Fluorescent Advanced Glycation End Products and Their Soluble Receptor: The Birth of New Plasmatic Biomarkers for Risk Stratification of Acute Coronary Syndrome

Objective: Advanced 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. Methods: A 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. Results: The 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. Conclusions: We 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

Predictive value of advanced glycation end products for the development of post-infarction heart failure: a preliminary report

Abstract Background Since post-infarction heart failure (HF) determines a great morbidity and mortality, and given the physiopathology implications of advanced glycation end products (AGE) in the genesis of myocardial dysfunction, it was intended to analyze the prognostic value of these molecules in order to predict post-infarction HF development. Methods A prospective clinical study in patients after first acute coronary syndrome was conducted. The follow-up period was consisted in 1 year. In 194 patients consecutively admitted in the coronary unit for myocardial infarct fluorescent AGE levels were measured. The association between glycaemic parameters and the development of post-infarction HF were analyzed in those patients. Finally, we identified the variables with independent predictor value by performing a multivariate analysis of Hazard ratio for Cox regression. Results Eleven out of 194 patients (5.6%) developed HF during follow-up (median: 1.0 years [0.8 - 1.5 years]). Even though basal glucose, fructosamine and glycated haemoglobin were significant predictive factors in the univariate analysis, after being adjusted by confounding variables and AGE they lost their statistical signification. Only AGE (Hazard Ratio 1.016, IC 95%: 1.006-1.026; p Conclusions AGE are an independent marker of post-infarction HF development risk.</p

Curves of sensitivity and specificity for fluorescent AGEs and sRAGE to predict events.

<p>A) representation of sRAGE curves to predict in-hospital events and B) fluorescent AGE curves to predict follow-up events.</p

Multiple regression analysis for in-hospital and follow-up events.

<p><b>LVEF</b>: Left Ventricular Ejection Fraction.</p

Clinical outcomes based on quartiles of sRAGE and fluorescent AGE.

<p>Clinical outcomes based on quartiles of sRAGE and fluorescent AGE.</p

Relation of fluorescent AGEs and sRAGE with the type of ACS.

<p>Box plots for fluorescent AGE (A) and sRAGE (B) plasma levels for non ST-segment elevation acute coronary syndrome patients (NST-ACS) and ST-segment elevation myocardial infarction (STEMI).</p

Baseline characteristics of study population, stratified by presence of in-hospital and follow-up cardiac events.

<p><b>ACEI/ARB II:</b> Angiotensin-converting Enzyme Inhibitors/Angiotensin II receptor blockers. <b>BMI</b>: Body Mass Index. <b>LVEF</b>: Left Ventricular Ejection Fraction. <b>PCI</b>: Percutaneous Coronary Intervention. <b>STEMI</b>: ST-elevation myocardial infarction. <b>UA</b>: Unstable Angina.</p

Relation of sRAGE levels and risk categories of different ACS scores.

<p>Columns represent mean values (indicated in numbers) for sRAGE plasma levels in each category of the indicated scores.</p

Baseline characteristics based on quartiles of fluorescent AGE.

<p>Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074302#pone-0074302-t001" target="_blank">table 1</a>.</p

Survival Kaplan Meier curves according fluorescent AGE quartiles.

<p>Inset represent curves magnifications about survival free of events.</p