Compartilhar
Informação da revista
Compartilhar
Compartilhar
Baixar PDF
Mais opções do artigo
Visitas
...
Original Article
DOI: 10.1016/j.repc.2020.08.010
Open Access
Disponível online o 31 Dezembro 2020
Predictive value of oxidant and antioxidant status for contrast-induced nephropathy after percutaneous coronary intervention for ST-segment elevation myocardial infarction
Valor preditivo dos estados oxidante e antioxidante na nefropatia de contraste após intervenção coronária percutânea em enfarte do miocárdio com elevação do segmento ST
Visitas
...
Fatih Aksoya,
Autor para correspondência
dr.aksoy@hotmail.com

Corresponding author.
, Hasan Aydın Başb, Ali Bağcıa, Hasan Basri Savaşc
a Suleyman Demirel University, Faculty of Medicine, Cardiology Department, Turkey
b Isparta City Hospital, Cardiology Department, Turkey
c Alanya Alaaddin Keykubat University, Turkey
Recebido 27 Outubro 2019. Aceite 25 Agosto 2020
Informação do artigo
Resume
Texto Completo
Bibliografia
Baixar PDF
Estatísticas
Figuras (1)
Tabelas (5)
Table 1. Demographic and clinical characteristics of patients with and without contrast-induced nephropathy.
Table 2. Comparison of plasma oxidative stress and inflammation parameters in patients with and without contrast-induced nephropathy.
Table 3. Univariate and multivariate regression analyses of predictors of contrast-induced nephropathy in the study population.
Table 4. Receiver operating characteristics curve analysis of oxidative parameters.
Table 5. Correlation analysis of study variables.
Mostrar maisMostrar menos
Abstract
Background

Contrast-induced nephropathy (CIN) is a life-threatening complication after primary percutaneous coronary intervention (p-PCI). Oxidative stress and inflammation may play an important role in the development of CIN.

Objective

We aimed to assess the relationship between total oxidant status, total antioxidant capacity, high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase and uric acid (UA) in the development of CIN in patients presenting with ST-elevation myocardial infarction (STEMI).

Methods

This prospective cohort study consisted of 341 patients with STEMI. Patients were divided into two groups: those with and those without CIN. Predictors of CIN were determined by multivariate regression analyses.

Results

Multivariate regression analysis showed that initial glucose level, contrast media volume/glomerular filtration ratio (eGFR) ratio, hs-CRP, UA and oxidative status index were associated with the development of CIN in patients with STEMI.

Conclusion

The main finding of this study is that increased oxidative stress and inflammation parameters were associated with the development of CIN in patients with STEMI. Other independent predictors of CIN were contrast media volume/eGFR ratio, initial glucose level, UA and hs-CRP.

Keywords:
Contrast-induced nephropathy
Oxidant and antioxidant status
ST-segment elevation myocardial infarction
Resumo
Contexto

A nefropatia induzida por contraste (NIC) é uma complicação crítica após intervenção coronária percutânea primária (ICP-p). O stress oxidativo e a inflamação podem ter um papel importante no desenvolvimento da NIC.

Objetivo

Avaliar a associação entre o estado oxidante total (EOT), a capacidade total (COT), a proteína C-reativa de alta sensibilidade (PCR-as), a gama glutamiltransferase (GGT) e o ácido úrico (AU) no desenvolvimento de doentes com NIC que se apresentam com STEMI.

Métodos

Este estudo de coorte prospetivo incluiu 341 doentes com enfarte do miocárdio com elevação do segmento ST (STEMI). Os doentes foram divididos em dois grupos: os portadores e os não portadores de NIC. Os valores preditivos de NIC foram determinados por análises de regressão multivariada.

Resultados

A análise de regressão multivariada demonstrou que o nível inicial de glicose, o volume dos meios de contraste/taxa de filtração glomerular estimada (TFGe), a PCR-as e o índice do estado oxidativo foram associados ao desenvolvimento da NIC em doentes com STEMI.

Conclusão

O aumento do stress oxidativo e dos parâmetros inflamatórios estão associados ao desenvolvimento da NIC em doentes com STEMI. Outros fatores preditivos independentes da NIC foram o volume dos meios de contraste/TFG, o nível daglicemia inicial, o AU e a PCR-as.

Palavras-chave:
Nefropatia induzida por contraste
Estados oxidante e antioxidante
Enfarte do miocárdio com elevação do segmento ST
Texto Completo
Significance of the study

Contrast-induced nephropathy (CIN) is a rare but life-threatening complication of primary percutaneous coronary interventions (pPCI). Preventing the development of CIN is very important for decreased mortality and morbidity after p-PCI. Our study demonstrated that oxidative parameters such as gamma-glutamyltransferase, 4 (UA), total oxidant status and total antioxidant status, as well as inflammatory parameters such as C-reactive protein could be useful prognostic biomarkers in acute myocardial infarction (AMI). Additionally, measurement of the oxidative status may be useful in preventing the development of CIN after pPCI.

