Abstract

The aim of this study was to explore the possible association between markers of inflammation and oxidative stress (OS) and markers of cardiac function and necrosis in 100 NSTEMI (non-ST-elevation myocardial infarction) patients with various degrees of kidney dysfunction. At admission, ejection fraction (EF), brain natriuretic peptide (BNP), troponin (TnI), creatinine phosphokinase (CPK), alanine transaminase (ALT), aspartate transaminase (AST), high-sensitive C-reactive protein (hs-CRP), interleukins 6 and 10 (IL-6, IL10), myeloperoxidase (MPO), transforming growth factor beta (TGF-β1), glomerular filtration rate (GFR), and albuminuria were assessed. Study participants were divided into 2 subgroups based on the median level of EF. Compared to the high, patients in the low EF group had higher GFR, BNP, CPK, hs-CRP, IL-10, IL-6, and MPO values and lower albuminuria levels. The levels of EF decreased in parallel with the progression of CKD, whereas the levels of BNP, IL-6, and TGF-β were significantly higher in late stages of CKD. Spearman's rho correlation analysis showed that EF was inversely correlated with MPO (r = −0.20, p = 0.05) BNP (r = −0.30, p = 0.002), hs-CRP (r = −0.38, p < 0.0001), IL-10 (r = −0.30, p = 0.003), and IL-6 (r = −0.24, p = 0.02) and positively with GFR (r = 0.27, p = 0.008). TnI was correlated with CPK (r = 0.44, p < 0.0001), CPK-MB (r = 0.31, p = 0.002), ALT (r = 0.50, p < 0.0001), AST (r = 0.29, p = 0.004), IL-10 (r = 0.22, p = 0.03), and MPO (r = −0.28, p = 0.006). In multivariate regression analysis, only BNP (β = −0.011, p = 0.004), hs-CRP (β = −0.11, p = 0.001), and GFR (β = 0.12, p = 0.0029) were independent determinants of EF. Similarly, MPO (β = −1.69, p = 0.02), IL-10 (β = 0.15, p = 0.006), and AST (β = 0.04, p = 0.001) were the 3 major determinants of TnI. Based on these associations, we built a predictive model including markers of inflammation and OS (MPO, IL-10, and hs-CRP) to identify patients with the most severe cardiac injury (combined EF below median and troponin above median values). Receiver-operator characteristic (ROC) analysis showed that the area under the ROC curve of this model to detect patients with low EF and high TnI was 0.67 (p = 0.015, 95%confidence interval = 0.53‐0.81).

Highlights

  • Acute coronary syndrome (ACS), one of the most common manifestations of atherosclerosis, is caused by the rupture or erosion of unstable atherosclerotic plaque

  • The aim of this study was to explore the possible association between markers of inflammation and oxidative stress (OS) and markers of cardiac function and necrosis in 100 non-ST-elevation myocardial infarction (NSTEMI) patients with various degrees of kidney dysfunction

  • In-hospital mortality is higher in patients with STsegment elevation myocardial infarction (STEMI) compared to non-ST-elevation myocardial infarction (NSTEMI) at the time of admission, the 6-month mortality rates are similar in both entities

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Summary

Introduction

Acute coronary syndrome (ACS), one of the most common manifestations of atherosclerosis, is caused by the rupture or erosion of unstable atherosclerotic plaque. After 4 years of follow-up, compared to STEMI, NSTEMI patients have a twofold increase in overall mortality [3] This may be explained by the fact that patients with NSTEMIACS are older and suffer from more comorbidities, such as diabetes and chronic kidney disease (CKD), endothelial dysfunction, and inflammation [4]. Low-grade systemic inflammation and oxidative stress (OS) play a key role in the onset and development of atherosclerosis [5,6,7] These interrelated entities—which are significantly deranged in CKD—upregulate cytokines and growth factors resulting in endothelial damage and dysfunction, which is the hallmark of atherosclerosis [6]. In NSTEMIACS patients, inflammatory cytokines and markers are predictors of cardiovascular (CV) risk and OS amplifies this association This could be attributed to the fact that these molecules do not reflect inflammation solely, but may significantly contribute to plaque rupture [8]. Recent data show that MPO may represent a useful diagnostic and prognostic tool in patients with endothelial dysfunction and ACS [13], over a period of 30 days up to six months, even in patients with negative cardiac troponin T (TnT) values and in the absence of myocardial necrosis

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