Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2013

Open Access 01-12-2013 | Original investigation

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

Authors: 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, JAPAN-ACS Investigators

Published in: Cardiovascular Diabetology | Issue 1/2013

Login to get access

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
Appendix
Available only for authorised users
Literature
1.
Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG: American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). J Am Coll Cardiol. 2001, 37: 1478-1492. 10.1016/S0735-1097(01)01175-5.CrossRefPubMed
2.
von Birgelen C, Hartmann M, Mintz GS, van Houwelingen KG, Deppermann N, Schmermund A, Böse D, Eggebrecht H, Neumann T, Gössl M, Wieneke H, Erbel R: Relationship between cardiovascular risk as predicted by established risk scores versus plaque progression as measured by serial intravascular ultrasound in left main coronary arteries. Circulation. 2004, 110: 1579-1585. 10.1161/01.CIR.0000142048.94084.CA.CrossRefPubMed
3.
Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN, REVERSAL Investigators: Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004, 291: 1071-1080. 10.1001/jama.291.9.1071.CrossRefPubMed
4.
Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM, ASTEROID Investigators: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006, 295: 1556-1565. 10.1001/jama.295.13.jpc60002.CrossRefPubMed
5.
Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H: Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation. 2004, 110: 1061-1068. 10.1161/01.CIR.0000140261.58966.A4.CrossRefPubMed
6.
Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE: Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011, 365: 2078-2087. 10.1056/NEJMoa1110874.CrossRefPubMed
7.
Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M, JAPAN-ACS Investigators: Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study). J Am Coll Cardiol. 2009, 54: 293-302. 10.1016/j.jacc.2009.04.033.CrossRefPubMed
8.
Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M, JAPAN-ACS Investigators: Diabetes mellitus is a major negative determinant of coronary plaque regression during statin therapy in patients with acute coronary syndrome-serial intravascular ultrasound observations from the Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome Trial (the JAPAN-ACS Trial)-. Circ J. 2010, 74: 1165-1174. 10.1253/circj.CJ-09-0766.CrossRefPubMed
9.
Daida H, Takayama T, Hiro T, Yamagishi M, Hirayama A, Saito S, Yamaguchi T, Matsuzaki M, for the COSMOS Investigators: High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: Results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS). Cardiovasc Diabetol. 2012, 11: 87-10.1186/1475-2840-11-87.PubMedCentralCrossRefPubMed
10.
Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, Schoenhagen P, Nissen SE: Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol. 2008, 52: 255-262. 10.1016/j.jacc.2008.03.051.CrossRefPubMed
11.
Arai H, Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M, JAPAN-ACS Investigators: More intensive lipid lowering is associated with regression of coronary atherosclerosis in diabetic patients with acute coronary syndrome-sub-analysis of JAPAN-ACS study-. J Atheroscler Thromb. 2010, 17: 1096-1107. 10.5551/jat.5660.CrossRefPubMed
12.
An X, Yu D, Zhang R, Zhu J, Du R, Shi Y, Xiong X: Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: a one-year follow-up study. Cardiovasc Diabetol. 2012, 11: 71-10.1186/1475-2840-11-71.PubMedCentralCrossRefPubMed
13.
Herder M, Arntzen KA, Johnsen SH, Mathiesen EB: The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromso study. Cardiovasc Diabetol. 2012, 11: 77-10.1186/1475-2840-11-77.PubMedCentralCrossRefPubMed
14.
Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature. 2001, 414: 813-820. 10.1038/414813a.CrossRefPubMed
15.
Yamagishi S: Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes. Exp Gerontol. 2011, 46: 217-224. 10.1016/j.exger.2010.11.007.CrossRefPubMed
16.
Vlassara H, Palace MR: Diabetes and advanced glycation endproducts. J Intern Med. 2002, 251: 87-101. 10.1046/j.1365-2796.2002.00932.x.CrossRefPubMed
17.
Jandeleit-Dahm K, Cooper ME: The role of AGEs in cardiovascular disease. Curr Pharm Des. 2008, 14: 979-986. 10.2174/138161208784139684.CrossRefPubMed
18.
Basta G, Turco SD, Navarra T, Mazzarisi A, Cocci F, Coceani M, Bianchi M, Schlueter M, Marraccini P: Inverse Association between Circulating Levels of Soluble Receptor for Advanced Glycation End-Products and Coronary Plaque Burden. J Atheroscler Thromb. 2012, 19: 941-948. 10.5551/jat.10561.PubMed
19.
Peng WH, Lu L, Hu J, Yan XX, Zhang Q, Zhang RY, Chen QJ, Shen WF: Decreased serum esRAGE level is associated with angiographically determined coronary plaque progression in diabetic patients. Clin Biochem. 2009, 42: 1252-1259. 10.1016/j.clinbiochem.2009.04.017.CrossRefPubMed
20.
Takeuchi M, Makita Z, Bucala R, Suzuki T, Koike T, Kameda Y: Immunological evidence that non-carboxymethyllysine advanced glycation end-products are produced from short chain sugars and dicarbonyl compounds in vivo. Mol Med. 2000, 6: 114-125.PubMedCentralPubMed
21.
The Committee of Japan Diabetes Society on the diagnostic criteria of diabetes mellitus: Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. J Jpn Diabetes Soc. 2010, 53: 450-467.
22.
Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972, 18: 499-502.PubMed
23.
Hyogo H, Yamagishi S, Iwamoto K, Arihiro K, Takeuchi M, Sato T, Ochi H, Nonaka M, Nabeshima Y, Inoue M, Ishitobi T, Chayama K, Tazuma S: Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2007, 22: 1112-1119. 10.1111/j.1440-1746.2007.04943.x.CrossRefPubMed
24.
Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Ueda Y, Suzuki T, Yamada S, Takeuchi M, Fukami K, Ueda S, Adachi H, Matsui T, Okuda S, Yamagishi S: Positive association of serum levels of advanced glycation end products and high mobility group box-1 with asymmetric dimethylarginine in nondiabetic chronic kidney disease patients. Metabolism. 2009, 58: 1624-1628. 10.1016/j.metabol.2009.05.018.CrossRefPubMed
25.
Tahara N, Yamagishi SI, Matsui T, Takeuchi M, Nitta Y, Kodama N, Mizoguchi M, Imaizumi T: Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in nondiabetic subjects. Cardiovasc Ther. 2012 Feb, 30: 42-48. 10.1111/j.1755-5922.2010.00177.x.CrossRefPubMed
26.
Maeda S, Matsui T, Takeuchi M, Yoshida Y, Yamakawa R, Fukami K, Yamagishi S: Pigment epithelium-derived factor (PEDF) inhibits proximal tubular cell injury in early diabetic nephropathy by suppressing advanced glycation end products (AGEs)-receptor (RAGE) axis. Pharmacol Res. 2011, 63: 241-248. 10.1016/j.phrs.2010.11.008.CrossRefPubMed
27.
Wautier JL, Schmidt AM: Protein glycation: a firm link to endothelial cell dysfunction. Circ Res. 2004, 95: 233-238. 10.1161/01.RES.0000137876.28454.64.CrossRefPubMed
28.
Candido R, Forbes JM, Thomas MC, Thallas V, Dean RG, Burns WC, Tikellis C, Ritchie RH, Twigg SM, Cooper ME, Burrell LM: A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res. 2003, 92: 785-792. 10.1161/01.RES.0000065620.39919.20.CrossRefPubMed
29.
Soro-Paavonen A, Watson AM, Li J, Paavonen K, Koitka A, Calkin AC, Barit D, Coughlan MT, Drew BG, Lancaster GI, Thomas M, Forbes JM, Nawroth PP, Bierhaus A, Cooper ME, Jandeleit-Dahm KA: Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes. 2008, 57: 2461-2469. 10.2337/db07-1808.PubMedCentralCrossRefPubMed
30.
Bucciarelli LG, Kaneko M, Ananthakrishnan R, Harja E, Lee LK, Hwang YC, Lerner S, Bakr S, Li Q, Lu Y, Song F, Qu W, Gomez T, Zou YS, Yan SF, Schmidt AM, Ramasamy R: Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation. 2006, 113: 1226-1234. 10.1161/CIRCULATIONAHA.105.575993.CrossRefPubMed
31.
Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, O'Leary DH, Genuth S, Diabetes Control and Complications Trial Epidemiology of Diabetes Interventions and Complications Research Group Diabetes Control and Complications Trial Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med. 2003, 348: 2294-2303.CrossRefPubMed
32.
Yamagishi S, Matsui T, Nakamura K: Possible involvement of tobacco-derived advanced glycation end products (AGEs) in an increased risk for developing cancers and cardiovascular disease in former smokers. Med Hypotheses. 2008, 71: 259-261. 10.1016/j.mehy.2008.03.020.CrossRefPubMed
33.
Zhang Y, Luo Z, Ma L, Xu Q, Yang Q, Si L: Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor gamma activation. Int J Mol Med. 2010, 25: 729-734.CrossRefPubMed
34.
Tekabe Y, Luma J, Einstein AJ, Sedlar M, Li Q, Schmidt AM, Johnson LL: A novel monoclonal antibody for RAGE-directed imaging identifies accelerated atherosclerosis in diabetes. J Nucl Med. 2010, 51: 92-97. 10.2967/jnumed.109.064659.CrossRefPubMed
Metadata
Title
Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome: The JAPAN-ACS Sub-study
Authors
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
JAPAN-ACS Investigators
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-12-5

Other articles of this Issue 1/2013

Cardiovascular Diabetology 1/2013 Go to the issue

Original investigation

Blood glucose may be an alternative to cholesterol in CVD risk prediction charts

Original investigation

Protein kinase RNA- like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)- mediated endoplasmic reticulum stress- induced apoptosis in diabetic cardiomyopathy

Original investigation

20/(fasting C-peptide × fasting plasma glucose) is a simple and effective index of insulin resistance in patients with type 2 diabetes mellitus: a preliminary report

Original investigation

Inverse associations between light-to-moderate alcohol intake and lipid-related indices in patients with diabetes

Original investigation

Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

Original investigation

Cardiovascular risk escalation with caloric excess: a prospective demonstration of the mechanics in healthy adults
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits