Ose L., Mercuri M., Tobert J. A. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol. 1999 May 15;83(10):1476-7, A7. doi: 10.1016/s0002-9149(99)00153-8. [DOI] [PubMed] [Google Scholar]
  7. Dujovne C. A., Harris W. S., Altman R., Overhiser R. W., Black D. M. Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients. Am J Cardiol. 2000 Feb 1;85(3):350–353. doi: 10.1016/s0002-9149(99)00745-6. [DOI] [PubMed] [Google Scholar]
  8. Edgington T. S., Mackman N., Brand K., Ruf W. The structural biology of expression and function of tissue factor. Thromb Haemost. 1991 Jul 12;66(1):67–79. [PubMed] [Google Scholar]
  9. Eikelboom J. W., Lonn E., Genest J., Jr, Hankey G., Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999 Sep 7;131(5):363–375. doi: 10.7326/0003-4819-131-5-199909070-00008. [DOI] [PubMed] [Google Scholar]
  10. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486–2497. doi: 10.1001/jama.285.19.2486. [DOI] [PubMed] [Google Scholar]
  11. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
  12. Girolami A., Simioni P., Scarano L., Girolami B. Venous and arterial thrombophilia. Haematologica. 1997 Jan-Feb;82(1):96–100. [PubMed] [Google Scholar]
  13. Joukhadar C., Klein N., Prinz M., Schrolnberger C., Vukovich T., Wolzt M., Schmetterer L., Dorner G. T. Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. Thromb Haemost. 2001 Jan;85(1):47–51. [PubMed] [Google Scholar]
  14. Kadikoylu Gurhan, Yukselen Vahit, Yavasoglu Irfan, Bolaman Zahit. Hemostatic effects of atorvastatin versus simvastatin. Ann Pharmacother. 2003 Apr;37(4):478–484. doi: 10.1345/aph.1C189. [DOI] [PubMed] [Google Scholar]
  15. Koschinsky Marlys L. Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action of an enigmatic lipoprotein. Curr Atheroscler Rep. 2005 Sep;7(5):389–395. doi: 10.1007/s11883-005-0052-y. [DOI] [PubMed] [Google Scholar]
  16. Kushiya Fumihiko, Wada Hideo, Ooi Kinue, Sakurai Yuko, Sakaguchi Akane, Noda Maki, Abe Yasunori, Nakasaki Takahiro, Tsukada Tetsuya, Shiku Hiroshi. Effects of atorvastatin on serum lipids, lipoproteins, and hemostasis. Am J Hematol. 2005 Jan;78(1):1–6. doi: 10.1002/ajh.20191. [DOI] [PubMed] [Google Scholar]
  17. Leibovitz Eyal, Hazanov Neli, Frieman Angela, Elly Itzhak, Gavish Dov. Atorvastatin reduces fibrinogen levels in patients with severe hypercholesterolemia: additional evidence to support the anti-inflammatory effects of statins. Isr Med Assoc J. 2004 Aug;6(8):456–459. [PubMed] [Google Scholar]
  18. Makris M. Hyperhomocysteinemia and thrombosis. Clin Lab Haematol. 2000 Jun;22(3):133–143. doi: 10.1046/j.1365-2257.2000.00301.x. [DOI] [PubMed] [Google Scholar]
  19. Marais A. D., Firth J. C., Bateman M. E., Byrnes P., Martens C., Mountney J. Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997 Aug;17(8):1527–1531. doi: 10.1161/01.atv.17.8.1527. [DOI] [PubMed] [Google Scholar]
  20. Maresca G., Di Blasio A., Marchioli R., Di Minno G. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1368–1377. doi: 10.1161/01.atv.19.6.1368. [DOI] [PubMed] [Google Scholar]
  21. Mayer J., Eller T., Brauer P., Solleder E. M., Schäfer R. M., Keller F., Kochsiek K. Effects of long-term treatment with lovastatin on the clotting system and blood platelets. Ann Hematol. 1992 Apr;64(4):196–201. doi: 10.1007/BF01696223. [DOI] [PubMed] [Google Scholar]
  22. McKinley M. C. Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease. Proc Nutr Soc. 2000 May;59(2):221–237. doi: 10.1017/s0029665100000252. [DOI] [PubMed] [Google Scholar]
  23. Melenovsky Vojtech, Malik Jan, Wichterle Dan, Simek Jan, Pisarikova Alexandra, Skrha Jan, Poledne Rudolf, Stavek Petr, Ceska Richard. Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. Am Heart J. 2002 Oct;144(4):E6–E6. doi: 10.1016/s0002-8703(02)00142-4. [DOI] [PubMed] [Google Scholar]