Introduction

Primary percutaneous coronary intervention (p-PCI) is the recommended reperfusion strategy for patients who present acute ST-elevation myocardial infarction (STEMI) within the first few hours after the onset of symptoms.1 However, some life-threatening complications such as contrast-induced nephropathy (CIN) are observed after p-PCI.2,3 Evidence shows a strong correlation between CIN and high mortality and morbidity in patients with STEMI.2 Additionally, these patients tend to be hospitalized for long periods.2 Several clinical and laboratory variables have been associated with the development of CIN, including contrast media volume, presence of diabetes mellitus, chronic congestive heart failure, anemia and decreased renal perfusion.3 Production of reactive oxygen species (ROS) and impaired renal perfusion are the two major mechanisms involved in the pathogenesis of CIN.4,5 In addition, previous studies have suggested that CIN may lead to a decrease in the activity of antioxidant enzymes and cause cytotoxic effects via the release of ROS. Increased reactive oxygen radicals may cause an increase in renal medullary hypoxia.4–6 Additionally, antioxidant supplements such as ascorbic acid and drugs such as N-acetylcysteine (NAC) could lead to the amelioration of CIN.7,8 Although many studies have shown alterations in total oxidant status and antioxidant capacity in various diseases, including end-stage renal disease, atrial fibrillation and hypertension, to the best of our knowledge, none have examined these parameters in predicting CIN in patients with STEMI.9–11

In a clinical setting, serum creatinine level is generally used as a marker of renal function, even though this marker is affected by several factors such as age, gender, muscle mass, weight, and ethnicity.12,13 Additionally, serum creatinine is not a marker of renal damage per se and is elevated only at advanced stages of renal disease. For these reasons, use of serum creatinine as a marker could lead to under-estimation of CIN.13 Patients at high risk of CIN should undergo early prophylactic measures such as hydration and the antioxidant NAC to prevent CIN.8 Additionally, high risk patients should be followed up for progression of serum creatinine levels after the procedure.2 Therefore, there is a need for the development of new laboratory parameters to predict the development of CIN. In this study, we aimed to assess the association between total oxidant status (TOS), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT) and uric acid (UA) in the development of CIN in patients presenting with STEMI.

Material and methodsStudy population

In this prospective single-center study, 341 patients undergoing primary percutaneous coronary intervention (p-PCI) for diagnosis of STEMI were screened between June 2012 and July 2019. Exclusion criteria included hyperthyroidism (six patients), age <18-years, end-stage renal failure (15 patients), patients treated with emergent coronary artery bypass graft surgery (five patients), sepsis (five patients), exposure to contrast injection in the seven days prior to p-PCI (10 patients), known malignancy, severe hepatic dysfunction, and inflammatory disease. Patients who presented with cardiogenic shock or died during the first 72 hours of their hospital stay or during revascularization were also excluded from the study. The final study cohort consisted of 300 patients with STEMI. The study protocol was reviewed and approved by the local ethics committee in accordance with the Declaration of Helsinki. All participants provided written informed consent.

All p-PCIs were performed via the femoral artery by an experienced interventional cardiologist using the appropriate equipment (Toshiba Medical Systems, Nasushiobara, Japan). Non-ionic low osmolality contrast medium (Omnipaque 350 MG/ml; GE Healthcare, Cork, Ireland) was used for the p-PCIs and the total contrast medium volume used was recorded for all patients. All patients were administered 300 mg acetylsalicylic acid (ASA) with a loading dose of 300 mg clopidogrel before the procedure. A dose of 70–100 U/kg unfractionated heparin was administered after visualizing arterial anatomy. The use of bare metal or drug-eluting stents and glycoprotein IIb/IIIa was at the discretion of the physician. All of the patients received intravenous hydration with isotonic saline and were transferred to the intensive care unit (ICU) after the procedure, where treatment was continued with 100 mg ASA and 75 mg clopidogrel. The decision for concurrent use of statins, angiotensin-converting enzyme inhibitors and beta-blockers (BB) was made according to recommendations in the guidelines. After the coronary intervention, transthoracic echocardiography assessments were performed at the coronary ICU using (iE33, Philips Medical System, Andover, MA) with a 3.5 MHz transducer.

Diagnosis of contrast-induced nephropathy

CIN is defined as an impairment of renal function and was measured as either a 25% increase in serum creatinine from baseline or a 0.5 mg/dL increase in absolute value when there was no alternative etiology within 72 hours after the first procedure.3

Diagnosis of ST-elevation myocardial infarction

Diagnoses were recorded by the participating physicians based on clinical, electrocardiographic and biochemical (elevated troponin levels) criteria. The type of myocardial infarction (ST-elevation vs. non-ST-elevation) and unstable angina were homogeneously defined and all patients were treated according to the currently available guidelines. p-PCI was performed in all patients.14

Risk scoring of contrast-induced nephropathy

Several clinical and laboratory variables are used to define the development of CIN. Recently, Mehran et al.,3 reported a simple risk score (Mehran risk score) for CIN after PCI. We calculated Mehran risk scores and compared them with oxidative stress parameters and other study variables to predict CIN in the present study.

Blood sampling and analyses

Blood samples were taken after at least 12 hours of fasting. Venous blood samples were obtained upon patient admission, drawn from a large ante-cubital vein without interruption of venous flow, using a 19-gauge butterfly needle connected to a plastic syringe. The contents of the syringe was transferred immediately to polypropylene tubes. These tubes were then centrifuged at 4000 rpm for min at 10–18°C. Supernatant plasma samples were stored in plastic tubes at -80°C until analysis. Glomerular filtration ratio was calculated using the Cockcroft-Gault Equation.15

Total antioxidant status, total oxidant status, and oxidative stress index analyses

Total antioxidative capacity levels were determined spectrophotometrically (Rel Assay Diagnostics, Gaziantep, Turkey). The method is based on the bleaching of the characteristic color of a more stable (2,2′-azino-bis[3-ethylbenzothiazoline-6-sulfonic acid]) radical cation by antioxidants.16 The assay has excellent precision and a coefficient of variation less than 3%. The results were expressed as mmol Trolox (Rel Assay) equivalent/L. Total oxidative status levels were measured spectrophotometrically (Relassay, Diagnostics, Gaziantep, Turkey). In this method, oxidants present in the sample oxidized the ferrous ion-o-dianisidine complex to ferric ion. The oxidation reaction was enhanced by glycerol molecules abundantly present in the reaction medium. The ferric ion produced a colored complex with xylenol orange in an acidic medium. The color intensity, which could be measured spectrophotometrically, was related to the total amount of oxidant molecules present in the sample.17 The assay was calibrated with hydrogen peroxide and the results were expressed in terms of micromolar hydrogen peroxide equivalent per liter (μmol H2O2 equivalent/L). The coefficient of variation for individual plasma samples was less than 3%. The levels of TAC and TOS were assayed in an Olympus AU 2700 autoanalyzer (Japan). The oxidative stress index (OSI) is defined as the ratio of TOS to TAC levels, expressed as a percentage. For the calculation of OSI, TAC units were represented as mmol/L, and the OSI value calculated according to the following formula: OSI (arbitrary unit)=TOS (mmol H2O2 equiv./L)/TAC (mmol Trolox equiv./L). Serum hs-CRP level was measured by a chemiluminescent immunometric assay within 12–24 h of admission using available commercial kits according to the manufacturer's instructions (Immulite 2000, Siemens Medical Solutions Diagnostics, NJ, US). The intra- and inter-assay coefficients of variation for hs-CRP were <8.7%.

Statistical analysis

SPSS version 16.0 software package was used for statistical analyses in this study. Categorical variables were expressed as frequency (%) and compared using the Chi-squared test. Kolmogorov-Smirnov test was used to test the distribution of numeric variables; those with normal distribution were expressed as mean ± standard deviation and were compared with Student's t-test. Data without normal distribution were expressed as median (inter-quartile range of 25%-75% percentiles) and were compared with the Mann-Whitney U test. In all statistical analyses, p value <0.05 was statistically significant. Univariate analysis and backward conditional binary logistic regression were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the prediction of CIN. Receiver operating characteristics (ROC) curve analysis was used to analyze the prognostic value of TAC, TOS and OSI for CIN, following STEMI. C-Statistic (area under the curve) was presented as a unified estimate of sensitivity and specificity according to the cut-off value that was obtained by a ROC curve analysis. The optimal cut-off value was defined as the value yielding the maximal Youden index, or the best combined sensitivity and specificity.18 C-Statistic (area under the curve) was presented as a unified estimate of sensitivity and specificity.

Results

A total of 300 patients (mean age: 62±13 years; range, 23–91 years) were included in this study. During the follow-up period, 50 patients (16.7%) developed CIN. Demographic and clinical characteristics of the patients with and without CIN are listed in Table 1. The patients with CIN were significantly older, predominantly female and with a higher incidence of hypertension when compared to the patients without CIN (p=0.01, p=0.01 and p<0.001, respectively). The incidence of diabetes, obesity and hyperlipidemia were similar between patients with and without CIN (for all parameters p>0.05). There were no statistically significant differences in cholesterol parameters (p>0.05) between patients with and without CIN. Left ventricle ejection fraction (LVEF) was significantly lower in patients with CIN compared to patients without CIN (p<0.001). Initial creatinine levels were significantly higher in patients with CIN compared to patients without CIN.

Table 1.

Demographic and clinical characteristics of patients with and without contrast-induced nephropathy.

  CIN (-) (n=250)  CIN (+) (n=50)  p value 
Female gender n (%)  39 (15.6)  18 (36.0)  0.001 
Diabetes n (%)  60 (24)  15 (30)  0.234 
Hypertension n (%)  95 (38)  33 (66)  <0.001 
Hyperlipidemia n (%)  60 (24)  11 (22)  0.460 
Obesity n (%)  90 (36.0)  19 (38.0)  0.453 
Age (years)  61.2±12.3  66.3±14.2  0.01 
Female gender  39 (15.6)  18 (36.0)  0.01 
Previous treatment
RAS blockers n (%)  45 (18.0)  8 (16.0)  0.458 
B Blockers n (%)  37 (14.8)  8 (16.0)  0.486 
Statins n (%)  31 (12.4)  5 (10.0)  0.421 
In-hospital treatment
RAS blockers n (%)  246 (98.4)  45 (90.0)  0.008 
B Blockers n (%)  234 (93.6)  41 (82.0)  0.012 
Statins n (%)  238 (95.2)  45 (90.0)  0.133 
Discharge treatment
RAS blockers n (%)  243 (97)  45 (90)  0.03 
B Blockers n (%)  234 (93.6)  41 (82)  0.012 
Statins n (%)  238 (95.2)  45 (90)  0.133 
Acetyl salicylic acid n (%)  245 (98)  49 (98)  0.66 
Clopidogrel/ticagrelor/prasugrel n (%)  243 (97)  49 (98)  0.65 
Opaque amount (cc)  72.5±9.3  78.3±17.4  0.001 
Opaque/CrCl ratio  1.0±0.4  1.5±1.0  <0.001 
Mehran Risk Score  3.0±3.5  6.9±6.2  <0.001 
Infarct-related artery0.963 
LAD  103 (45.6)  17 (47.2)   
Cx  36 (15.9)  6 (16.7)   
RCA  87 (38.5)  13 (36.1)   
Duration of CCU stay  2.0±0.5  2.6±1.2  <0.001 
LV ejection fraction  45.4±9.2  39.7±10.4  <0.001 
Sodium (mg/dl)  137.9±7.4  138.0±3.7  0.906 
Potassium (mg/dl)  4.3±0.5  4.5±0.6  0.019 
LDL (mg/dl)  108.5±35.5  105.0±35.5  0.526 
HDL (mg/dl)  41.0±9.4  40.4±7.1  0.648 
Triglyceride (mg/dl)  144.8±118.9  135.3±79.2  0.590 
Total cholesterol (mg/dl)  177.5±42.2  173.1±43.8  0.506 
Initial creatinine  1.0±0.2  1.2±0.3  <0.001 
Initial glucose  160.5±77.1  220.0±121.8  <0.001 
Hemoglobin  14.3±1.8  14.0±3.5  0.347 
Platelet count  238±71  227±86  0.361 
Initial CK-MB  50.4±58.6  52.0±56.3  0.865 
Initial troponin  0.4±0.9  0.6±0.9  0.160 
Peak CK-MB  201.4±153  252.3±186.5  0.042 
Peak Troponin  5.3±7.6  5.8±4.9  0.660 

Data presented as mean ± SD or number (%) of the patients.

CCU: coronary care unit; CIN: contrast-induced nephropathy; CK-MB: creatine kinase myocardial bundle; CrCl: creatinine clearance; Cx: circumflex; HDL: high density lipoprotein; LAD: left anterior descending artery; LDL: low density lipoprotein; LV: left ventricle; RAS: renin angiotensin system; RCA: right common artery.

There were no statistically significant differences in previous treatments including renin-angiotensin system (RAS) blockers, acetyl salicylic acid, clopidogrel or statins between patients with and without CIN (for all parameters p>0.05). Among in-hospital treatments, the use of BB and RAS blockers was lower in patients with CIN but use of other medications was similar among patients with and without CIN. Patients with CIN spent longer in the coronary care unit than patients without CIN (2.6±1.2 vs. 2.0±0.5 days; p<0.001). There were no statistically significant differences in the initial and peak cardiac enzymes including troponin and creatine kinase myocardial bundle between patients with and without CIN (for all parameters p>0.05). The mean Mehran risk score (6.9±6.2 vs. 3.0±3.5, p<0.001), contrast media volume (78.3±17.4 cc vs. 72.5±9.3 cc, p<0.001) and contrast media volume/glomerular filtration ratio (eGFR) (1.5±1.0 versus 1.0±0.4; p<0.001) were significantly higher in patients with CIN compared to patients without CIN.

Oxidative status and inflammation parameters are presented in Table 2. In patients with CIN, plasma TOS and OSI values were significantly higher (33.0±5.5 mmol H2O2 equiv./L vs. 27.7±5.0 mmol H2O2 equiv./L, p<0.001 and 28.9±6.8 vs. 19.2±4.5, p<0.001, respectively) and plasma TAC levels were significantly lower compared to those without CIN (1.1±0.2 mmol Trolox equiv./L vs. 1.4±0.2 mmol Trolox equiv./L p<0.001). Hs-CRP, UA and GGT levels were significantly higher in patients with CIN compared to patients without CIN (49.7±35.8 mg/L vs. 22.5±26.0 mg/L, p<0.001; 7.1±1.9 mg/dl vs. 6.0±1.2 mg/dl, p<0.001 and 43.8±48.09 U/L vs. 31.8±23.2 U/L, p=0.01; respectively)

Table 2.

Comparison of plasma oxidative stress and inflammation parameters in patients with and without contrast-induced nephropathy.

  CIN (-) (n=250)  CIN (+) (n=50)  p value 
hs-CRP (mg/L)  22.5±26.0  49.7±35.8  <0.001 
Uric acid (mg/dl)  6.0±1.2  7.1±1.9  <0.001 
TAS (mmol/Trolox Equiv./L)  1.4±0.2  1.1±0.2  <0.001 
TOS (lmol H2O2 Eq/L)  27.7±5.0  33.0±5.5  <0.001 
OSI  19.2±4.5  28.9±6.8  <0.001 
GGT  31.8±23.2  43.8± 48.09  0.01 

Data presented as mean ± SD.

OSI: oxidative stress index; Hs-CRP: high-sensitivity C-reactive protein; TAS: total antioxidative status; TOS: total oxidative status.

Prediction of contrast-induced nephropathy

Univariate analyses showed that TOS, TAC, OSI, LVEF, age, contrast media volume, contrast media volume/eGFR ratio, female gender, hypertension, initial glucose level, initial creatine level, Mehran score, UA level, hs-CRP level and GGT level were significantly associated with a higher risk of development of CIN (Table 3).

Table 3.

Univariate and multivariate regression analyses of predictors of contrast-induced nephropathy in the study population.

  Unadjusted odds ratio  CI  p value  Adjusted odds ratio  Confidence interval  p value 
TOS  1.18  1.11-1.25  <0.001       
TAS  0.009  0.002-0.043  <0.001       
OSI  1.35  1.24-1.45  <0.001  1.39  1.25-1.56  <0.001 
Age  1.03  1.00-1.05  0.01       
Gender (female)  3.04  1.55-5.95  0.001       
Hypertension  3.16  1.67-5.99  <0.001       
Initial creatinine  9.79  3.40-28.1  <0.001       
Initial glucose level  1.00  1.003-1.009  <0.001  1.006  1.00-1.01  0.02 
LV ejection fraction  0.93  0.90-0.97  <0.001       
Opaque amount/GFR ratio  2.8  1.7-4.4  <0.001  5.88  1.4-23.08  0.011 
Contrast media volume  1.04  1.01-1.06  0.002       
Mehran score  1.19  1.11-1.27  <0.001       
Uric acid  1.66  1.32-2.07  <0.001  1.36  0.94-1.96  0.09 
GGT  1.01  1.00-1.01  0.03       
Hs-CRP  1.02  1.01-1.03  <0.001  1.023  1.00-1.04  0.009 

CI: confidence interval; GFR: glomerular filtration rate; GGT: gamma-glutamyltransferase; Hs-CRP: high-sensitivity C-reactive protein; LV: left ventricle; OSI: oxidative stress index; TAS: total anti-oxidative status; TOS: total oxidative status.

A multivariate binary logistic regression analysis was carried out by including all the parameters that were associated with the development of CIN in the univariate analysis. This analysis showed that OSI (OR: 1.39; CI 95: 1.25-1.56, p<0.001), initial glucose level (OR: 1.006; CI 95%: 1.00-1.01, p=0.02), hs-CRP (OR: 1.023; CI 95: 1.00-1.04, p=0.009), contrast media volume/eGFR ratio (OR: 5:88; CI 95%: 1.4-23.08, p=0.011), and UA level (OR: 1.36; CI 95%: 0.94-1.96, p=0.09) remained as independent factors for CIN development (Table 3). ROC curve analysis showed that OSI (C-statistic: 0.81; CI 95%: 0.76-0.86, p<0.001), TAC (C-statistic: 0.80; CI 95%: 0.75-0.85, p<0.001) and TOS (C-statistic: 0.76; CI 95%: 0.68-0.83, p<0.001) were significant predictors of CIN following STEMI (Table 4, Figure 1). We calculated that a cut-off point of 30.5 for TOS, 1.2 for TAC and 26 for OSI could estimate the presence of CIN with a sensitivity of 72%, 76% and 74%, a specificity of 77%, 81% and 94%, respectively (Table 4).

Table 4.

Receiver operating characteristics curve analysis of oxidative parameters.

  C-statistic  95% CI  p value  Cut-off value  Sensitivity  Specificity 
TOS  0.760  0.68-0.83  <0.001  >30.5  72  77 
TAS  0.808  0.75-0.85  <0.001  ≤1.2  76  81 
OSI  0.816  0.765-0.860  <0.001  >26  74  94 

CI: confidence interval; OSI: oxidative status index; TAS: total anti-oxidative status; TOS: total oxidative status.

Figure 1.

Receiver operating characteristics curve with calculated area under the curve and optimal cut-off point for oxidative stress index, total antioxidant capacity, and total oxidant status to identify the presence of contrast-induced nephropathy. OSI: oxidative stress index; TAS: total antioxidant status; TOS: total oxidant status.

(0,07MB).

In correlation analysis, Mehran score correlated positively with OSI, hs-CRP, UA, contrast media volume/eGFR ratio levels and negatively correlated with TAC levels, while hs-CRP levels correlated positively with UA, GGT, OSI and TOS (Table 5).

Table 5.

Correlation analysis of study variables.

  hs-CRPUric acidGGTOSITACTOSContrast media volume/eGFR ratio
 
MEHRAN score  0.297  <0.001  0.158  0.009  0.00  ns  0.175  0.002  -0.127  0.028  0.092  ns  0.516  <0.001 
Hs-CRP (mg/L)      0.210  0.001  0.296  <0.001  0.168  0.006  -0.085  ns  0.162  0.009  0.109  0.07 
Uric Acid(mg/dl)          0.244  <0.001  0.165  0.006  -0.166  0.006  0.060  ns  0.105  ns 
GGT (U/L)              0.072  ns  -0.023  ns  0.107  ns  -0.110  ns 
OSI                  -0.737  <0.001  0.692  <0.001  0.092  ns 
TAC (mmol/Trolox Equiv./L)                      -0.063  ns  -0.097  ns 
TOS (lmol H2O2 Eq/L)                          0.000  ns 

GGT: Gamma-glutamyltransferase; OSI: oxidative stress index; Hs-CRP: high-sensitivity C-reactive protein; ns: not statistically significant; TAC: total antioxidative capacity; TOS: total oxidative status.

Discussion

The main findings of this study suggest that oxidative stress and inflammation parameters are associated with the development of CIN in patients presenting with acute STEMI. Oxidative stress is caused by increased ROS production and is associated with poor outcomes in cardiovascular diseases such as coronary artery disease (CAD) and CIN.4,9,19–22

Borekci et al.,20 demonstrated that OSI, UA and neutrophil to lymphocyte ratio were associated with spontaneous reperfusion in patients with STEMI. Similarly, Turan et al.21 reported that plasma TOS and OSI were significant factors associated with CAD complexity and severity in patients with acute coronary syndrome. Korkmaz et al.22 showed that thiol/disulfide homeostasis, a new oxidative marker, could be a good biochemical risk marker for CIN in STEMI patients who underwent p-PCI. Additionally, we have reported a positive association between atrial fibrillation development after STEMI and TAC, TOS and OSI.9 In these studies, the relationship between CIN and oxidative stress markers in patients with STEMI was not determined. Data from the current study suggest that plasma TAC, TOS and OSI were increased in patients with CIN when compared to those without CIN in a STEMI patient population. Thus, increased oxidative stress may contribute to pathogenesis in these patients.

CIN is a serious complication of p-PCI after STEMI and is associated with poor clinical outcomes such as prolonged hospital stays, rising costs, and increased short- and long-term morbidity and mortality.2,23 It is, therefore, important to estimate which patients may develop CIN. There are several established parameters for predicting CIN development. Yildiz et al.24 showed that serum osmolality is a predictive factor for CIN development, while Gohbara et al.25 determined that acidosis was associated with CIN development in patients with STEMI. Our results showed that OSI, initial glucose levels, contrast media volume/eGFR ratio, UA and hs-CRP levels were associated with CIN development in patients with STEMI after p-PCI. Previous studies have also shown similar results.26–28 Contrast volume and basal renal insufficiency are important risk factors for CIN29; accordingly, the contrast media volume/eGFR ratio is a good indicator for CIN.28 Our study also indicated that contrast media volume/eGFR ratio was a powerful predictor of CIN development.

There is a demonstrated association between inflammation and CIN in the literature.28,30–33 Liu et al.32 showed that an increase in hs-CRP was a significant and independent predictor of CIN in patients with STEMI after p-PCI. Oweis et al.34 showed that interleukin-33 levels were elevated in patients with CIN. Gu et al.33 reported that an elevation of the inflammatory biomarkers hs-CRP and procalcitonin was a risk factor for postoperative CIN. Similarly, in the present study, hs-CRP levels were significantly higher in patients with CIN compared to patients without CIN. This indicates that higher hs-CRP may be associated with the development of CIN in patients presenting with STEMI.

Although several studies have shown that pharmacological agents such as theophylline, fenoldopam, mannitol, iloprost, furosemide, dopamine, hemofiltration, ascorbic acid, NAC and sodium bicarbonate (NaHCO3) could prevent the development of CIN, it is still unclear which are the best agents for the prevention of CIN.35 Among these agents, the use of NAC and NaHCO3 with physiological saline was recommended as a good strategy to prevent CIN.35 Additionally, statins that have pleiotropic effects such as a decrease in free oxygen radicals, increase in nitrous oxide production and increment of vascular smooth muscle relaxation, can also prevent CIN.36 The present study supported the beneficial effects of the above mentioned agents. In future studies, there is a need to focus on agents and foods with antioxidant effects; individuals should also be advised to increase the amount of antioxidants in their diets.

In this study we have demonstrated lower antioxidant capacity and higher oxidative and inflammatory status in STEMI patients. During the acute phase of STEMI, the oxidative and inflammatory response may influence the patient's baseline cardio-renal reserves. The addition of oxidative and inflammatory parameters to the current risk models derived from clinical, angiographic, and laboratory-based variables and to the previously validated Mehran risk score13 may result in significant improvement in the prediction of CIN.

Our study has several limitations: the study population consisted of patients treated with different modes of STEMI and the number of CIN patients was too small for definitive conclusions. Additional oxidative stress parameters such as serum prolidase activity, malondialdehyde, superoxide dismutase etc., were not examined, and markers for the detection of renal failure, such as NGAL, cystatin C, urinary Kim-1 were also not analyzed.

Conclusions

The present study suggests that in a patient population with STEMI, oxidative stress and inflammation were significantly higher in patients with CIN when compared to patients without CIN. Further studies are needed to establish the pathophysiological and clinical significance of increased oxidative stress and inflammation, and to investigate the effect of antioxidant and anti-inflammatory agents in patients with AMI.

Conflicts of interest

The authors have no conflicts of interest to declare.

References
[1]
F.-J. Neumann, M. Sousa-Uva, A. Ahlsson, et al.
ESC/EACTS Guidelines on myocardial revascularization.
Eur Heart J, 2018 (2018), pp. ehy394
[2]
R. Gupta, H.S. Gurm, D.L. Bhatt, et al.
Renal failure after percutaneous coronary intervention is associated with high mortality.
Catheteriz Cardiovasc Interv, 64 (2005), pp. 442-448
[3]
R. Mehran, E.D. Aymong, E. Nikolsky, et al.
A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.
J Am Coll Cardiol, 44 (2004), pp. 1393-1399
[4]
A. Pisani, E. Riccio, M. Andreucci, et al.
Role of reactive oxygen species in pathogenesis of radiocontrast-induced nephropathy.
BioMed Res Int, (2013), pp. 2013
[5]
E. Seeliger, M. Sendeski, C.S. Rihal, et al.
Contrast-induced kidney injury: mechanisms, risk factors, and prevention.
Eur Heart J, 33 (2012), pp. 2007-2015
[6]
C. Mamoulakis, K. Tsarouhas, I. Fragkiadoulaki, et al.
Contrast-induced nephropathy: basic concepts, pathophysiological implications and prevention strategies.
Pharmacol Therapeut, 180 (2017), pp. 99-112
[7]
C. Sandhu, A.-M. Belli, D.B. Oliveira.
The role of N-acetylcysteine in the prevention of contrast-induced nephrotoxicity.
Cardiovasc Interv Radiol, 29 (2006), pp. 344-347
[8]
N. Pannu, N. Wiebe, M. Tonelli, et al.
Prophylaxis strategies for contrast-induced nephropathy.
JAMA, 295 (2006), pp. 2765-2779
[9]
H.A. Bas, F. Aksoy, A. Icli, et al.
The association of plasma oxidative status and inflammation with the development of atrial fibrillation in patients presenting with ST elevation myocardial infarction.
Scand J Clin Lab Invest, 77 (2017), pp. 77-82
[10]
A. Ninić, M. Sopić, J. Munjas, et al.
Association between superoxide dismutase isoenzyme gene expression and total antioxidant status in patients with an end-stage renal disease.
Balkan Med J, 35 (2018), pp. 431
[11]
A. Gönenç, A. Hacışevki, Y. Tavil, et al.
Oxidative stress in patients with essential hypertension: a comparison of dippers and non-dippers.
Eur J Int Med, 24 (2013), pp. 139-144
[12]
O. Shemesh, H. Golbetz, J.P. Kriss, et al.
Limitations of creatinine as a filtration marker in glomerulopathic patients.
Kidney Int, 28 (1985), pp. 830-838
[13]
R. Mehran, E. Nikolsky.
Contrast-induced nephropathy: definition, epidemiology, and patients at risk.
Kidney Int, 69 (2006), pp. S11-S15
[14]
K. Thygesen, J.S. Alpert, A.S. Jaffe, et al.
Third universal definition of myocardial infarction.
Eur Heart J, 33 (2012), pp. 2551-2567
[15]
D.W. Cockcroft, H. Gault.
Prediction of creatinine clearance from serum creatinine.
Nephron, 16 (1976), pp. 31-41
[16]
O. Erel.
A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation.
Clin Biochem, 37 (2004), pp. 277-285
[17]
O. Erel.
A new automated colorimetric method for measuring total oxidant status.
Clin Biochem, 38 (2005), pp. 1103-1111
[18]
W.J. Youden.
Index for rating diagnostic tests.
[19]
F.J. Kelly, J.C. Fussell.
Role of oxidative stress in cardiovascular disease outcomes following exposure to ambient air pollution.
Free Rad Biol Med, 110 (2017), pp. 345-367
[20]
A. Börekçi, M. Gür, C. Türkoğlu, et al.
Oxidative stress and spontaneous reperfusion of infarct-related artery in patients with ST-segment elevation myocardial infarction.
Clin Appl Thromb/Hemost, 22 (2016), pp. 171-177
[21]
T. Turan, Ü. Menteşe, M.T. Ağaç, et al.
The relation between intensity and complexity of coronary artery lesion and oxidative stress in patients with acute coronary syndrome.
Anatol J Cardiol, 15 (2015), pp. 795
[22]
A. Korkmaz, B. Ozyazgan, A. Kosem, et al.
The role of thiol levels in predicting contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.
Northern Clin Istanbul, 6 (2019), pp. 210
[23]
P. Liss, P. Persson, P. Hansell, et al.
Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media.
Kidney Int, 70 (2006), pp. 1811-1817
[24]
I. Yildiz, P.O. Yildiz, I. Rencuzogullari, et al.
Association of serum osmolarity with contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction.
Angiology, (2019),
[25]
M. Gohbara, A. Hayakawa, Y. Akazawa, et al.
Association between acidosis soon after reperfusion and contrast-induced nephropathy in patients with a first-time ST-segment elevation myocardial infarction.
J Am Heart Assoc, 6 (2017), pp. e800063
[26]
T. Çınar, V.O. Tanık, E. Aruğaslan, et al.
The association of PRECISE-DAPT score with development of contrast-induced nephropathy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
Cardiovasc Interv Therapeut, (2018), pp. 1-9
[27]
A. Kurtul, M. Yarlioglues, M. Duran.
Predictive value of CHA2DS2-VASC score for contrast-induced nephropathy after percutaneous coronary intervention for acute coronary syndrome.
Am J Cardiol, 119 (2017), pp. 819-825
[28]
T. Nozue, I. Michishita, T. Iwaki, et al.
Contrast medium volume to estimated glomerular filtration rate ratio as a predictor of contrast-induced nephropathy developing after elective percutaneous coronary intervention.
J Cardiol, 54 (2009), pp. 214-220
[29]
P.B. Persson, P. Hansell, P. Liss.
Pathophysiology of contrast medium-induced nephropathy.
[30]
P.C.Y. Wong, Z. Li, J. Guo, et al.
Pathophysiology of contrast-induced nephropathy.
Int J Cardiol, 158 (2012), pp. 186-192
[31]
G. Qian, Y. Zhou, H.-B. Liu, et al.
Clinical profile and long-term prognostic factors of a young Chinese Han population (≤40 years) having ST-segment elevation myocardial infarction.
Acta Cardiol Sinica, 31 (2015), pp. 390
[32]
Y. Liu, N. Tan, Y.-L. Zhou, et al.
High-sensitivity C-reactive protein predicts contrast-induced nephropathy after primary percutaneous coronary intervention.
J Nephrol, 25 (2012), pp. 332-340
[33]
G. Gu, X. Yuan, Y. Zhou, et al.
Elevated high-sensitivity C-reactive protein combined with procalcitonin predicts high risk of contrast-induced nephropathy after percutaneous coronary intervention.
BMC Cardiovasc Disord, 19 (2019), pp. 152
[34]
A.O. Oweis, S.A. Alshelleh, A.K. Daoud, et al.
Inflammatory milieu in contrast-induced nephropathy: a prospective single-center study.
Int J Nephrol Renovasc Dis, 11 (2018), pp. 211
[35]
D. Patschan, I. Buschmann, O. Ritter.
Contrast-induced nephropathy: update on the use of crystalloids and pharmacological measures.
Int J Nephrol, 2018 (2018),
[36]
E. Ongini, F. Impagnatiello, A. Bonazzi, et al.
Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties.
Proc Natl Acad Sci U S A, 101 (2004), pp. 8497-8502
Copyright © 2020. Sociedade Portuguesa de Cardiologia
Idiomas
Revista Portuguesa de Cardiologia

Receba a nossa Newsletter

Opções de artigo
Ferramentas
en pt

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.