Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome

The JAPAN-ACS Sub-study

Yoshifumi Fukushima, Hiroyuki Daida, Takeshi Morimoto, Takatoshi Kasai, Katsumi Miyauchi, Sho ichi Yamagishi, Masayoshi Takeuchi, Takafumi Hiro, Takeshi Kimura, Yoshihisa Nakagawa, Masakazu Yamagishi, Yukio Ozaki, Masunori Matsuzaki

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: 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.Methods: 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.Results: 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.Conclusions: 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: NCT00242944.

Original languageEnglish
Article number5
JournalCardiovascular Diabetology
Volume12
Issue number1
DOIs
Publication statusPublished - 07-01-2013

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Advanced Glycosylation End Products
Acute Coronary Syndrome
Diabetes Mellitus
Japan
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Percutaneous Coronary Intervention
Logistic Models
Oxidative Stress
Therapeutics
Odds Ratio
Atorvastatin Calcium
pitavastatin
Confidence Intervals
Glucose
Serum
Advanced Glycosylation End Product-Specific Receptor

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Fukushima, Yoshifumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Kasai, Takatoshi ; Miyauchi, Katsumi ; Yamagishi, Sho ichi ; Takeuchi, Masayoshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Matsuzaki, Masunori. / Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome : The JAPAN-ACS Sub-study. In: Cardiovascular Diabetology. 2013 ; Vol. 12, No. 1.
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abstract = "Background: 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.Methods: 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.Results: 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.Conclusions: 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: NCT00242944.",
author = "Yoshifumi Fukushima and Hiroyuki Daida and Takeshi Morimoto and Takatoshi Kasai and Katsumi Miyauchi and Yamagishi, {Sho ichi} and Masayoshi Takeuchi and Takafumi Hiro and Takeshi Kimura and Yoshihisa Nakagawa and Masakazu Yamagishi and Yukio Ozaki and Masunori Matsuzaki",
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Fukushima, Y, Daida, H, Morimoto, T, Kasai, T, Miyauchi, K, Yamagishi, SI, Takeuchi, M, Hiro, T, Kimura, T, Nakagawa, Y, Yamagishi, M, Ozaki, Y & Matsuzaki, M 2013, 'Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome: The JAPAN-ACS Sub-study', Cardiovascular Diabetology, vol. 12, no. 1, 5. https://doi.org/10.1186/1475-2840-12-5

Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome : The JAPAN-ACS Sub-study. / Fukushima, Yoshifumi; Daida, Hiroyuki; Morimoto, Takeshi; Kasai, Takatoshi; Miyauchi, Katsumi; Yamagishi, Sho ichi; Takeuchi, Masayoshi; Hiro, Takafumi; Kimura, Takeshi; Nakagawa, Yoshihisa; Yamagishi, Masakazu; Ozaki, Yukio; Matsuzaki, Masunori.

In: Cardiovascular Diabetology, Vol. 12, No. 1, 5, 07.01.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome

T2 - The JAPAN-ACS Sub-study

AU - Fukushima, Yoshifumi

AU - Daida, Hiroyuki

AU - Morimoto, Takeshi

AU - Kasai, Takatoshi

AU - Miyauchi, Katsumi

AU - Yamagishi, Sho ichi

AU - Takeuchi, Masayoshi

AU - Hiro, Takafumi

AU - Kimura, Takeshi

AU - Nakagawa, Yoshihisa

AU - Yamagishi, Masakazu

AU - Ozaki, Yukio

AU - Matsuzaki, Masunori

PY - 2013/1/7

Y1 - 2013/1/7

N2 - Background: 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.Methods: 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.Results: 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.Conclusions: 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: NCT00242944.

AB - Background: 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.Methods: 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.Results: 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.Conclusions: 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: NCT00242944.

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