Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2014

Open Access 01-12-2014 | Research article

Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin

Authors: Ruixue Du, Jianming Cai, Xue-Qiao Zhao, Qing-Jun Wang, Dan-Qing Liu, Wen-Xiu Leng, Peng Gao, Hong-Mei Wu, Lin Ma, Ping Ye

Published in: BMC Cardiovascular Disorders | Issue 1/2014

Login to get access

Abstract

Background

Statin therapy has shown to deplete atherosclerotic plaque lipid content and induce plaque regression. However, how early the plaque lipid depletion can occur with low-density lipoprotein cholesterol (LDL-C) lowering in humans in vivo has not been fully described.

Methods

We enrolled 43 lipid treatment naïve subjects with asymptomatic carotid atherosclerosis and LDL-C ≥ 100 and ≤ 250 mg/dl. Rosuvastatin 5–20 mg/day was used to lower LDL-C levels to < 80 mg/dl. Lipid profile and carotid MRI scans were obtained at baseline, 3, 12, and 24 months. Carotid plaque lipid-rich necrotic core (LRNC) and plaque burden were measured and compared between baseline and during treatment.

Results

Among the 32 subjects who completed the study, at 3 months, an average dose of rosuvastatin of 11 mg/day lowered LDL-C levels by 47% (125.2 ± 24.4 mg/dl vs. 66.7 ± 17.3 mg/dl, p < 0.001). There were no statistically significant changes in total wall volume, percent wall volume or lumen volume. However, LRNC volume was significantly decreased by 7.9 mm3, a reduction of 7.3% (111.5 ± 104.2 mm3 vs. 103.6 ± 95.8 mm3, p = 0.044). Similarly, % LRNC was also significantly decreased from 18.9 ± 11.9% to 17.9 ± 11.5% (p = 0.02) at 3 months. Both LRNC volume and % LRNC continued to decrease moderately at 12 and 24 months, although this trend was not significant.

Conclusions

Among a small number of lipid treatment naïve subjects, rosuvastatin therapy may induce a rapid and lasting decrease in carotid plaque lipid content as assessed by MRI.

