From the Clinical Trials Research Unit and Department of Medicine,
University of Auckland (New Zealand) (S.M., N.S., G.G., J.Scott); the
Department of Medicine, North Shore Hospital, Auckland (H.H.); NH and MRC
Clinical Trials Centre, University of Sydney (Australia) (J.Simes); and
Coronary Care and Cardiovascular Research Units, Greenlane Hospital, Auckland
(H.W.).
Correspondence to Dr Stephen MacMahon, Clinical Trials Research Unit, Department of Medicine, The University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail macmahon{at}ctru.auckland.ac.nz
Background—Cholesterol
lowering in patients with above-average cholesterol levels
has been shown to reduce the progression of
atherosclerosis and lower the risk of coronary
heart disease events. However, there has been uncertainty about the
effects of cholesterol lowering in patients with average or
below-average cholesterol levels.
Methods and Results—In this study, 522 patients with a history of
myocardial infarction or unstable angina and with baseline levels of
total cholesterol between 4 and 7 mmol/L (mean,
5.7 mmol/L) were randomized to treatment with a low fat diet plus
pravastatin (40 mg daily) or to a low fat diet plus
placebo. Treatment with pravastatin reduced the levels of
total cholesterol by 19%, LDL cholesterol by
27%, apolipoprotein B by 19%, and triglycerides by 13%
(all 2P<.0001) and increased apolipoprotein A1 and HDL
cholesterol levels by 4% (both 2P<.0005),
in comparison with placebo. Carotid atherosclerosis was
assessed from B-mode ultrasound measurements of the common carotid
artery. After 4 years, mean carotid wall thickness had increased by
0.048 mm (SE=0.01) in the placebo group and declined by 0.014
mm in the pravastatin-treated group (SE=0.01)
(2P for difference <.0001). The effect of treatment on
wall thickness was similar in three groups classified by tertiles of
total cholesterol at baseline, with mean levels of 4.8,
5.7, and 6.6 mmol/L, respectively (2P for
interaction >.8).
Conclusions—Treatment with pravastatin reduced the
development of carotid atherosclerosis among patients
with coronary heart disease and a wide range of pretreatment
cholesterol levels. Treatment with this agent prevented any
detectable increase in carotid wall thickening over 4 years of
follow-up.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Effects of Lowering Average or Below-Average Cholesterol Levels on the Progression of Carotid Atherosclerosis
Results of the LIPID Atherosclerosis Substudy
Key Words: cholesterol • atherosclerosis • carotid arteries • coronary disease
This article has been cited by other articles:
 |
|
 |
|
  B. V. Howard, M. J. Roman, R. B. Devereux, J. L. Fleg, J. M. Galloway, J. A. Henderson, Wm. J. Howard, E. T. Lee, M. Mete, B. Poolaw, et al. Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes: The SANDS Randomized Trial JAMA, April 9, 2008; 299(14): 1678 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J.P. Kastelein, F. Akdim, E. S.G. Stroes, A. H. Zwinderman, M. L. Bots, A. F.H. Stalenhoef, F. L.J. Visseren, E. J.G. Sijbrands, M. D. Trip, E. A. Stein, et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia N. Engl. J. Med., April 3, 2008; 358(14): 1431 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Reiter, S. Wirth, A. Pourazim, S. Puchner, M. Baghestanian, E. Minar, and R. A. Bucek Skin tissue cholesterol is not related to vascular occlusive disease Vascular Medicine, May 1, 2007; 12(2): 129 - 134. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Yanai, H. Yoshida, Y. Tomono, and N. Tada Atherosclerosis imaging in statin intervention trials QJM, May 1, 2007; 100(5): 253 - 262. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhu, G. Su, and Q. H. Meng Inhibitory Effects of Micronized Fenofibrate on Carotid Atherosclerosis in Patients with Essential Hypertension Clin. Chem., November 1, 2006; 52(11): 2036 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Morimoto, W. J. Janssen, M. B. Fessler, K. A. McPhillips, V. M. Borges, R. P. Bowler, Y.-Q. Xiao, J. A. Kench, P. M. Henson, and R. W. Vandivier Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease. J. Immunol., June 15, 2006; 176(12): 7657 - 7665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-J. Touboul, J. Labreuche, E. Vicaut, P. Amarenco, and on behalf of the GENIC Investigators Carotid Intima-Media Thickness, Plaques, and Framingham Risk Score as Independent Determinants of Stroke Risk Stroke, August 1, 2005; 36(8): 1741 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Campeau, J. Lesperance, L. Bilodeau, A. Fortier, M.-C. Guertin, and G. L. Knatterud Effect of Cholesterol Lowering and Cardiovascular Risk Factors on the Progression of Aortoiliac Arteriosclerosis: A Quantitative Cineangiography Study Angiology, March 1, 2005; 56(2): 191 - 199. [Abstract] [PDF]
|
|
|
|
|
|
F. W. Asselbergs, A. M. van Roon, H. L. Hillege, P. E. de Jong, R. O.B. Gans, A. J. Smit, W. H. van Gilst, and on behalf of the PREVEND IT Investigators Effects of Fosinopril and Pravastatin on Carotid Intima-Media Thickness in Subjects With Increased Albuminuria Stroke, March 1, 2005; 36(3): 649 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Beishuizen, M. A. van de Ree, J. W. Jukema, J. T. Tamsma, J. C. M. van der Vijver, A. E. Meinders, H. Putter, and M. V. Huisman Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease Diabetes Care, December 1, 2004; 27(12): 2887 - 2892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Amarenco, J. Labreuche, P. Lavallee, and P.-J. Touboul Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis Stroke, December 1, 2004; 35(12): 2902 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanchetti, G. Crepaldi, M. G. Bond, G. Gallus, F. Veglia, G. Mancia, A. Ventura, G. Baggio, L. Sampieri, P. Rubba, et al. Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS--A Randomized Double-Blind Trial Stroke, December 1, 2004; 35(12): 2807 - 2812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. J. Mancini, B. Dahlof, and J. Diez Surrogate Markers for Cardiovascular Disease: Structural Markers Circulation, June 29, 2004; 109(25_suppl_1): IV-22 - IV-30. [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]
|
|
|
|
|
|
A. G. Thrift Cholesterol Is Associated With Stroke, but Is Not a Risk Factor Stroke, June 1, 2004; 35(6): 1524 - 1525. [Full Text] [PDF]
|
|
|
|
|
|
J. P.J. Halcox and J. E. Deanfield Beyond the Laboratory: Clinical Implications for Statin Pleiotropy Circulation, June 1, 2004; 109(21_suppl_1): II-42 - II-48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Bots, G. W. Evans, W. A. Riley, and D. E. Grobbee Carotid Intima-Media Thickness Measurements in Intervention Studies: Design Options, Progression Rates, and Sample Size Considerations: A Point of View Stroke, December 1, 2003; 34(12): 2985 - 2994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Tuzcu and P. Schoenhagen Acute coronary syndromes, plaque vulnerability,and carotid artery disease: The changing role ofatherosclerosis imaging J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1033 - 1036. [Full Text] [PDF]
|
|
|
|
|
|
M. K. Duggirala, D. A. Cook, K. F. Mauck, Y. F. Tai, P. Prandoni, A. W.A. Lensing, and M. H. Prins An Association between Atherosclerosis and Venous Thrombosis N. Engl. J. Med., July 24, 2003; 349(4): 401 - 402. [Full Text] [PDF]
|
|
|
|
|
|
A. T Hirsch and A. M Gotto Jr Undertreatment of dyslipidemia in peripheral arterial disease and other high-risk populations: an opportunity for cardiovascular disease reduction Vascular Medicine, November 1, 2002; 7(4): 323 - 331. [Abstract] [PDF]
|
|
|
|
 |
|
 R. P. Byington, C. D. Furberg, D. M. Herrington, J. A. Herd, D. Hunninghake, M. Lowery, W. Riley, T. Craven, L. Chaput, C. C. Ireland, et al. Effect of Estrogen Plus Progestin on Progression of Carotid Atherosclerosis in Postmenopausal Women With Heart Disease: HERS B-Mode Substudy Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1692 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-S. Cheng, D. P. Mikhailidis, G. Hamilton, and A. M. Seifalian A review of the carotid and femoral intima-media thickness as an indicator of the presence of peripheral vascular disease and cardiovascular risk factors Cardiovasc Res, June 1, 2002; 54(3): 528 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Koren-Morag, D. Tanne, E. Graff, U. Goldbourt, and for the Bezafibrate Infarction Prevention Study Gr Low- and High-Density Lipoprotein Cholesterol and Ischemic Cerebrovascular Disease: The Bezafibrate Infarction Prevention Registry Arch Intern Med, May 13, 2002; 162(9): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kreisberg and A. Oberman Lipids and Atherosclerosis: Lessons Learned from Randomized Controlled Trials of Lipid Lowering and Other Relevant Studies J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 423 - 437. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 P. Amarenco Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction Neurology, September 1, 2001; 57(90002): S35 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
L. Diomede, D. Albani, M. Sottocorno, M. B. Donati, M. Bianchi, P. Fruscella, and M. Salmona In Vivo Anti-Inflammatory Effect of Statins Is Mediated by Nonsterol Mevalonate Products Arterioscler. Thromb. Vasc. Biol., August 1, 2001; 21(8): 1327 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hashimoto, K. Kitagawa, H. Hougaku, Y. Shimizu, M. Sakaguchi, Y. Nagai, S. Iyama, H. Yamanishi, M. Matsumoto, and M. Hori C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis Circulation, July 3, 2001; 104(1): 63 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M Nass, J. K Allen, R. M Jermyn, and L. A Fleisher Secondary prevention of coronary artery disease in patients undergoing elective surgery for peripheral arterial disease Vascular Medicine, February 1, 2001; 6(1): 35 - 41. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. P. Byington, B. R. Davis, J. F. Plehn, H. D. White, J. Baker, S. M. Cobbe, and J. Shepherd Reduction of Stroke Events With Pravastatin : The Prospective Pravastatin Pooling (PPP) Project Circulation, January 23, 2001; 103(3): 387 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Zureik, P. Ducimetiere, P.-J. Touboul, D. Courbon, C. Bonithon-Kopp, C. Berr, and C. Magne Common Carotid Intima-Media Thickness Predicts Occurrence of Carotid Atherosclerotic Plaques : Longitudinal Results From the Aging Vascular Study (EVA) Study Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1622 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Golledge, R. M. Greenhalgh, and A. H. Davies The Symptomatic Carotid Plaque Stroke, March 1, 2000; 31(3): 774 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F Oliver Cholesterol and strokes BMJ, February 19, 2000; 320(7233): 459 - 460. [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
B. J. Ansell, K. E. Watson, and A. M. Fogelman An Evidence-Based Assessment of the NCEP Adult Treatment Panel II Guidelines JAMA, December 1, 1999; 282(21): 2051 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Demchuk, D. C. Hess, L. M. Brass, and F. M. Yatsu Is Cholesterol a Risk Factor for Stroke?: Yes Arch Neurol, December 1, 1999; 56(12): 1518 - 1520. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Faggiotto and R. Paoletti Statins and Blockers of the Renin-Angiotensin System : Vascular Protection Beyond Their Primary Mode of Action Hypertension, October 1, 1999; 34(4): 987 - 996. [Abstract] [Full Text] [PDF]
|
|