Abstract
ObjectiveAdvanced glycation end products (AGEs) have pathophysiological implications in cardiovascular diseases. The aim of our study was to evaluate the prognostic value of fluorescent AGEs and its soluble receptor (sRAGE) in the context of acute coronary syndrome (ACS), both in-hospital phase and follow-up period.MethodsA prospective clinical study was performed in patients with debut’s ACS. The endpoints were the development of cardiac events (cardiac deaths, re-infarction and new-onset heart failure) during in-hospital phase and follow-up period (366 days, inter-quartile range: 273–519 days). 215 consecutive ACS patients admitted to the coronary care unit (62.7±13.0 years, 24.2% female) were included. 47.4% had a diagnosis of ST segment elevation myocardial infarction. AGEs and sRAGE were analysed by fluorescence spectroscopy and competitive ELISA, respectively. Risk scores (GRACE, TIMI, PURSUIT) were calculated retrospectively using prospective data. The complexity of coronary artery disease was evaluated by SYNTAX score.ResultsThe mean fluorescent AGEs and sRAGE levels were 57.7±45.1 AU and 1045.4±850.0 pg/mL, respectively. 19 patients presented cardiac events during in-hospital phase and 29 during the follow-up. In-hospital cardiac events were significantly associated with higher sRAGE levels (p = 0.001), but not long-term cardiac events (p = 0.365). Regarding fluorescent AGE the opposite happened. After multivariate analysis correcting by gender, left ventricular ejection fraction, glucose levels, haemoglobin, GRACE and SYNTAX scores, sRAGE was significantly associated with in-hospital prognosis, whereas fluorescent AGEs was significantly associated with long-term prognosis.ConclusionsWe conclude that elevated values of sRAGE are associated with worse in-hospital prognosis, whereas high fluorescent AGE levels are associated with more follow-up events.
Highlights
Reducing sugars can react non-enzymatically with the amino groups of protein to form Amadori products
Glycation Products and acute coronary syndrome (ACS) There were no significant differences in fluorescent advanced glycation end products (AGEs) and soluble form of RAGE (sRAGE) plasma levels among the different ACS subtypes (Figure 2) (AGE = 48.7 (41.7–52.6), 45.5 (32.0–62.2) and 42.5 (33.7–51.0) arbitrary units (AU) vs. sRAGE = 836.7 (438.0–1308.5), 988.0 (602.2–1290.0) and 777.0 (517.3–1118.0) pg/mL, p.0.05, for UA, NSTEMI and STEMI, respectively), the percentage of NST-ACS patients (NSTEMI and UA) were higher in the higher quartiles of fluorescent AGEs (Table 2)
To predict in-hospital events, we found that the area under the curve (AUC) of sRAGE was 0.84
Summary
Reducing sugars can react non-enzymatically with the amino groups of protein to form Amadori products These early glycation products undergo further complex reaction such as rearrangement, dehydration, and condensation to become irreversibly crosslinked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs) [1]. The role of AGEsRAGE interaction is deemed of great importance in diabetic vasculopathy, a growing body of evidence indicates that this signalling pathway can play a role in non-diabetic atherosclerosis [3] This hypothesis has been tested in rodent models of exaggerated neointimal expansion – a hallmark of coronary stenosis – which is triggered by chronic hyperglycaemia or oxidative stress; and provided the first clue that RAGE-dependent mechanisms of inflammatory and tissue perturbation were not limited to the diabetic state [4]. Blockade of RAGE significantly decreased vascular expression of adhesion molecules, pro-thrombotic species as tissue factor, and diminished antigen activity of matrix metalloproteinases [5,6]
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