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Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome: The JAPAN-ACS Sub-study

Yoshifumi Fukushima1, Hiroyuki Daida1*, Takeshi Morimoto2, Takatoshi Kasai1, Katsumi Miyauchi1, Sho-ichi Yamagishi3, Masayoshi Takeuchi4, Takafumi Hiro5, Takeshi Kimura6, Yoshihisa Nakagawa7, Masakazu Yamagishi8, Yukio Ozaki9, Masunori Matsuzaki10 and JAPAN-ACS Investigators

Author Affiliations

1 Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan

2 Center for General Internal Medicine and Emergency Care, Kinki University School of Medicine, Osakasayama, Japan

3 Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan

4 Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada, Japan

5 Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

6 Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

7 Department of Cardiology, Tenri Hospital, Nara, Japan

8 Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

9 Division of Cardiology, Fujita Health University, Toyoake, Japan

10 Yamaguchi University, Ube, Japan

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Cardiovascular Diabetology 2013, 12:5  doi:10.1186/1475-2840-12-5

Published: 7 January 2013



The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.


Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8–12 months after PCI.


At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.


High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.

Trial registration


Advanced glycation end products; Acute coronary syndrome; Intravascular ultrasound; Plaque; Statins