Effects of Lipid-Lowering by Simvastatin on Human Atherosclerotic Lesions: A Longitudinal Study by High-Resolution, Noninvasive Magnetic Resonance Imaging

Background—This study was designed to investigate the effects of lipid-lowering by simvastatin on human atherosclerotic lesions. Methods and Results—Eighteen asymptomatic hypercholesterolemic patients with documented aortic and/or carotid atherosclerotic plaques were selected for the study. A total of 35 aortic and 25 carotid artery plaques were detected. Serial black-blood MRI of the aorta and carotid artery of the patients was performed at baseline and 6 and 12 months after lipid-lowering therapy with simvastatin. The effects of the treatment on atherosclerotic lesions were measured as changes in lumen area, vessel wall thickness, and vessel wall area, a surrogate of atherosclerotic burden. Simvastatin induced a significant (P <0.01) reduction in total and LDL cholesterol levels at 6 weeks that was maintained thereafter. At 6 months, no changes in lumen area, vessel wall thickness, or vessel wall area were observed. However, at 12 months, significant reductions in vessel wall thickness and vessel wall area, without changes in lumen area, were observed in both aortic and carotid arteries (P <0.001). Conclusions—This in vivo human study demonstrates that effective and maintained lipid-lowering therapy by simvastatin is associated with a significant regression of atherosclerotic lesions. Our observation suggests that statins induce vascular remodeling, as manifested by reduced atherosclerotic burden without changes in the lumen.

[1]  P. Shah,et al.  Pravastatin Treatment Increases Collagen Content and Decreases Lipid Content, Inflammation, Metalloproteinases, and Cell Death in Human Carotid Plaques: Implications for Plaque Stabilization , 2001, Circulation.

[2]  A. Gotto,et al.  The evolving role of statins in the management of atherosclerosis. , 2000, Journal of the American College of Cardiology.

[3]  P. Libby,et al.  MRI of rabbit atherosclerosis in response to dietary cholesterol lowering. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[4]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[5]  J. Albers,et al.  Lipid Lowering and Plaque Regression New Insights Into Prevention of Plaque Disruption and Clinical Events in Coronary Disease , 1993, Circulation.

[6]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (1). , 1992, The New England journal of medicine.

[7]  M. Davies,et al.  Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. , 1993, British heart journal.

[8]  P. Libby,et al.  Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. , 1998, Circulation.

[9]  Chun Yuan,et al.  Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo , 1995, Nature Medicine.

[10]  Samin K. Sharma,et al.  Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging. , 2000, Circulation.

[11]  R. Virmani,et al.  Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[12]  V. Fuster,et al.  In vivo magnetic resonance evaluation of atherosclerotic plaques in the human thoracic aorta: a comparison with transesophageal echocardiography. , 2000, Circulation.

[13]  C. Zarins,et al.  Compensatory enlargement of human atherosclerotic coronary arteries. , 1987, The New England journal of medicine.

[14]  C Yuan,et al.  Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging. , 1998, Circulation.

[15]  V. Fuster,et al.  Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. , 1996, Circulation.

[16]  V. Fuster,et al.  Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. , 2000, Circulation.

[17]  C Yuan,et al.  Surface coil phased arrays for high‐resolution imaging of the carotid arteries , 1996, Journal of magnetic resonance imaging : JMRI.

[18]  V. Fuster,et al.  Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. , 1997, Circulation.

[19]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.