  24. Milionis Haralampos J., Papakostas John, Kakafika Anna, Chasiotis George, Seferiadis Konstantine, Elisaf Moses S. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. J Clin Pharmacol. 2003 Aug;43(8):825–830. doi: 10.1177/0091270003255920. [DOI] [PubMed] [Google Scholar]
  25. Mitropoulos K. A., Armitage J. M., Collins R., Meade T. W., Reeves B. E., Wallendszus K. R., Wilson S. S., Lawson A., Peto R. Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group. Eur Heart J. 1997 Feb;18(2):235–241. doi: 10.1093/oxfordjournals.eurheartj.a015225. [DOI] [PubMed] [Google Scholar]
  26. Nygård O., Nordrehaug J. E., Refsum H., Ueland P. M., Farstad M., Vollset S. E. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997 Jul 24;337(4):230–236. doi: 10.1056/NEJM199707243370403. [DOI] [PubMed] [Google Scholar]
  27. Pokrovskaia E. V., Gratsianskii N. A., Vaulin N. A., Deev A. D. Sviaz' izmenenii urovnei lipidov i markerov vospaleniia i gemostaza, proizoshedshikh vo vremia priema statinov, u bol'nykh s ostrym koronarnym sindromom bez pod"ema segmenta ST na EKG. Kardiologiia. 2004;44(7):40–45. [PubMed] [Google Scholar]
  28. Ruggeri Zaverio M. Von Willebrand factor. Curr Opin Hematol. 2003 Mar;10(2):142–149. doi: 10.1097/00062752-200303000-00008. [DOI] [PubMed] [Google Scholar]
  29. Sasaki Susumu, Kuwahara Noriko, Kunitomo Keiko, Harada Sanae, Yamada Takashi, Azuma Akihiro, Takeda Kazuo, Nakagawa Masao. Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia. Am J Cardiol. 2002 Feb 15;89(4):386–389. doi: 10.1016/s0002-9149(01)02257-3. [DOI] [PubMed] [Google Scholar]
  30. Shepherd J., Cobbe S. M., Ford I., Isles C. G., Lorimer A. R., MacFarlane P. W., McKillop J. H., Packard C. J. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995 Nov 16;333(20):1301–1307. doi: 10.1056/NEJM199511163332001. [DOI] [PubMed] [Google Scholar]
  31. Sotiriou C. G., Cheng J. W. Beneficial effects of statins in coronary artery disease--beyond lowering cholesterol. Ann Pharmacother. 2000 Dec;34(12):1432–1439. doi: 10.1345/aph.10124. [DOI] [PubMed] [Google Scholar]
  32. Tousoulis D., Antoniades C., Bosinakou E., Kotsopoulou M., Tsioufis C., Tentolouris C., Trikas A., Pitsavos C., Stefanadis C. Effects of atorvastatin on reactive hyperaemia and the thrombosis-fibrinolysis system in patients with heart failure. Heart. 2005 Jan;91(1):27–31. doi: 10.1136/hrt.2003.027110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wada H., Mori Y., Kaneko T., Wakita Y., Minamikawa K., Ohiwa M., Tamaki S., Yokoyama N., Kobayashi T., Deguchi K. Hypercoagulable state in patients with hypercholesterolemia: effects of pravastatin. Clin Ther. 1992 Nov-Dec;14(6):829–834. [PubMed] [Google Scholar]
  34. White C. M. Pharmacological effects of HMG CoA reductase inhibitors other than lipoprotein modulation. J Clin Pharmacol. 1999 Feb;39(2):111–118. doi: 10.1177/00912709922007642. [DOI] [PubMed] [Google Scholar]
  35. Whiteman T., Hassouna H. I. Hypercoagulable states. Hematol Oncol Clin North Am. 2000 Apr;14(2):355-77, viii. doi: 10.1016/s0889-8588(05)70138-6. [DOI] [PubMed] [Google Scholar]
  36. Wierzbicki A. S., Lumb P. J., Semra Y., Chik G., Christ E. R., Crook M. A. Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias. QJM. 1999 Jul;92(7):387–394. doi: 10.1093/qjmed/92.7.387. [DOI] [PubMed] [Google Scholar]
  37. Young I. S., Woodside J. V. Folate and homocysteine. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):427–432. doi: 10.1097/00075197-200011000-00003. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the National Medical Association are provided here courtesy of National Medical Association

RESOURCES