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Circulation. 1994;90:1679-1687

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*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Carotid Artery Disease
Hazardous Substances DB
*LOVASTATIN
*WARFARIN

Circulation, Vol 90, 1679-1687, Copyright © 1994 by American Heart Association


ARTICLES

Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group

CD Furberg, HP Adams Jr, WB Applegate, RP Byington, MA Espeland, T Hartwell, DB Hunninghake, DS Lefkowitz, J Probstfield and WA Riley
Department of Public Health Sciences, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1063.

BACKGROUND: HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease. METHODS AND RESULTS: Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02). CONCLUSIONS: In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.


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L. E. Chambless, A. R. Folsom, V. Davis, R. Sharrett, G. Heiss, P. Sorlie, M. Szklo, G. Howard, and G. W. Evans
Risk Factors for Progression of Common Carotid Atherosclerosis: The Atherosclerosis Risk in Communities Study, 1987-1998
Am. J. Epidemiol., January 1, 2002; 155(1): 38 - 47.
[Abstract] [Full Text] [PDF]


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NEJMHome page
R. L. Sacco
Extracranial Carotid Stenosis
N. Engl. J. Med., October 11, 2001; 345(15): 1113 - 1118.
[Full Text] [PDF]


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StrokeHome page
P. Rubba, S. Panico, M. G. Bond, G. Covetti, E. Celentano, A. Iannuzzi, R. Galasso, M. A. Belisario, A. Pastinese, L. Sacchetti, et al.
Site-Specific Atherosclerotic Plaques in the Carotid Arteries of Middle-Aged Women From Southern Italy: Associations With Traditional Risk Factors and Oxidation Markers
Stroke, September 1, 2001; 32(9): 1953 - 1959.
[Abstract] [Full Text] [PDF]


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NeurologyHome page
P. Amarenco
Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction
Neurology, September 1, 2001; 57(90002): S35 - 44.
[Abstract] [Full Text]


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CirculationHome page
B. Hedblad, J. Wikstrand, L. Janzon, H. Wedel, and G. Berglund
Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness : Main Results From the {beta}-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS)
Circulation, April 3, 2001; 103(13): 1721 - 1726.
[Abstract] [Full Text] [PDF]


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QJMHome page
S. Bandyopadhyay, A.J. Bayer, and M.S. O'Mahony
Age and gender bias in statin trials
QJM, March 1, 2001; 94(3): 127 - 132.
[Abstract] [Full Text] [PDF]


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Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
W. S. Aronow
Treatment of Older Persons With Hypercholesterolemia With and Without Cardiovascular Disease
J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2001; 56(3): 138M - 145.
[Abstract] [Full Text]


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ANGIOLOGYHome page
T. J. Tegos, E. Kalodiki, M. M. Sabetai, and A. N. Nicolaides
The Genesis of Atherosclerosis and Risk Factors: A Review
Angiology, February 1, 2001; 52(2): 89 - 98.
[Abstract] [PDF]


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CirculationHome page
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]


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Eur Heart JHome page
C. Held, P. Hjemdahl, S.V. Eriksson, I. Bjorkander, L. Forslund, and N. Rehnqvist
Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris
Eur. Heart J., January 1, 2001; 22(1): 62 - 72.
[Abstract] [PDF]


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StrokeHome page
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]


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J Am Coll CardiolHome page
M. Rubenfire, S. Rajagopalan, and L. Mosca
Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness
J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2192 - 2197.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. Hsia, J. A. Simon, F. Lin, W. B. Applegate, M. T. Vogt, D. Hunninghake, and M. Carr
Peripheral Arterial Disease in Randomized Trial of Estrogen With Progestin in Women With Coronary Heart Disease : The Heart and Estrogen/Progestin Replacement Study
Circulation, October 31, 2000; 102(18): 2228 - 2232.
[Abstract] [Full Text] [PDF]


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BMJHome page
M. Pignone, C. Phillips, and C. Mulrow
Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials
BMJ, October 21, 2000; 321(7267): 983 - 986.
[Abstract] [Full Text]


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CirculationHome page
B. Pitt, R. P. Byington, C. D. Furberg, D. B. Hunninghake, G. B. J. Mancini, M. E. Miller, and W. Riley
Effect of Amlodipine on the Progression of Atherosclerosis and the Occurrence of Clinical Events
Circulation, September 26, 2000; 102(13): 1503 - 1510.
[Abstract] [Full Text] [PDF]


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NEJMHome page
H. D. White, R. J. Simes, N. E. Anderson, G. J. Hankey, J. D.G. Watson, D. Hunt, D. M. Colquhoun, P. Glasziou, S. MacMahon, A. C. Kirby, et al.
Pravastatin Therapy and the Risk of Stroke
N. Engl. J. Med., August 3, 2000; 343(5): 317 - 326.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
P. Sun, K. M. Dwyer, C. N. B. Merz, W. Sun, C. A. Johnson, A. M. Shircore, and J. H. Dwyer
Blood Pressure, LDL Cholesterol, and Intima-Media Thickness : A Test of the "Response to Injury" Hypothesis of Atherosclerosis
Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 2005 - 2010.
[Abstract] [Full Text] [PDF]


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StrokeHome page
D. Baldassarre, E. Tremoli, M. Amato, F. Veglia, A. Bondioli, and C. R. Sirtori
Reproducibility Validation Study Comparing Analog and Digital Imaging Technologies for the Measurement of Intima-Media Thickness
Stroke, May 1, 2000; 31(5): 1104 - 1110.
[Abstract] [Full Text] [PDF]


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Am. J. Neuroradiol.Home page
J. J. Connors III, D. Seidenwurm, J. C. Wojak, R. W. Hurst, M. E. Jensen, R. Wallace, T. Tomsick, J. Barr, C. Kerber, E. Russell, et al.
Treatment of Atherosclerotic Disease at the Cervical Carotid Bifurcation: Current Status and Review of the Literature
AJNR Am. J. Neuroradiol., March 1, 2000; 21(3): 444 - 450.
[Full Text]


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LupusHome page
S Manzi, L H Kuller, D Edmundowicz, and K Sutton-Tyrrell
Vascular imaging: changing the face of cardiovascular research
Lupus, March 1, 2000; 9(3): 176 - 182.
[Abstract] [PDF]


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StrokeHome page
A. Castillo-Richmond, R. H. Schneider, C. N. Alexander, R. Cook, H. Myers, S. Nidich, C. Haney, M. Rainforth, and J. Salerno
Effects of Stress Reduction on Carotid Atherosclerosis in Hypertensive African Americans
Stroke, March 1, 2000; 31(3): 568 - 573.
[Abstract] [Full Text] [PDF]


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NeurologyHome page
D. C. Hess, A. M. Demchuk, L. M. Brass, and F. M. Yatsu
HMG-CoA reductase inhibitors (statins): A promising approach to stroke prevention
Neurology, February 22, 2000; 54(4): 790 - 796.
[Abstract] [Full Text] [PDF]


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CirculationHome page
P. Greenland, J. Abrams, G. P. Aurigemma, M. G. Bond, L. T. Clark, M. H. Criqui, J. R. Crouse III, L. Friedman, V. Fuster, D. M. Herrington, et al.
Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III
Circulation, January 4, 2000; 101 (1): e16 - e22.
[Full Text] [PDF]


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J Am Coll CardiolHome page
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]


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JAMAHome page
J. C. LaRosa, J. He, and S. Vupputuri
Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials
JAMA, December 22, 1999; 282(24): 2340 - 2346.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4516 - 4524.
[Abstract] [Full Text]


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Vasc MedHome page
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]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. Hashimoto, M. Eto, M. Akishita, K. Kozaki, J. Ako, K. Iijima, S. Kim, K. Toba, M. Yoshizumi, and Y. Ouchi
Correlation Between Flow-Mediated Vasodilatation of the Brachial Artery and Intima-Media Thickness in the Carotid Artery in Men
Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2795 - 2800.
[Abstract] [Full Text] [PDF]


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StrokeHome page
G. W. Albers, R. G. Hart, H. L. Lutsep, D. W. Newell, and R. L. Sacco
Supplement to the Guidelines for the Management of Transient Ischemic Attacks : A Statement From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association
Stroke, November 1, 1999; 30(11): 2502 - 2511.
[Full Text] [PDF]


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CirculationHome page
P. H. Davis, J. D. Dawson, L. T. Mahoney, and R. M. Lauer
Increased Carotid Intimal-Medial Thickness and Coronary Calcification Are Related in Young and Middle-Aged Adults : The Muscatine Study
Circulation, August 24, 1999; 100(8): 838 - 842.
[Abstract] [Full Text] [PDF]


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Arch Intern MedHome page
S. D. Ross, I. E. Allen, J. E. Connelly, B. M. Korenblat, M. E. Smith, D. Bishop, and D. Luo
Clinical Outcomes in Statin Treatment Trials: A Meta-analysis
Arch Intern Med, August 9, 1999; 159(15): 1793 - 1802.
[Abstract] [Full Text] [PDF]


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Vasc MedHome page
Y. Nagai, E J. Metter, and J. L Fleg
Increased carotid artery intimal-medial thickness: risk factor for exercise-induced myocardial ischemia in asymptomatic older individuals
Vascular Medicine, August 1, 1999; 4(3): 181 - 186.
[Abstract] [PDF]


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CirculationHome page
R. P. Byington, G. W. Evans, M. A. Espeland, W. B. Applegate, D. B. Hunninghake, J. Probstfield, and C. D. Furberg
Effects of Lovastatin and Warfarin on Early Carotid Atherosclerosis : Sex-Specific Analyses
Circulation, July 20, 1999; 100 (3): e14 - e17.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
S. Kiechl and J. Willeit
The Natural Course of Atherosclerosis : Part I: Incidence and Progression
Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1484 - 1490.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
F. Borson-Chazot, A. Serusclat, Y. Kalfallah, X. Ducottet, G. Sassolas, S. Bernard, F. Labrousse, J. Pastene, A. Sassolas, Y. Roux, et al.
Decrease in Carotid Intima-Media Thickness after One Year Growth Hormone (GH) Treatment in Adults with GH Deficiency
J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1329 - 1333.
[Abstract] [Full Text]


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CirculationHome page
C. D. Furberg
Natural Statins and Stroke Risk
Circulation, January 19, 1999; 99(2): 185 - 188.
[Full Text] [PDF]