Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions
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Objectives This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI).Background Regression of atherosclerotic lesions by lipid-lowering therapy has been reported.Methods Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden.Results Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p < 0.001). Total cholesterol decreased by 26% versus 33% and LDL-C by 36% versus 46% in the conventional (20 mg) versus aggressive (80 mg) simvastatin groups, respectively. Although the simvastatin 80-mg group had significantly higher baseline TC and LDL-C levels, both groups reached similar absolute values after treatment. A significant reduction in VWA was already observed by 12 months. No difference on vascular effects was detected between the randomized doses. Post-hoc analysis showed that patients reaching mean on-treatment LDL-C < or = 100 mg/dl had larger decreases in plaque size.Conclusions Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.
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Morphological high-resolution MRI detects substantial changes in lesion characteristics only after a minimum of a year of high-dose statin treatment.
“In comparison, morphological high-resolution MRI is only able to detect substantial changes in lesion characteristics after a minimum of a year of high-dose statin treatment131”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [131]
USPIO-enhanced MRI may be useful as an imaging biomarker to detect inflammatory changes before morphological changes occur.
“demonstrating that USPIO-enhanced MRI may be useful as an imaging biomarker to detect inflammatory changes before morphological changes occur.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [131]
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Self-citation
- Authors
- Corti, R., Worthley, S. G., Helft, G., Viles-Gonzalez, J. F., Badimon, J. J., Corti, R., Fuster, V., Fayad, Z. A., Worthley, S. G., Helft, G., Chaplin, W. F., Viles-Gonzalez, J. F., Smith, D. A., Mizsei, G., Badimon, J. J., Weinberger, J., Corti, R., & Muntwyler, J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 46
- Issue
- 1
- Pages
- 106-112
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W183477746
- Cited by
- 257
- References
- 29
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 15 · 2014: 13 · 2013: 16 · 2012: 12
- FWCI
- 27.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Heart Foundation of Australia
- National Research Foundation
- Fédération Française de Cardiologie
- National Institutes of Health (5r01hl061801-04)
- National Heart, Lung, and Blood Institute (HL54469, HL 61801, P50HL054469)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- simvastatin, aggressive lipid-lowering therapy, atherosclerotic plaque regression, aortic plaque, carotid plaque, vessel wall area, LDL cholesterol, hypercholesterolemia, statin dose, magnetic resonance imaging, plaque size
- MeSH terms
- Adult, Aged, Aged, 80 and over, Hypolipidemic Agents, Aorta, Thoracic, Arteriosclerosis, Carotid Arteries, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Time Factors, Simvastatin
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