Trial registration

ClinicalTrials.Gov numbers NCT00885872
Appendix
Available only for authorised users
Literature
1.
go back to reference Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM: Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000, 20: 1262-1275.CrossRefPubMed Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM: Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000, 20: 1262-1275.CrossRefPubMed
2.
go back to reference Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J: Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993, 69: 377-381.CrossRefPubMedPubMedCentral Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J: Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993, 69: 377-381.CrossRefPubMedPubMedCentral
3.
go back to reference Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C: Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation. 2002, 106: 1368-1373.CrossRefPubMed Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C: Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation. 2002, 106: 1368-1373.CrossRefPubMed
4.
go back to reference Takaya N, Cai J, Ferguson MS, Yarnykh VL, Chu B, Saam T, Polissar NL, Sherwood J, Cury RC, Anders RJ, Broschat KO, Hinton D, Furie KL, Hatsukami TS, Yuan C: Intra- and interreader reproducibility of magnetic resonance imaging for quantifying the lipid-rich necrotic core is improved with gadolinium contrast enhancement. J Magn Reson Imaging. 2006, 24: 203-210.CrossRefPubMed Takaya N, Cai J, Ferguson MS, Yarnykh VL, Chu B, Saam T, Polissar NL, Sherwood J, Cury RC, Anders RJ, Broschat KO, Hinton D, Furie KL, Hatsukami TS, Yuan C: Intra- and interreader reproducibility of magnetic resonance imaging for quantifying the lipid-rich necrotic core is improved with gadolinium contrast enhancement. J Magn Reson Imaging. 2006, 24: 203-210.CrossRefPubMed
5.
go back to reference Cai J, Hatsukami TS, Ferguson MS, Kerwin WS, Saam T, Chu B, Takaya N, Polissar NL, Yuan C: In vivo quantitative measurement of intact fibrous cap and lipid rich necrotic core size in atherosclerotic carotid plaque: a comparison of high resolution contrast enhanced MRI and histology. Circulation. 2005, 112: 3437-3444.CrossRefPubMed Cai J, Hatsukami TS, Ferguson MS, Kerwin WS, Saam T, Chu B, Takaya N, Polissar NL, Yuan C: In vivo quantitative measurement of intact fibrous cap and lipid rich necrotic core size in atherosclerotic carotid plaque: a comparison of high resolution contrast enhanced MRI and histology. Circulation. 2005, 112: 3437-3444.CrossRefPubMed
6.
go back to reference Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ: Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years’ follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002, 106: 2884-2887.CrossRefPubMed Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ: Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years’ follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002, 106: 2884-2887.CrossRefPubMed
7.
go back to reference Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Chaplin WF, Muntwyler J, Viles-Gonzalez JF, Weinberger J, Smith DA, Mizsei G, Badimon JJ: Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2005, 46: 106-112.CrossRefPubMed Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Chaplin WF, Muntwyler J, Viles-Gonzalez JF, Weinberger J, Smith DA, Mizsei G, Badimon JJ: Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2005, 46: 106-112.CrossRefPubMed
8.
go back to reference Underhill HR, Yuan C, Zhao XQ, Kraiss LW, Parker DL, Saam T, Chu B, Takaya N, Liu F, Polissar NL, Neradilek B, Raichlen JS, Cain VA, Waterton JC, Hamar W, Hatsukami TS: Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. Am Heart J. 2008, 155 (584): e1-e8.PubMed Underhill HR, Yuan C, Zhao XQ, Kraiss LW, Parker DL, Saam T, Chu B, Takaya N, Liu F, Polissar NL, Neradilek B, Raichlen JS, Cain VA, Waterton JC, Hamar W, Hatsukami TS: Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. Am Heart J. 2008, 155 (584): e1-e8.PubMed
9.
go back to reference Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C: MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011, 4: 977-986.CrossRefPubMedPubMedCentral Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C: MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011, 4: 977-986.CrossRefPubMedPubMedCentral
10.
go back to reference Joint committee for developing Chinese guidelines on prevention and treatment of dyslipidemia in adults: Chinese guidelines on prevention and treatment of dyslipidemia in adults. Zhong hua Xin Xue Guan Bing Za Zhi. 2007, 35: 390-419. Joint committee for developing Chinese guidelines on prevention and treatment of dyslipidemia in adults: Chinese guidelines on prevention and treatment of dyslipidemia in adults. Zhong hua Xin Xue Guan Bing Za Zhi. 2007, 35: 390-419.
