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Statinlerin Nöroloji Pratiğindeki Yeri

Year 2009, Volume: 26 Issue: 2, 55 - 61, 06.12.2010

Abstract

Statinler, 3-hidroksi–3-metilglutaril koenzim A (HMG-CoA) redüktaz inhibisyonu sayesinde karaciğerde hücre içerisinde LDL-kolesterol seviyesinde azalma sağlarlar. Bu durum karaciğer hücre yüzeyindeki LDL reseptör sayısının artmasına, dolayısıyla plazma LDL seviyelerinin düşmesine neden olur. Ayrıca statinler LDL’nin periferden absorbsiyonunu artırarak karaciğer hücrelerine ve diğer hücrelere girişini ve orada yıkımını artırarak kolesterol seviyesini azaltırlar.Statinlerin kolesterol düşürücü etkilerinin yanı sıra inflamasyon ve oksidasyon, hücre proliferasyonu,
endotel fonksiyonları, koagülasyon ve trombosit sistemi üzerine de etkili olduğu gösterilmiştir.Kolesterol artışı ile koroner arter hastalığı arasında ilişki olduğu ve aynı zamanda kolesterol düşürücü tedavinin koroner arter hastalığının önlenmesi ve tedavisindeki önemi değişik çalışmalarla ortaya konmuştur. Benzer mekanizmalarla hiperkolesteroleminin inmede rol oynadığı gösterilmiştir. Bunun dışında multiple skleroz, demans gibi inme dışındaki nörolojik hastalıkların etyolojisinde hiperkolesteroleminin oynadığı rol son zamanlarda araştırılmaya başlanmıştır. Tüm bu çalışmaların sonunda statinlerin nörolojik hastalıklarda kullanımıyla
ilgili daha fazla randomize, kontrollü çalışmaya ihtiyaç olduğu sonucuna varılmıştır.


Role of statins in the practice of clinic neurology

Statins reduce the level of LDL-cholesterol in liver cells by inhibiting 3-hydroxy 3-methylglutaryl coenzyme A (HMG-COA) reductase. This causes an increase of the number
of the LDL receptors located on liver cell surfaces and thus there is a decrease in plasma LDL levels. Statins also cause an increase in the peripheral absorbtion of LDL and more
LDL enters liver cells where it is destructed causing a reduction in cholesterol levels.Besides their cholesterol reducing effects, statins have been assessed as having functions in inflamation and oxidation, cell proliferation, endothelial functions, coagulation and platelet systems.
Various studies have put forward a relationship between cholesterol increase and coronory artery disease. It has also been documented that cholesterol reducing therapy is important in the preventation and cure of coronory artery disease. Using similar mechanisms, it has also been shown that hypercholesterolemia also plays an important role in the evalation of stroke.Recently, studies investigating the role of hypercholesterolemia in the etiologies of neurological
diseases other than stroke such as multiple sclerosis and dementia have been designed also. Results of studies concerning the usage of statins in neurological diseases have led to a conclusion that more randomised and controlled studies are needed.

References

  • Amarenco P., 2001. Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction. Neurology. 57, 35-44.
  • Bales K, Verina T, Cummins D, Du Y, Dodel RC, Saura J, 1999. Apolipoprotein E is essential for amyloid deposition and neurotic degeneration in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci. 96, 15233–15238.
  • Björkhem I, Lütjohann D, Diczfalusy U., 1998. Cholesterol homeostasis in human brain turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J. Lipid Res. 39, 1594–1600.
  • Blauw GJ, Lagaay AM, Smelt AHM, Westendorp RG, 1997. Stroke, statins and cholesterol. A meta analysis of randomized, place- bocontrolled, double-blind trials with HMG-CoA reductase inhibitors. Stroke. 28, 946–950.
  • Cucchiara B, Kasner SE., 2001. Use of statins in CNS disorders. J Neurol Sci. 187, 81–89.
  • Delanty N, Vaughan CJ., 1997. Vascular effects of statins in stroke. Stroke. 28, 2315-2320.
  • Eastern Stroke and Coronary Heart Disease Collaborative Research Group., 1998. Blood pressure, cholesterol, and stroke in eastern Asia. Lancet. 352, 1801–1807.
  • Evans R, Emsley C, Gao S., 2000. Serum cholesterol, APOE genotype and the risk of Alzheimer disease. A population based study of African Americans. Neurology. 54, 240–242.
  • Frears ER, Stephens DJ, Walters CE., 1999. The role of cholesterol depletion in the biosynthesis of βamyloid. Neuroreport. 1699- 1705.
  • Gaw A., 2004. Genel uygulamada statinler. Bölüm 3; Statinler nelerdir ve işlevleri nelerdir. İkinci Baskı., 21-38.
  • Grundy SM., 1998. Statin trials and goals of cholesterol lowering therapy. Circulation 1998. 97, 1436–1439.
  • Hachinski V, Graffagnino C, Beaudry M, , Bernier G, Buck C, Donner A, ve ark., 1996. Lipids and stroke. Arch Neurol. 53, 303– 308.
  • Haley R., 2000. Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease. Arch Neurol. 57, 1410–1412.
  • Hamamcıoğlu K,Vural O., 2005. Statins For The Treatment of Multiple Sclerosis. J.Neurol. Sci.[Turk]. 22, 221–230.
  • Heart Protection Study Collaborative Group., 2004. Effect of cholesterol-lowering with simvastatin on stroke and other major vas- cular events in 20,536 people with cerebrovascular disease or other high-risk conditions. Lancet. 363, 757–767.
  • Iso H, Jacops DR, Wenworth D, , Neaton JD, Cohen JD, 1989. Serum cholesterol levels and six-year mortality from stroke in 350 977 men screened for the multiple risk factor intervention trial. N Engl J Med. 320, 904–910.
  • Kalmijn S, Feskens E, Launer L., 1996. Cerebrovascular disease, he apolipoprotein E4 allele and cognitive decline an a community- based study of elderly men. Stroke. 27, 2230–2235.
  • Kayaalp SO., 1998. Tıbbi Farmakoloji. Hipolipidemik ilaçlar. 1. Cilt, 8. Baskı. Ankara, Hacettepe-Taş Kitapçılık Ltd.Şti. 567- 587.
  • Liao JK., 2002. Beyond lipid lowering: the role of statins in vascular protection. Int. J. Cardiol. 86, 5–18.
  • Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V, ve ark., 1999. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) Study. Circulation. 99, 216–223
  • Prospective studies collaborations., 1995. Cholesterol, diastolic blood pressure, and stroke: 13000 strokes in 450 000 people in 45 prospective cohorts. Lancet. 346, 1647–1653
  • Rosenson RS, Tangey CC.,1998. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 279 20, 1643–1650.
  • Rockwood K, Kirkland S, Hogan DB., 2002. Use of lipid-lowering agents, indication bias, and the risk of dementia in commuity- dwelling elderly people. Arch Neurol. 59, 223–227.
  • Sena A, Pedrosa R, Morais MG., 2003. Therapeutic potential of lovastatin in multiple sclerosis. J. Neurol. 250, 754–755.
  • Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, ve ark., 1995. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 333, 1301–1307.
  • Simons M, Keller P, Dichgans J., 2000. Cholesterol and Alzheimer’s disease: Is there a link. Neurology. 57,1089–1093.
  • SPARCL Investigators. 2006. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355, 549–559.
  • Stanislaus R, Singh AK, Singh I., 2001. Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis. J Neurosci Res. 66,155–162.
  • Sterzer P, Meintzschel F, Rosler A., 2001. Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small vessel disease. Stroke. 32, 2817–2820.
  • Takemoto M, Liao JK., 2001. Pleiotropic effects of 3-hydroxy–3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 21,1712–1719.
  • TenDam VH, Bollen EL, Westendorp RG., Role of statins in prevention of stroke and dementia. Ned Tijdschr Geneeskd. 145,1918– 1921.
  • Warshafsky S, Packard D, Marks SJ, Sachdeva N, Terashita DM, Kaufman G, ve ark., 1999. Efficacy of 3-hydroxy-3- methylglu- taryl coenzyme a reductase inhibitors for prevention of stroke. J Gen Intern Med. 14,763–774.
  • Vaughan CJ, Murphy MB, Buckley BM., 1998. Statins do more than just lower cholesterol. Lancet. 348,1079–1082.
  • Vaughan CJ, Delanty N., 1999. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke. 30, 1969–1973.
  • Vaughan CJ, Delanty N, Basson CT., 2001. Do statins afford neuroprotection in patients with cerebral ischemia and stroke. CNS Drugs. 15, 589-596.
  • Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic-Plese S, ve ark., 2004. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet. 363, 1607–1608
  • Yano K, Reed DM, MacLean CJ., 1989. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke. 20, 4605
Year 2009, Volume: 26 Issue: 2, 55 - 61, 06.12.2010

