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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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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]



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