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J Am Coll Cardiol, 2006; 48:1825-1831, doi:10.1016/j.jacc.2006.03.069 (Published online 16 October 2006).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH

Simvastatin Attenuates Plaque Inflammation

Evaluation by Fluorodeoxyglucose Positron Emission Tomography

Nobuhiro Tahara, MD, PhD*, Hisashi Kai, MD, PhD*,*, Masatoshi Ishibashi, MD, PhD{dagger}, Hiroyuki Nakaura, MD, PhD*, Hayato Kaida, MD{dagger}, Kenkichi Baba, MD{dagger}, Naofumi Hayabuchi, MD, PhD{dagger} and Tsutomu Imaizumi, MD, PhD*

* Department of Medicine/Cardiovascular Research Institute, Division of Cardio-Vascular Medicine
{dagger} Department of Radiology, Kurume University School of Medicine, Kurume, Japan

Manuscript received January 10, 2006; revised manuscript received March 3, 2006, accepted March 6, 2006.

* Reprint requests and correspondence: Dr. Hisashi Kai, Department of Medicine/Cardiovascular Research Institute, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. (Email: naikai{at}med.kurume-u.ac.jp).

OBJECTIVES: We investigated whether simvastatin attenuates plaque inflammation by using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) co-registered with computerized tomography.

BACKGROUND: Inflammation plays a key role in progression and destabilization of atherosclerotic plaque. 18F-fluorodeoxyglucose PET is a promising tool for visualizing inflammation of atherosclerotic plaque. Antiinflammatory action is one of the pleiotropic effects of statins.

METHODS: Forty-three consecutive subjects, who underwent 18FDG-PET for cancer screening and had 18FDG uptakes in the thoracic aorta and/or the carotid arteries, were randomized to either statin group receiving simvastatin (n = 21) or diet group receiving dietary management only (n = 22). The maximum standardized uptake values (SUVs) were measured in individual plaques, and were averaged for analysis of the subjectwise results. The responses were assessed after 3-month treatments.

RESULTS: Positron emission tomography revealed 117 and 123 18FDG-positive plaques in the statin and diet groups, respectively. Simvastatin, but not diet alone, attenuated plaque 18FDG uptakes and decreased the SUVs (p < 0.01). Simvastatin reduced low-density lipoprotein cholesterol (LDL-C) by 30% (p < 0.01) and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01), whereas LDL-C and HDL-C levels were not changed in the diet group. In the statin group, the decrease in the SUV was well correlated with the HDL-C elevation (p < 0.01) but not with the LDL-C reduction.

CONCLUSIONS: 18F-fluorodeoxyglucose PET visualized plaque inflammation and simvastatin attenuated it. The LDL-C–independent effects of simvastatin may participate in the beneficial effect. 18F-fluorodeoxyglucose PET has a potential for visually monitoring plaque inflammation and the therapeutic effectiveness of statins.

Abbreviations and Acronyms
  18FDG = 18F-fluorodeoxyglucose
  CT = computed tomography
  HDL-C = high-density lipoprotein cholesterol
  hsCRP = high-sensitivity C-reactive protein
  LDL-C = low-density lipoprotein cholesterol
  MRI = magnetic resonance imaging
  PET = positron emission tomography


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J. Am. Coll. Cardiol. 2006 48: 1818-1824. [Abstract] [Full Text] [PDF]



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Relationships Among Regional Arterial Inflammation, Calcification, Risk Factors, and Biomarkers: A Prospective Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Imaging Study
Circ Cardiovasc Imaging, March 1, 2009; 2(2): 107 - 115.
[Abstract] [Full Text] [PDF]

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 J Am Coll Cardiol ImgHome page
E. A. Osborn and F. A. Jaffer
The year in molecular imaging.
J. Am. Coll. Cardiol. Img., January 1, 2009; 2(1): 97 - 113.
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 StrokeHome page
D. Izquierdo-Garcia, J. R. Davies, M. J. Graves, J. H.F. Rudd, J. H. Gillard, P. L. Weissberg, T. D. Fryer, and E. A. Warburton
Comparison of Methods for Magnetic Resonance-Guided [18-F]Fluorodeoxyglucose Positron Emission Tomography in Human Carotid Arteries: Reproducibility, Partial Volume Correction, and Correlation Between Methods
Stroke, January 1, 2009; 40(1): 86 - 93.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
S. Fujimoto, D. Hartung, S. Ohshima, D. S. Edwards, J. Zhou, P. Yalamanchili, M. Azure, A. Fujimoto, S. Isobe, Y. Matsumoto, et al.
Molecular Imaging of Matrix Metalloproteinase in Atherosclerotic Lesions: Resolution With Dietary Modification and Statin Therapy
J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1847 - 1857.
[Abstract] [Full Text] [PDF]

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 HeartHome page
H Kuehl, H Eggebrecht, T Boes, G Antoch, S Rosenbaum, S Ladd, A Bockisch, J Barkhausen, and R Erbel
Detection of inflammation in patients with acute aortic syndrome: comparison of FDG-PET/CT imaging and serological markers of inflammation
Heart, November 1, 2008; 94(11): 1472 - 1477.
[Abstract] [Full Text] [PDF]

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 JNMHome page
Y. Zhao, Y. Kuge, S. Zhao, H. W. Strauss, F. G. Blankenberg, and N. Tamaki
Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice
J. Nucl. Med., October 1, 2008; 49(10): 1707 - 1714.
[Abstract] [Full Text] [PDF]

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 JNMHome page
S. J. Lee, Y. K. On, E. J. Lee, J. Y. Choi, B.-T. Kim, and K.-H. Lee
Reversal of Vascular 18F-FDG Uptake with Plasma High-Density Lipoprotein Elevation by Atherogenic Risk Reduction
J. Nucl. Med., August 1, 2008; 49(8): 1277 - 1282.
[Abstract] [Full Text] [PDF]

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 JNMHome page
J. H.F. Rudd, K. S. Myers, S. Bansilal, J. Machac, C. A. Pinto, C. Tong, A. Rafique, R. Hargeaves, M. Farkouh, V. Fuster, et al.
Atherosclerosis Inflammation Imaging with 18F-FDG PET: Carotid, Iliac, and Femoral Uptake Reproducibility, Quantification Methods, and Recommendations
J. Nucl. Med., June 1, 2008; 49(6): 871 - 878.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
K. Aziz, K. Berger, K. Claycombe, R. Huang, R. Patel, and G. S. Abela
Noninvasive Detection and Localization of Vulnerable Plaque and Arterial Thrombosis With Computed Tomography Angiography/Positron Emission Tomography
Circulation, April 22, 2008; 117(16): 2061 - 2070.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. Sanz, P. R. Moreno, and V. Fuster
The Year in Atherothrombosis
J. Am. Coll. Cardiol., March 4, 2008; 51(9): 944 - 955.
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 JNMHome page
M. P. S. Dunphy, H. Schoder, and H. W. Strauss
Radionuclide Techniques for Identifying Vulnerable Plaque
J. Nucl. Med., November 1, 2007; 48(11): 1753 - 1755.
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 JNMHome page
D. Hartung, A. Petrov, N. Haider, S. Fujimoto, F. Blankenberg, A. Fujimoto, R. Virmani, F. D. Kolodgie, H. W. Strauss, and J. Narula
Radiolabeled Monocyte Chemotactic Protein 1 for the Detection of Inflammation in Experimental Atherosclerosis
J. Nucl. Med., November 1, 2007; 48(11): 1816 - 1821.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
R. J. Gibbons, P. A. Araoz, and E. E. Williamson
The Year in Cardiac Imaging
J. Am. Coll. Cardiol., September 4, 2007; 50(10): 988 - 1003.
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 Eur Heart JHome page
N. Tahara, H. Kai, H. Nakaura, M. Mizoguchi, M. Ishibashi, H. Kaida, K. Baba, N. Hayabuchi, and T. Imaizumi
The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose positron emission tomography
Eur. Heart J., September 2, 2007; 28(18): 2243 - 2248.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. H.F. Rudd, K. S. Myers, S. Bansilal, J. Machac, A. Rafique, M. Farkouh, V. Fuster, and Z. A. Fayad
18Fluorodeoxyglucose Positron Emission Tomography Imaging of Atherosclerotic Plaque Inflammation Is Highly Reproducible: Implications for Atherosclerosis Therapy Trials
J. Am. Coll. Cardiol., August 28, 2007; 50(9): 892 - 896.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
F. A. Jaffer, P. Libby, and R. Weissleder
Molecular Imaging of Cardiovascular Disease
Circulation, August 28, 2007; 116(9): 1052 - 1061.
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 Circ. Res.Home page
M. Koga, H. Kai, H. Yasukawa, T. Yamamoto, Y. Kawai, S. Kato, K. Kusaba, M. Kai, K. Egashira, Y. Kataoka, et al.
Inhibition of Progression and Stabilization of Plaques by Postnatal Interferon-{gamma} Function Blocking in ApoE-Knockout Mice
Circ. Res., August 17, 2007; 101(4): 348 - 356.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. H.F. Rudd, J. Machac, and Z. A. Fayad
Simvastatin and Plaque Inflammation
J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1991 - 1991.
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 J Am Coll CardiolHome page
H. Kai, N. Tahara, M. Ishibashi, and T. Imaizumi
Reply
J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1991 - 1992.
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 J Am Coll CardiolHome page
N. Tahara, H. Kai, S.-i. Yamagishi, M. Mizoguchi, H. Nakaura, M. Ishibashi, H. Kaida, K. Baba, N. Hayabuchi, and T. Imaizumi
Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose Positron Emission Tomography Is Associated With the Metabolic Syndrome
J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1533 - 1539.
[Abstract] [Full Text] [PDF]


 
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