Abstract

References

  • Amarenco P., 2001. Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction. Neurology. 57, 35-44.
  • Bales K, Verina T, Cummins D, Du Y, Dodel RC, Saura J, 1999. Apolipoprotein E is essential for amyloid deposition and neurotic degeneration in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci. 96, 15233–15238.
  • Björkhem I, Lütjohann D, Diczfalusy U., 1998. Cholesterol homeostasis in human brain turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J. Lipid Res. 39, 1594–1600.
  • Blauw GJ, Lagaay AM, Smelt AHM, Westendorp RG, 1997. Stroke, statins and cholesterol. A meta analysis of randomized, place- bocontrolled, double-blind trials with HMG-CoA reductase inhibitors. Stroke. 28, 946–950.
  • Cucchiara B, Kasner SE., 2001. Use of statins in CNS disorders. J Neurol Sci. 187, 81–89.
  • Delanty N, Vaughan CJ., 1997. Vascular effects of statins in stroke. Stroke. 28, 2315-2320.
  • Eastern Stroke and Coronary Heart Disease Collaborative Research Group., 1998. Blood pressure, cholesterol, and stroke in eastern Asia. Lancet. 352, 1801–1807.
  • Evans R, Emsley C, Gao S., 2000. Serum cholesterol, APOE genotype and the risk of Alzheimer disease. A population based study of African Americans. Neurology. 54, 240–242.
  • Frears ER, Stephens DJ, Walters CE., 1999. The role of cholesterol depletion in the biosynthesis of βamyloid. Neuroreport. 1699- 1705.
  • Gaw A., 2004. Genel uygulamada statinler. Bölüm 3; Statinler nelerdir ve işlevleri nelerdir. İkinci Baskı., 21-38.
  • Grundy SM., 1998. Statin trials and goals of cholesterol lowering therapy. Circulation 1998. 97, 1436–1439.
  • Hachinski V, Graffagnino C, Beaudry M, , Bernier G, Buck C, Donner A, ve ark., 1996. Lipids and stroke. Arch Neurol. 53, 303– 308.
  • Haley R., 2000. Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease. Arch Neurol. 57, 1410–1412.
  • Hamamcıoğlu K,Vural O., 2005. Statins For The Treatment of Multiple Sclerosis. J.Neurol. Sci.[Turk]. 22, 221–230.
  • Heart Protection Study Collaborative Group., 2004. Effect of cholesterol-lowering with simvastatin on stroke and other major vas- cular events in 20,536 people with cerebrovascular disease or other high-risk conditions. Lancet. 363, 757–767.
  • Iso H, Jacops DR, Wenworth D, , Neaton JD, Cohen JD, 1989. Serum cholesterol levels and six-year mortality from stroke in 350 977 men screened for the multiple risk factor intervention trial. N Engl J Med. 320, 904–910.
  • Kalmijn S, Feskens E, Launer L., 1996. Cerebrovascular disease, he apolipoprotein E4 allele and cognitive decline an a community- based study of elderly men. Stroke. 27, 2230–2235.
  • Kayaalp SO., 1998. Tıbbi Farmakoloji. Hipolipidemik ilaçlar. 1. Cilt, 8. Baskı. Ankara, Hacettepe-Taş Kitapçılık Ltd.Şti. 567- 587.
  • Liao JK., 2002. Beyond lipid lowering: the role of statins in vascular protection. Int. J. Cardiol. 86, 5–18.
  • Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V, ve ark., 1999. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) Study. Circulation. 99, 216–223
  • Prospective studies collaborations., 1995. Cholesterol, diastolic blood pressure, and stroke: 13000 strokes in 450 000 people in 45 prospective cohorts. Lancet. 346, 1647–1653
  • Rosenson RS, Tangey CC.,1998. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 279 20, 1643–1650.
  • Rockwood K, Kirkland S, Hogan DB., 2002. Use of lipid-lowering agents, indication bias, and the risk of dementia in commuity- dwelling elderly people. Arch Neurol. 59, 223–227.
  • Sena A, Pedrosa R, Morais MG., 2003. Therapeutic potential of lovastatin in multiple sclerosis. J. Neurol. 250, 754–755.
  • Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, ve ark., 1995. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 333, 1301–1307.
  • Simons M, Keller P, Dichgans J., 2000. Cholesterol and Alzheimer’s disease: Is there a link. Neurology. 57,1089–1093.
  • SPARCL Investigators. 2006. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355, 549–559.
  • Stanislaus R, Singh AK, Singh I., 2001. Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis. J Neurosci Res. 66,155–162.
  • Sterzer P, Meintzschel F, Rosler A., 2001. Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small vessel disease. Stroke. 32, 2817–2820.
  • Takemoto M, Liao JK., 2001. Pleiotropic effects of 3-hydroxy–3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 21,1712–1719.
  • TenDam VH, Bollen EL, Westendorp RG., Role of statins in prevention of stroke and dementia. Ned Tijdschr Geneeskd. 145,1918– 1921.
  • Warshafsky S, Packard D, Marks SJ, Sachdeva N, Terashita DM, Kaufman G, ve ark., 1999. Efficacy of 3-hydroxy-3- methylglu- taryl coenzyme a reductase inhibitors for prevention of stroke. J Gen Intern Med. 14,763–774.
  • Vaughan CJ, Murphy MB, Buckley BM., 1998. Statins do more than just lower cholesterol. Lancet. 348,1079–1082.
  • Vaughan CJ, Delanty N., 1999. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke. 30, 1969–1973.
  • Vaughan CJ, Delanty N, Basson CT., 2001. Do statins afford neuroprotection in patients with cerebral ischemia and stroke. CNS Drugs. 15, 589-596.
  • Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic-Plese S, ve ark., 2004. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet. 363, 1607–1608
  • Yano K, Reed DM, MacLean CJ., 1989. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke. 20, 4605
There are 37 citations in total.

