What is the clinical evidence from this study?

Study design: Cohort. Population: Acute Coronary Syndrome (n=208). Intervention: Pitavastatin vs. Atorvastatin 20 mg/day. Primary outcome: Plaque progression (percent change in plaque volume ≥0%) (OR 1.21, 95% CI 1.01-1.48, p=0.044).

What does this research mean for the field?

High baseline levels of advanced glycation end products are significantly associated with coronary plaque progression in patients with acute coronary syndrome, independent of diabetes mellitus. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research investigates how advanced glycation end products influence plaque progression in patients with acute coronary syndrome.

April 1, 20260 citationsOpen Access

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

正山正和山岸 YFYoshifumi Fukushima HDHiroyuki Daida

Key Result

High baseline levels of advanced glycation end products were significantly associated with coronary plaque progression (OR 1.21) in patients with acute coronary syndrome, independent of diabetes mellitus.

Key Points

This research investigates how advanced glycation end products influence plaque progression in patients with acute coronary syndrome.
Conducted intravascular ultrasound-guided percutaneous coronary intervention in patients with acute coronary syndrome.
Measured plaque volume and serum levels of advanced glycation end products and soluble RAGE at baseline and after treatment.
Compared changes in plaque volume with changes in serum levels of AGEs and sRAGE.
Statin therapy significantly reduced AGE levels from 8.6 to 8.0 U/ml (p < 0.001).
No significant change in sRAGE levels was observed.
High baseline AGEs levels were significantly associated with plaque progression, with an odds ratio of 1.21.

Study Design

Type

Cohort (n=208)

Blinding

Open-label, blind endpoint evaluation

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does baseline advanced glycation end products (AGEs) level predict coronary plaque progression in patients with acute coronary syndrome receiving statin therapy?

Population

Patients with acute coronary syndrome (ACS) who underwent successful intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI)

Intervention

Early aggressive statin therapy (pitavastatin 4 mg/day or atorvastatin 20 mg/day)

Outcome

Association between serum levels of advanced glycation end products (AGEs) and soluble RAGE (sRAGE) and percent change in coronary plaque volume (PV)surrogate

High baseline levels of advanced glycation end products (AGEs) independently predict coronary plaque progression in ACS patients on statin therapy, suggesting a role for cumulative oxidative stress in atherosclerosis.

Main Result

Effect estimate: OR 1.21 (95% CI 1.01-1.48)

p-value: p=0.044

Limitations

AGEs and sRAGE levels were measured in only 208 frozen samples, accounting for two-thirds of all participants.
The end point of the JAPAN-ACS trial was the change in total atheroma volume, which may not be affected by the AGE-RAGE axis.
The small number of patients with plaque progression limited the number of potential confounders that could be included in the multivariate model.

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. © 2013 Fukushima et al.; licensee BioMed Central Ltd.

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