Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.

PURPOSE To investigate whether short-term, intensive lipid therapy leads to changes in microvascular characteristics, as measured by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained for this HIPAA-compatible study. Subjects with established coronary artery disease or carotid artery stenosis of 15% or greater determined by using ultrasonography and with levels of apolipoprotein B of 120 mg/dL (1.2 g/L) or greater were enrolled in an ongoing study (clinical trial NCT00715273). All received intensive lipid therapy to achieve targeted high- and low-density lipoprotein cholesterol levels and underwent serial serum monitoring including high-sensitivity C-reactive protein (HsCRP) level measurements. Carotid artery MR imaging examinations including morphologic and DCE MR images were obtained at baseline and 1 year after treatment. In subjects with advanced lesions (>2 mm thick), MR image analysis was performed, including measurement of lipid-rich necrotic core size and kinetic modeling of DCE MR images to assess changes in the transfer constant (K(trans)). The differences in K(trans) between baseline and 1-year follow-up were compared by using the Wilcoxon signed rank test, and associations were assessed by using the Spearman rank correlation coefficient. RESULTS Twenty-eight subjects with interpretable DCE MR imaging results at both baseline and 1-year follow-up were included. After 1 year of treatment, a significant reduction was found in mean K(trans) (0.085 min(-1) ± 0.037 [standard deviation] to 0.067 min(-1) ± 0.028, P = .02). Reduction in K(trans) was not significantly correlated with observed reductions in lipid-rich necrotic core size or reductions in HsCRP level. CONCLUSION These findings suggest that DCE MR imaging may be a useful imaging method for the assessment of the therapeutic response of the vasa vasorum in patients with atherosclerotic plaque.

[1]  Linda Lavery,et al.  Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. , 2011, European heart journal.

[2]  Folkert J Ten Cate,et al.  Contrast-enhanced ultrasound for imaging vasa vasorum: comparison with histopathology in a swine model of atherosclerosis. , 2010, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[3]  Dan Adam,et al.  Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. , 2010, JACC. Cardiovascular imaging.

[4]  Takahiko Suzuki,et al.  Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound. , 2009, JACC. Cardiovascular interventions.

[5]  E. Boerwinkle,et al.  Correlates of Carotid Plaque Presence and Composition as Measured by MRI: The Atherosclerosis Risk in Communities Study , 2009, Circulation. Cardiovascular imaging.

[6]  Martin J Graves,et al.  The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. , 2009, Journal of the American College of Cardiology.

[7]  Roberto Chiesa,et al.  Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. , 2009, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[8]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[9]  Juan F Granada,et al.  Imaging of the vasa vasorum , 2008, Nature Clinical Practice Cardiovascular Medicine.

[10]  Roberto Chiesa,et al.  Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries: correlation with histology and plaque echogenicity. , 2008, Journal of the American College of Cardiology.

[11]  V. Kamanna,et al.  Mechanism of action of niacin. , 2008, The American journal of cardiology.

[12]  W S Kerwin,et al.  MR imaging of adventitial vasa vasorum in carotid atherosclerosis , 2008, Magnetic resonance in medicine.

[13]  Chun Yuan,et al.  Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. , 2008, American heart journal.

[14]  R. Kronmal,et al.  Risk Factor Associations With the Presence of a Lipid Core in Carotid Plaque of Asymptomatic Individuals Using High-Resolution MRI: The Multi-Ethnic Study of Atherosclerosis (MESA) , 2008, Stroke.

[15]  Nader Rifai,et al.  Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[16]  Fei Liu,et al.  Magnetic Resonance Imaging of Carotid Atherosclerosis: Plaque Analysis , 2007, Topics in magnetic resonance imaging : TMRI.

[17]  Amir Lerman,et al.  The dynamic vasa vasorum. , 2007, Cardiovascular research.

[18]  W Robert Taylor,et al.  The role of the adventitia in vascular inflammation. , 2007, Cardiovascular research.

[19]  C. Yuan,et al.  Testing the hypothesis of atherosclerotic plaque lipid depletion during lipid therapy by magnetic resonance imaging: study design of Carotid Plaque Composition Study. , 2007, American heart journal.

[20]  Dongxiang Xu,et al.  Reader and platform reproducibility for quantitative assessment of carotid atherosclerotic plaque using 1.5T Siemens, Philips, and General Electric scanners , 2007, Journal of magnetic resonance imaging : JMRI.

[21]  A. Hofman,et al.  Atherosclerosis and risk for dementia , 2007, Annals of neurology.

[22]  Raquel Soares,et al.  Angiogenesis and chronic inflammation: cause or consequence? , 2007, Angiogenesis.

[23]  M. Hanefeld,et al.  Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study. , 2007, Journal of the American College of Cardiology.

[24]  Chun Yuan,et al.  Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study. , 2006, Radiology.

[25]  Fei Liu,et al.  MRI of atherosclerosis in clinical trials , 2006, NMR in biomedicine.

[26]  Y. Aizawa,et al.  The anti-atherosclerotic effects of lipid lowering with atorvastatin in patients with hypercholesterolemia. , 2006, Journal of atherosclerosis and thrombosis.