11.
go back to reference Kerwin W, Xu D, Liu F, Saam T, Underhill H, Takaya N, Chu B, Hatsukami T, Yuan C: Magnetic resonance imaging of carotid atherosclerosis: plaque analysis. Top Magn Reson Imaging. 2007, 5: 371-378.CrossRef Kerwin W, Xu D, Liu F, Saam T, Underhill H, Takaya N, Chu B, Hatsukami T, Yuan C: Magnetic resonance imaging of carotid atherosclerosis: plaque analysis. Top Magn Reson Imaging. 2007, 5: 371-378.CrossRef
12.
go back to reference Saam T, Hatsukami TS, Yarnykh VL, Hayes CE, Underhill H, Chu B, Takaya N, Cai J, Kerwin WS, Xu D, Polissar NL, Neradilek B, Hamar WK, Maki J, Shaw DW, Buck RJ, Wyman B, Yuan C: Reader and platform reproducibility for quantitative assessment of carotid atherosclerotic plaque using 1.5T Siemens, philips, and general electric scanners. J Magn Reson Imaging. 2007, 26: 344-352.CrossRefPubMed Saam T, Hatsukami TS, Yarnykh VL, Hayes CE, Underhill H, Chu B, Takaya N, Cai J, Kerwin WS, Xu D, Polissar NL, Neradilek B, Hamar WK, Maki J, Shaw DW, Buck RJ, Wyman B, Yuan C: Reader and platform reproducibility for quantitative assessment of carotid atherosclerotic plaque using 1.5T Siemens, philips, and general electric scanners. J Magn Reson Imaging. 2007, 26: 344-352.CrossRefPubMed
13.
go back to reference Richardson PD, Davies MJ, Born GV: Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques [see comments]. Lancet. 1989, 2: 941-944.CrossRefPubMed Richardson PD, Davies MJ, Born GV: Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques [see comments]. Lancet. 1989, 2: 941-944.CrossRefPubMed
14.
go back to reference Mann JM, Davies MJ: Vulnerable plaque. Relation of characteristics to degree of stenosis in human coronary arteries. Circulation. 1996, 94: 928-931.CrossRefPubMed Mann JM, Davies MJ: Vulnerable plaque. Relation of characteristics to degree of stenosis in human coronary arteries. Circulation. 1996, 94: 928-931.CrossRefPubMed
15.
go back to reference Lendon CL, Davies MJ, Born GV, Richardson PD: Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis. 1991, 87: 87-90.CrossRefPubMed Lendon CL, Davies MJ, Born GV, Richardson PD: Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis. 1991, 87: 87-90.CrossRefPubMed
16.
go back to reference Galis ZS, Sukhova GK, Kranzhofer R, Clark S, Libby P: Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A. 1995, 92: 402-406.CrossRefPubMedPubMedCentral Galis ZS, Sukhova GK, Kranzhofer R, Clark S, Libby P: Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A. 1995, 92: 402-406.CrossRefPubMedPubMedCentral
17.
go back to reference Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT: Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994, 90: 775-778.CrossRefPubMed Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT: Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994, 90: 775-778.CrossRefPubMed
18.
go back to reference Li AC, Glass CK: The macrophage foam cell as a target for therapeutic intervention. Nat Med. 2002, 8: 1235-1242.CrossRefPubMed Li AC, Glass CK: The macrophage foam cell as a target for therapeutic intervention. Nat Med. 2002, 8: 1235-1242.CrossRefPubMed
19.
go back to reference Zhao XQ, Kerwin WS: Utilizing imaging tools in lipidology: examining the potential of MRI for monitoring cholesterol therapy. Clin Lipidol. 2012, 7: 329-343.CrossRefPubMedPubMedCentral Zhao XQ, Kerwin WS: Utilizing imaging tools in lipidology: examining the potential of MRI for monitoring cholesterol therapy. Clin Lipidol. 2012, 7: 329-343.CrossRefPubMedPubMedCentral
20.
go back to reference Reis ED, Li J, Fayad ZA, Rong JX, Hansoty D, Aguinaldo JG, Fallon JT, Fisher EA: Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model. J Vasc Surg. 2001, 34: 541-547.CrossRefPubMed Reis ED, Li J, Fayad ZA, Rong JX, Hansoty D, Aguinaldo JG, Fallon JT, Fisher EA: Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model. J Vasc Surg. 2001, 34: 541-547.CrossRefPubMed
21.
go back to reference Williams JK, Sukhova GK, Herrington DM, Libby P: Pravastatin has cholesterol lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol. 1998, 31: 684-691.CrossRefPubMed Williams JK, Sukhova GK, Herrington DM, Libby P: Pravastatin has cholesterol lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol. 1998, 31: 684-691.CrossRefPubMed
22.
go back to reference Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J: Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell deathin human carotid plaques: implications for plaque stabilization. Circulation. 2001, 103: 926-933.CrossRefPubMed Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J: Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell deathin human carotid plaques: implications for plaque stabilization. Circulation. 2001, 103: 926-933.CrossRefPubMed
