This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.03.069v1 48/9/1825    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tahara, N. Articles by Imaizumi, T. Search for Related Content PubMed PubMed Citation Articles by Tahara, N. Articles by Imaizumi, T. Related Collections Related Article

CLINICAL RESEARCH

Simvastatin Attenuates Plaque Inflammation

Evaluation by Fluorodeoxyglucose Positron Emission Tomography

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

^_* Department of Medicine/Cardiovascular Research Institute, Division of Cardio-Vascular Medicine
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

Related Article

In Vivo ¹⁸ F-Fluorodeoxyglucose Positron Emission Tomography Imaging Provides a Noninvasive Measure of Carotid Plaque Inflammation in Patients

Ahmed Tawakol, Raymond Q. Migrino, Gregory G. Bashian, Shahinaz Bedri, David Vermylen, Ricardo C. Cury, Denise Yates, Glenn M. LaMuraglia, Karen Furie, Stuart Houser, Henry Gewirtz, James E. Muller, Thomas J. Brady, and Alan J. Fischman
J. Am. Coll. Cardiol. 2006 48: 1818-1824. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				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]

				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]

				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]

				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]

				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]

				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]

				J. Sanz, P. R. Moreno, and V. Fuster The year in atherothrombosis. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 944 - 955. [Full Text] [PDF]

				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. [Full Text] [PDF]

				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]

				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. [Full Text] [PDF]

				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]

				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]

				F. A. Jaffer, P. Libby, and R. Weissleder Molecular Imaging of Cardiovascular Disease Circulation, August 28, 2007; 116(9): 1052 - 1061. [Full Text] [PDF]

				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]

				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. [Full Text] [PDF]

				H. Kai, N. Tahara, M. Ishibashi, and T. Imaizumi Reply J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1991 - 1992. [Full Text] [PDF]

				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]