[27]  V. Fuster,et al.  Neovascularization in human atherosclerosis. , 2006, Current molecular medicine.

[28]  R. Cury,et al.  Intra‐ and interreader reproducibility of magnetic resonance imaging for quantifying the lipid‐rich necrotic core is improved with gadolinium contrast enhancement , 2006, Journal of magnetic resonance imaging : JMRI.

[29]  Marc Sirol,et al.  Neovascularization in Human Atherosclerosis , 2006, Circulation.

[30]  Chun Yuan,et al.  In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque: Comparison of High-Resolution, Contrast-Enhanced Magnetic Resonance Imaging and Histology , 2005, Circulation.

[31]  Aloke V. Finn,et al.  Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[32]  M. Bo,et al.  Cognitive function after carotid endarterectomy: greater risk of decline in symptomatic patients with left internal carotid artery disease. , 2005, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[33]  C. Yuan,et al.  Quantitative Evaluation of Carotid Plaque Composition by In Vivo MRI , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[34]  R B D'Agostino,et al.  Stroke risk profile, brain volume, and cognitive function , 2004, Neurology.

[35]  P. Wolf,et al.  Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study. , 2004, Journal of lipid research.

[36]  H. Markus,et al.  Rates and Determinants of Site-Specific Progression of Carotid Artery Intima-Media Thickness: The Carotid Atherosclerosis Progression Study , 2004, Stroke.

[37]  Charles DeCarli,et al.  Stroke Risk Profile Predicts White Matter Hyperintensity Volume: The Framingham Study , 2004, Stroke.

[38]  Chun Yuan,et al.  Hemorrhage in the Atherosclerotic Carotid Plaque: A High-Resolution MRI Study , 2004, Stroke.

[39]  O. Joakimsen,et al.  Reduced neuropsychological test performance in asymptomatic carotid stenosis , 2004, Neurology.

[40]  L. Fried,et al.  Cognitive Impairment and Decline Are Associated with Carotid Artery Disease in Patients without Clinically Evident Cerebrovascular Disease , 2004, Annals of Internal Medicine.

[41]  Renu Virmani,et al.  Intraplaque hemorrhage and progression of coronary atheroma. , 2003, The New England journal of medicine.

[42]  David Zurakowski,et al.  Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Hofman,et al.  Silent brain infarcts and the risk of dementia and cognitive decline. , 2003, The New England journal of medicine.

[44]  Chun Yuan,et al.  Quantitative Magnetic Resonance Imaging Analysis of Neovasculature Volume in Carotid Atherosclerotic Plaque , 2003, Circulation.

[45]  V. Fuster,et al.  Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions: Two Years’ Follow-Up by High-Resolution Noninvasive Magnetic Resonance Imaging , 2002, Circulation.

[46]  W S Kerwin,et al.  Noise and motion correction in dynamic contrast‐enhanced MRI for analysis of atherosclerotic lesions , 2002, Magnetic resonance in medicine.

[47]  P. Libby,et al.  Inflammation and Atherosclerosis , 2002, Circulation.

[48]  E. Ritman,et al.  Simvastatin Preserves the Structure of Coronary Adventitial Vasa Vasorum in Experimental Hypercholesterolemia Independent of Lipid Lowering , 2002, Circulation.

[49]  E. Ritman,et al.  Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia. , 2001, Cardiovascular research.

[50]  M. Bond,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 , 2001, Stroke.

[51]  A. Folsom,et al.  Cardiovascular risk factors and cognitive decline in middle-aged adults , 2001, Neurology.

[52]  Roberta F. White,et al.  The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort. , 2000, Archives of neurology.

[53]  Debashis Kushary,et al.  Bootstrap Methods and Their Application , 2000, Technometrics.

[54]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[55]  D. Woolley,et al.  Local neovascularization and cellular composition within vulnerable regions of atherosclerotic plaques of human carotid arteries , 1999, The Journal of pathology.

[56]  T. Manolio,et al.  Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[57]  R. Kronmal,et al.  Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. , 1999, The New England journal of medicine.

[58]  E L Ritman,et al.  Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. , 1998, The Journal of clinical investigation.

[59]  P. Libby,et al.  Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. , 1998, Journal of the American College of Cardiology.

[60]  R. D'Agostino,et al.  Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. , 1997, The New England journal of medicine.

[61]  J. O'Brien,et al.  White matter lesions in depression and Alzheimer's disease , 1996, British Journal of Psychiatry.

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

[63]  J. J. Claus,et al.  Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study , 1994, BMJ.

[64]  R A Kronmal,et al.  Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack. , 1993, Radiology.

[65]  L. Chambless,et al.  Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. , 1991, American journal of epidemiology.

[66]  R B D'Agostino,et al.  Probability of stroke: a risk profile from the Framingham Study. , 1991, Stroke.

[67]  A. Barger,et al.  Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. , 1984, The New England journal of medicine.

[68]  C S Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data , 1983, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[69]  W. Kannel,et al.  An investigation of coronary heart disease in families. The Framingham offspring study. , 1979, American journal of epidemiology.