23.
go back to reference Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS: Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multi-center FDG-PET/CT Feasibility Study. J Am Coll Cardiol. 2013, 62: 909-917.CrossRefPubMed Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS: Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multi-center FDG-PET/CT Feasibility Study. J Am Coll Cardiol. 2013, 62: 909-917.CrossRefPubMed
24.
go back to reference Saam T, Cai JM, Cai YQ, An NY, Kampschulte A, Xu D, Kerwin WS, Takaya N, Polissar NL, Hatsukami TS, Yuan C: Carotid plaque composition differs between ethno-racial groups: an MRI pilot study comparing mainland Chinese and American Caucasian patients. Arterioscler Thromb Vasc Biol. 2005, 25: 611-616.CrossRefPubMed Saam T, Cai JM, Cai YQ, An NY, Kampschulte A, Xu D, Kerwin WS, Takaya N, Polissar NL, Hatsukami TS, Yuan C: Carotid plaque composition differs between ethno-racial groups: an MRI pilot study comparing mainland Chinese and American Caucasian patients. Arterioscler Thromb Vasc Biol. 2005, 25: 611-616.CrossRefPubMed
25.
go back to reference Kerwin WS, Oikawa M, Yuan C, Jarvik G, Hatsukami T: MR imaging of adventitial vasa vasorum in carotid atherosclerosis. Magn Reson Med. 2008, 59: 507-514.CrossRefPubMed Kerwin WS, Oikawa M, Yuan C, Jarvik G, Hatsukami T: MR imaging of adventitial vasa vasorum in carotid atherosclerosis. Magn Reson Med. 2008, 59: 507-514.CrossRefPubMed
26.
27.
go back to reference Takaya N, Yuan C, Chu B, Saam T, Underhill H, Cai J, Tran N, Polissar NL, Isaac C, Ferguson MS, Garden GA, Cramer SC, Maravilla KR, Hashimoto B, Hatsukami TS: Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI-initial results. Stroke. 2006, 37: 818-823.CrossRefPubMed Takaya N, Yuan C, Chu B, Saam T, Underhill H, Cai J, Tran N, Polissar NL, Isaac C, Ferguson MS, Garden GA, Cramer SC, Maravilla KR, Hashimoto B, Hatsukami TS: Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI-initial results. Stroke. 2006, 37: 818-823.CrossRefPubMed
28.
go back to reference Singh N, Moody AR, Gladstone DJ, Leung G, Ravikumar R, Zhan J, Maggisano R: Moderate carotid artery stenosis: MRI depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men. Radiology. 2009, 252: 502-508.CrossRefPubMed Singh N, Moody AR, Gladstone DJ, Leung G, Ravikumar R, Zhan J, Maggisano R: Moderate carotid artery stenosis: MRI depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men. Radiology. 2009, 252: 502-508.CrossRefPubMed
29.
go back to reference Altaf N, Daniels L, Morgan PS, Auer D, MacSweeney ST, Moody AR, Gladman JR: Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events. J Vasc Surg. 2008, 47: 337-342.CrossRefPubMed Altaf N, Daniels L, Morgan PS, Auer D, MacSweeney ST, Moody AR, Gladman JR: Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events. J Vasc Surg. 2008, 47: 337-342.CrossRefPubMed
30.
go back to reference Dong L, Underhill HR, Yu W, Ota H, Hatsukami TS, Gao TL, Zhang Z, Oikawa M, Zhao X, Yuan C: Geometric and compositional appearance of atheroma in an angiographically normal carotid artery in patients with atherosclerosis. AJNR Am J Neuroradiol. 2010, 31: 311-316.CrossRefPubMed Dong L, Underhill HR, Yu W, Ota H, Hatsukami TS, Gao TL, Zhang Z, Oikawa M, Zhao X, Yuan C: Geometric and compositional appearance of atheroma in an angiographically normal carotid artery in patients with atherosclerosis. AJNR Am J Neuroradiol. 2010, 31: 311-316.CrossRefPubMed
31.
go back to reference Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H: Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation. 2004, 110: 1061-1068.CrossRefPubMed Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H: Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation. 2004, 110: 1061-1068.CrossRefPubMed
32.
go back to reference Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM, ASTEROID Investigators: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006, 295: 1556-1565.CrossRefPubMed Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM, ASTEROID Investigators: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006, 295: 1556-1565.CrossRefPubMed
Metadata
Title
Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin
Authors
Ruixue Du
Jianming Cai
Xue-Qiao Zhao
Qing-Jun Wang
Dan-Qing Liu
Wen-Xiu Leng
Peng Gao
Hong-Mei Wu
Lin Ma
Ping Ye
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2014
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/1471-2261-14-83

Other articles of this Issue 1/2014

BMC Cardiovascular Disorders 1/2014 Go to the issue