Details

Primary Language English
Journal Section Internal Medical Sciences
Authors

Yakup Türkel This is me

Murat Terzi This is me

Publication Date December 6, 2010
Submission Date June 17, 2010
Published in Issue Year 2009 Volume: 26 Issue: 2

Cite

APA Türkel, Y., & Terzi, M. (2010). Statinlerin Nöroloji Pratiğindeki Yeri. Journal of Experimental and Clinical Medicine, 26(2), 55-61. https://doi.org/10.5835/jecm.v26i2.1330
AMA Türkel Y, Terzi M. Statinlerin Nöroloji Pratiğindeki Yeri. J. Exp. Clin. Med. December 2010;26(2):55-61. doi:10.5835/jecm.v26i2.1330
Chicago Türkel, Yakup, and Murat Terzi. “Statinlerin Nöroloji Pratiğindeki Yeri”. Journal of Experimental and Clinical Medicine 26, no. 2 (December 2010): 55-61. https://doi.org/10.5835/jecm.v26i2.1330.
EndNote Türkel Y, Terzi M (December 1, 2010) Statinlerin Nöroloji Pratiğindeki Yeri. Journal of Experimental and Clinical Medicine 26 2 55–61.
IEEE Y. Türkel and M. Terzi, “Statinlerin Nöroloji Pratiğindeki Yeri”, J. Exp. Clin. Med., vol. 26, no. 2, pp. 55–61, 2010, doi: 10.5835/jecm.v26i2.1330.
ISNAD Türkel, Yakup - Terzi, Murat. “Statinlerin Nöroloji Pratiğindeki Yeri”. Journal of Experimental and Clinical Medicine 26/2 (December 2010), 55-61. https://doi.org/10.5835/jecm.v26i2.1330.
JAMA Türkel Y, Terzi M. Statinlerin Nöroloji Pratiğindeki Yeri. J. Exp. Clin. Med. 2010;26:55–61.
MLA Türkel, Yakup and Murat Terzi. “Statinlerin Nöroloji Pratiğindeki Yeri”. Journal of Experimental and Clinical Medicine, vol. 26, no. 2, 2010, pp. 55-61, doi:10.5835/jecm.v26i2.1330.
Vancouver Türkel Y, Terzi M. Statinlerin Nöroloji Pratiğindeki Yeri. J. Exp. Clin. Med. 2010;26(2):55-61.