| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 1997;28:2315-2320.)
© 1997 American Heart Association, Inc.
Articles |
From the Departments of Neurology (N.D.) and Medicine (C.J.V.), New York Hospital, Cornell Medical Center, New York, NY.
Correspondence to Carl J. Vaughan, MD, Department of Medicine, New York HospitalCornell Medical Center, 525 E 68th St, New York, NY 10021. E-mail cvaughan{at}nyhs.med.cornell.edu
Background Recent clinical trials and meta-analyses of ß-hydroxy-ß-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated a reduction in ischemic stroke in patients with a history of coronary artery disease both with and without elevations of serum cholesterol. This review summarizes clinical trials of these compounds and their recent impact on stroke and explores the underlying vascular mechanisms of their actions.
Summary of Review Use of statins in patients with vascular disease has been shown to lower the incidence of stroke by approximately 30%. Statins exhibit a number of antiatherosclerotic and antithrombotic properties that likely underlie the recently observed reductions in cerebrovascular disease. Statins reduce inflammatory, proliferative, and thrombogenic processes in plaque, making it less likely to rupture. Additionally, they reverse the endothelial dysfunction and platelet activation accompanying hypercholesterolemia and may reduce the tendency to thrombosis.
Conclusions Hypercholesterolemia has reemerged as a risk factor for ischemic stroke. Statins protect against thromboembolic stroke through multiple beneficial effects within the vascular milieu. Further data are awaited to support the growing importance of cholesterol as a risk factor for ischemic stroke and the benefits of statin therapy in patients with cerebrovascular disease.
Key Words: cholesterol HMG-CoA reductase inhibitors hypercholesterolemia
This article has been cited by other articles:
![]() |
C. Schmeer, A. Gamez, S. Tausch, O. W. Witte, and S. Isenmann Statins Modulate Heat Shock Protein Expression and Enhance Retinal Ganglion Cell Survival after Transient Retinal Ischemia/Reperfusion In Vivo Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4971 - 4981. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Rosengarten, D. Auch, and M. Kaps Effects of Initiation and Acute Withdrawal of Statins on the Neurovascular Coupling Mechanism in Healthy, Normocholesterolemic Humans Stroke, December 1, 2007; 38(12): 3193 - 3197. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Amarenco, L. B. Goldstein, M. Szarek, H. Sillesen, A. E. Rudolph, A. Callahan III, M. Hennerici, L. Simunovic, J. A. Zivin, K. M. A. Welch, et al. Effects of Intense Low-Density Lipoprotein Cholesterol Reduction in Patients With Stroke or Transient Ischemic Attack: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial Stroke, December 1, 2007; 38(12): 3198 - 3204. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Blanco, F. Nombela, M. Castellanos, M. Rodriguez-Yanez, M. Garcia-Gil, R. Leira, I. Lizasoain, J. Serena, J. Vivancos, M. A. Moro, et al. Statin treatment withdrawal in ischemic stroke: A controlled randomized study Neurology, August 28, 2007; 69(9): 904 - 910. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. K. Sampson, M. A. Pfeffer, J. J.V. McMurray, Y. Lokhnygina, H. D. White, S. D. Solomon, and for the Valsartan in Acute Myocardial iNfarcTion ( Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT trial Eur. Heart J., March 2, 2007; 28(6): 685 - 691. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Nagaoka, T. W. Hein, A. Yoshida, and L. Kuo Simvastatin Elicits Dilation of Isolated Porcine Retinal Arterioles: Role of Nitric Oxide and Mevalonate-Rho Kinase Pathways Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 825 - 832. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Nagaoka, A. Takahashi, E. Sato, N. Izumi, T. W. Hein, L. Kuo, and A. Yoshida Effect of systemic administration of simvastatin on retinal circulation. Arch Ophthalmol, May 1, 2006; 124(5): 665 - 670. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-Y. Tseng, M. Czosnyka, H. Richards, J. D. Pickard, and P. J. Kirkpatrick Effects of Acute Treatment With Pravastatin on Cerebral Vasospasm, Autoregulation, and Delayed Ischemic Deficits After Aneurysmal Subarachnoid Hemorrhage: A Phase II Randomized Placebo-Controlled Trial Stroke, August 1, 2005; 36(8): 1627 - 1632. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Amarenco and A. M. Tonkin Statins for Stroke Prevention: Disappointment and Hope Circulation, June 15, 2004; 109(23_suppl_1): III-44 - III-49. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Kleemann, H. M.G. Princen, J. J. Emeis, J. W. Jukema, R. D. Fontijn, A. J.G. Horrevoets, T. Kooistra, and L. M. Havekes Rosuvastatin Reduces Atherosclerosis Development Beyond and Independent of Its Plasma Cholesterol-Lowering Effect in APOE*3-Leiden Transgenic Mice: Evidence for Antiinflammatory Effects of Rosuvastatin Circulation, September 16, 2003; 108(11): 1368 - 1374. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M Buckley Review: Lipids and stroke The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 170 - 176. [Abstract] [PDF] |
||||
![]() |
M. Sasaki, S. Bharwani, P. Jordan, T. Joh, K. Manas, A. Warren, H. Harada, P. Carter, J. W. Elrod, M. Wolcott, et al. The 3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitor Pravastatin Reduces Disease Activity and Inflammation in Dextran-Sulfate Induced Colitis J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 78 - 85. [Abstract] [Full Text] |
||||
![]() |
J.-C. Corvol, A. Bouzamondo, M. Sirol, J.-S. Hulot, P. Sanchez, and P. Lechat Differential Effects of Lipid-Lowering Therapies on Stroke Prevention: A Meta-analysis of Randomized Trials Arch Intern Med, March 24, 2003; 163(6): 669 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Sironi, M. Cimino, U. Guerrini, A. M. Calvio, B. Lodetti, M. Asdente, W. Balduini, R. Paoletti, and E. Tremoli Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 322 - 327. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Gertz, U. Laufs, U. Lindauer, G. Nickenig, M. Bohm, U. Dirnagl, and M. Endres Withdrawal of Statin Treatment Abrogates Stroke Protection in Mice Stroke, February 1, 2003; 34(2): 551 - 557. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kawashima, T. Yamashita, Y. Miwa, M. Ozaki, M. Namiki, T. Hirase, N. Inoue, K.-i. Hirata, and M. Yokoyama HMG-CoA Reductase Inhibitor Has Protective Effects Against Stroke Events in Stroke-Prone Spontaneously Hypertensive Rats Stroke, January 1, 2003; 34(1): 157 - 163. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Di Napoli, A.A. Taccardi, M. Oliver, and R. De Caterina Statins and stroke: evidence for cholesterol-independent effects Eur. Heart J., December 2, 2002; 23(24): 1908 - 1921. [PDF] |
||||
![]() |
M. Honjo, H. Tanihara, K. Nishijima, J. Kiryu, Y. Honda, B. Y. J. T. Yue, and T. Sawamura Statin Inhibits Leukocyte-Endothelial Interaction and Prevents Neuronal Death Induced by Ischemia-Reperfusion Injury in the Rat Retina Arch Ophthalmol, December 1, 2002; 120(12): 1707 - 1713. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. B. Gorelick Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review Stroke, March 1, 2002; 33(3): 862 - 875. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Amarenco Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction Neurology, September 1, 2001; 57(90002): S35 - 44. [Abstract] [Full Text] |
||||
![]() |
R. Scalia, M. E. Gooszen, S. P. Jones, M. Hoffmeyer, D. M. Rimmer III, S. D. Trocha, P. L. Huang, M. B. Smith, A. M. Lefer, and D. J. Lefer Simvastatin Exerts Both Anti-inflammatory and Cardioprotective Effects in Apolipoprotein E-Deficient Mice Circulation, May 29, 2001; 103(21): 2598 - 2603. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Alberts Suppression of recurrent transient ischemic attacks by a statin agent Neurology, February 27, 2001; 56(4): 531 - 532. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Circulation, January 2, 2001; 103(1): 163 - 182. [Full Text] [PDF] |
||||
![]() |
L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Stroke, January 1, 2001; 32(1): 280 - 299. [Full Text] [PDF] |
||||
![]() |
U. Laufs, K. Gertz, P. Huang, G. Nickenig, M. Bohm, U. Dirnagl, M. Endres, and C. J. Vaughan Atorvastatin Upregulates Type III Nitric Oxide Synthase in Thrombocytes, Decreases Platelet Activation, and Protects From Cerebral Ischemia in Normocholesterolemic Mice Editorial Comment Stroke, October 1, 2000; 31(10): 2442 - 2449. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J Milionis, A. F Winder, and D. P Mikhailidis Lipoprotein (a) and stroke J. Clin. Pathol., July 1, 2000; 53(7): 487 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Vaughan, A. M. Gotto Jr., and C. T. Basson The evolving role of statins in the management of atherosclerosis J. Am. Coll. Cardiol., January 1, 2000; 35(1): 1 - 10. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J VAUGHAN, N. DELANTY, and D. O'MAHONY Nitric oxide in acute ischaemic stroke J. Neurol. Neurosurg. Psychiatry, January 1, 2000; 68(1): 123 - 123. [Full Text] |
||||
![]() |
N. Kato, T. Tamada, T. Nabika, K. Ueno, T. Gotoda, C. Matsumoto, T. Mashimo, M. Sawamura, K. Ikeda, Y. Nara, et al. Identification of Quantitative Trait Loci for Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 223 - 229. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. DELANTY, A ALGRA, J VAN GIJN, A ALGRA, and P J KOUDSTAAL Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone? J. Neurol. Neurosurg. Psychiatry, December 1, 1999; 67(6): 832a - 833. [Full Text] |
||||
![]() |
D. Pruefer, R. Scalia, and A. M. Lefer Simvastatin Inhibits Leukocyte-Endothelial Cell Interactions and Protects Against Inflammatory Processes in Normocholesterolemic Rats Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2894 - 2900. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. R Mohler III, N. Delanty, D. J Rader, and E. C Raps Statins and cerebrovascular disease: plaque attack to prevent brain attack Vascular Medicine, November 1, 1999; 4(4): 269 - 272. [Abstract] [PDF] |
||||
![]() |
C. J. Vaughan and N. Delanty Neuroprotective Properties of Statins in Cerebral Ischemia and Stroke Stroke, September 1, 1999; 30(9): 1969 - 1973. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Lefer, B. Campbell, Y.-K. Shin, R. Scalia, R. Hayward, and D. J. Lefer Simvastatin Preserves the Ischemic-Reperfused Myocardium in Normocholesterolemic Rat Hearts Circulation, July 13, 1999; 100(2): 178 - 184. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. B. Gorelick, R. L. Sacco, D. B. Smith, M. Alberts, L. Mustone-Alexander, D. Rader, J. L. Ross, E. Raps, M. N. Ozer, L. M. Brass, et al. Prevention of a First Stroke: A Review of Guidelines and a Multidisciplinary Consensus Statement From the National Stroke Association JAMA, March 24, 1999; 281(12): 1112 - 1120. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. F. Plehn, B. R. Davis, F. M. Sacks, J. L. Rouleau, M. A. Pfeffer, V. Bernstein, T. E. Cuddy, L. A. Moye, L. B. Piller, J. Rutherford, et al. Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin : The Cholesterol and Recurrent Events (CARE) Study Circulation, January 19, 1999; 99(2): 216 - 223. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A Papadakis, D. P Mikhailidis, and A. F Winder Lipids and stroke: neglect of a useful preventive measure? Cardiovasc Res, November 1, 1998; 40(2): 265 - 271. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Satoh, K. Ichihara, E. J. Landon, T. Inagami, and H. Tang 3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors Block Calcium-dependent Tyrosine Kinase Pyk2 Activation by Angiotensin II in Vascular Endothelial Cells. INVOLVEMENT OF GERANYLGERANYLATION OF SMALL G PROTEIN Rap1 J. Biol. Chem., May 4, 2001; 276(19): 15761 - 15767. [Abstract] [Full Text] [PDF] |
||||
|
Stroke Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1997 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |