Clinical Investigations Impact of Metabolic Syndrome on Development of Contrast-Induced Nephropathy After Elective Percutaneous Coronary Intervention Among Nondiabetic Patients
Address for correspondence: Ozgur Ulas Ozcan, MD, Cardiology Department, Ankara University, School of Medicine, Ovecler 1042nd Street 45/14, 06460 Cankaya-Ankara, Turkey, [email protected]
Ozgur Ulas Ozcan, MD; Hacer Adanir Er, MD; Sadi Gulec, MD; Elif Ezgi Ustun, MD; Demet Menekse Gerede, MD; Huseyin Goksuluk, MD; Cansin Tulunay Kaya, MD; Cetin Erol, MD Cardiology Department, Ankara University, Ankara, Turkey
Background: Identifying patients who are vulnerable to development of contrast-induced nephropathy (CIN) is essential because of its association with prolonged hospitalization, increased cost, and increased in-hospital and long-term mortality rates. Hypothesis: Individual components of metabolic syndrome (MetS) are well-established risk factors for kidney injury. Nondiabetic patients diagnosed with MetS might be at an increased risk of developing CIN after elective percutaneous coronary intervention (PCI). Methods: A total of 599 nondiabetic patients were enrolled, of whom 313 met the MetS criteria and 286 were included in the control group. Patients were evaluated for development of CIN after elective PCI. Results: Contrast-induced nephropathy occurred in 9.3% (29 of 313) of the MetS group and 4.9% (14 of 286) of the control group (P = 0.04). The multivariable regression model revealed that baseline glomerular filtration rate < 30 mL/min, multivessel intervention, and MetS increased and use of statin decreased the probability of CIN independent from confounding factors (odds ratio [OR]: 7.84, 95% confidence interval [CI]: 3.46-24.36, P < 0.01 for baseline glomerular filtration rate < 30 mL/min; OR: 0.82, 95% CI: 0.42-0.96, P = 0.02 for statin use; OR: 2.64, 95% CI: 1.46-6.56, P < 0.01 for multivessel intervention; and OR: 1.66, 95% CI: 1.12-2.61, P = 0.03 for MetS). Conclusions: Metabolic syndrome is a risk factor for CIN in patients with stable coronary artery disease who undergo elective PCI. We suggest that clinicians recognize the patients with MetS before elective coronary interventions.
Introduction Contrast-induced nephropathy (CIN) causes 10% of hospitalacquired renal failure.1,2 Contrast-induced nephropathy is diagnosed as an absolute ≥0.5 mg/dL or a relative ≥25% increase in serum creatinine (SCr) above the baseline within 24 to 72 hours of administration of intravascular contrast media with no other explainable cause of renal injury.3,4 The reported incidence of CIN varies widely across the literature (2%–50%) due to different diagnostic criteria used and various risk profiles of the population studied.4,5 Identifying patients who are vulnerable to development of CIN is essential because of its association with prolonged hospitalization, increased cost, and increased in-hospital and long-term mortality rates.5,6 The metabolic syndrome (MetS) is a combination of risk factors including hypertension, insulin resistance, central The authors have no funding, financial relationships, or conflicts of interest to disclose
150
Clin. Cardiol. 38, 3, 150–156 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22364 © 2015 Wiley Periodicals, Inc.
obesity, impaired glucose tolerance, and dyslipidemia, which are highly associated with increased mortality and morbidity of cardiovascular diseases.7 Metabolic syndrome predicts reduced renal function and chronic kidney disease.8 The components of MetS, such as abdominal obesity, insulin resistance, dyslipidemia, and hypertension, have been shown to contribute the development of renal injury.8 – 10 On the basis of these data, we hypothesized that patients diagnosed with MetS might be at an increased risk of developing CIN. Therefore, we designed a prospective cohort study to investigate the impact of MetS on the development of CIN in nondiabetic patients who underwent nonurgent percutaneous coronary intervention (PCI).
Methods An observational prospective cohort study was designed to determine whether MetS predicts the development of CIN after elective PCI. All patients scheduled for elective PCI were screened for eligibility from February 2014 until July Received: September 11, 2014 Accepted with revision: October 26, 2014
Figure 1. Flow diagram of patients. The diagram includes detailed information on the excluded patients. Abbreviations: CIN, contrast-induced nephropathy; MetS, metabolic syndrome.
2014. Metabolic syndrome was defined, according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III), as the presence of ≥3 of these components: high fasting glucose (fasting serum glucose ≥100 mg/dL), abdominal obesity (given as waist circumference >102 cm in men and >88 cm in women), high blood pressure (≥130/≥85 mm Hg or drug treatment for hypertension), hypertriglyceridemia (serum triglycerides ≥150 mg/dL), low high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL in men and < 50 mg/dL in women).3 Exclusion criteria included diabetes mellitus (DM), acute coronary events, low left ventricular ejection fraction, known acute renal failure, end-stage renal failure requiring hemodialysis, contrast allergy, exposure to nephrotoxic agents (nonsteroidal anti-inflammatory drugs, aminoglycosides, tacrolimus, amphotericin B, cisplatin, and cyclosporine) within 1 week before PCI, and exposure to contrast agents within 1 week before the procedure. Acute renal failure was identified as an increase in SCr by ≥1.5× baseline, which is known to or presumed to have occurred within the prior 7 days. A total of 599 nondiabetic patients were enrolled, of whom 313 met the MetS criteria and 286 were included in the control group (Figure 1). All patients provided written informed consent. This study complied with the Declaration of Helsinki and was approved by the institutional committee on human research and registered at ClinicalTrials.gov (identifier NCT02192372). Blood samples were collected to measure serum levels of creatinine, glucose, hemoglobin, and lipids following
a fasting period of 8 hours. Serum creatinine levels were measured at 24 and 48 hours after the procedure. Contrast-induced nephropathy was defined as an increase in SCr of ≥25% or ≥0.5 mg/dL above the baseline value 24 or 48 hours after angiography. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula: (140 − age) × weight (kg) / SCr (mg/dL) × 72 (×0.85 for females). The coronary angiography was performed using isoosmolar, nonionic contrast medium (iodixanol, Visipaque 320; Opakim, Turkey). All of the recruited patients had ≥1 coronary intervention. Total volume of the contrast agent used during the procedure was recorded for each patient. All patients received standard protocol of hydration with 100 mL/h of saline for 12 hours before and after the procedure. No other medication was administered routinely unless CIN was seen. Sample size was calculated with assumed event rates 14% and 3.6%, respectively, in MetS patients and the control group, which is in agreement with a previous prospective study.11 The total sample size of 380 was necessary for a 2-sided test with 0.95 statistical power and α level of 0.05. We recruited 313 patients with MetS and 286 ageand sex-adjusted controls. The endpoint of this trial was the development of CIN. All analyses were performed using SPSS software version 20 for Windows (IBM Corp., Armonk, NY). Data are expressed as frequencies for discrete variables and as mean ± SD for continuous variables. The Shapiro-Wilk test assessed distribution of data. Continuous variables were compared by the Student Clin. Cardiol. 38, 3, 150–156 (2015) O. Ozcan et al: CIN in metabolic syndrome Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22364 © 2015 Wiley Periodicals, Inc.
151
unpaired t test or Mann-Whitney U test according to the distribution of data. The χ2 analysis or Fisher exact test was used to assess the significance of differences between dichotomous variables. The following were assessed in univariate logistic regression analysis: age, sex, body mass index, presentation of hypertension and MetS, smoking status, history of myocardial infarction, presentation with chronic renal failure; plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, and triglycerides before the procedure; use of statins, β-blockers, ACEI/ARB, or calcium channel blockers; and presence of a multivessel intervention. Univariate correlates of periprocedural infarction with a P value < 0.1 were included in the multiple logistic regression analyses. Receiver operating characteristic curve analyses of baseline GFR for
the prediction of CIN and determination of the cutoff point for baseline GFR were performed. All tests were 2-sided, and the results with a P value < 0.05 were considered significant.
Results Seven hundred and seventy-four consecutive patients scheduled for elective PCI were screened. A total of 175 patients were excluded for various reasons (Figure 1). Therefore, this study included 599 patients who were allocated to MetS and control groups (Figure 1). Comparisons of different demographic, clinical, and angiographic characteristics are shown in Table 1. Most of the patients were male (70%), with a mean age of 61.5 years. Baseline characteristics were significantly different between patients with MetS and those without MetS. Compared with control subjects, patients in
Table 1. Baseline Demographics and Clinical and Angiographic Characteristics of Patients Patients With MetS (n = 313)
Patients Without MetS (n = 286)
P Value
61.6 ± 9.2
62.1 ± 10.2
0.38
Male sex
222 (71)
197 (69)
0.84
Hypertension
260 (83)
155 (54)
Address for correspondence: Ozgur Ulas Ozcan, MD, Cardiology Department, Ankara University, School of Medicine, Ovecler 1042nd Street 45/14, 06460 Cankaya-Ankara, Turkey, [email protected]
Ozgur Ulas Ozcan, MD; Hacer Adanir Er, MD; Sadi Gulec, MD; Elif Ezgi Ustun, MD; Demet Menekse Gerede, MD; Huseyin Goksuluk, MD; Cansin Tulunay Kaya, MD; Cetin Erol, MD Cardiology Department, Ankara University, Ankara, Turkey
Background: Identifying patients who are vulnerable to development of contrast-induced nephropathy (CIN) is essential because of its association with prolonged hospitalization, increased cost, and increased in-hospital and long-term mortality rates. Hypothesis: Individual components of metabolic syndrome (MetS) are well-established risk factors for kidney injury. Nondiabetic patients diagnosed with MetS might be at an increased risk of developing CIN after elective percutaneous coronary intervention (PCI). Methods: A total of 599 nondiabetic patients were enrolled, of whom 313 met the MetS criteria and 286 were included in the control group. Patients were evaluated for development of CIN after elective PCI. Results: Contrast-induced nephropathy occurred in 9.3% (29 of 313) of the MetS group and 4.9% (14 of 286) of the control group (P = 0.04). The multivariable regression model revealed that baseline glomerular filtration rate < 30 mL/min, multivessel intervention, and MetS increased and use of statin decreased the probability of CIN independent from confounding factors (odds ratio [OR]: 7.84, 95% confidence interval [CI]: 3.46-24.36, P < 0.01 for baseline glomerular filtration rate < 30 mL/min; OR: 0.82, 95% CI: 0.42-0.96, P = 0.02 for statin use; OR: 2.64, 95% CI: 1.46-6.56, P < 0.01 for multivessel intervention; and OR: 1.66, 95% CI: 1.12-2.61, P = 0.03 for MetS). Conclusions: Metabolic syndrome is a risk factor for CIN in patients with stable coronary artery disease who undergo elective PCI. We suggest that clinicians recognize the patients with MetS before elective coronary interventions.
Introduction Contrast-induced nephropathy (CIN) causes 10% of hospitalacquired renal failure.1,2 Contrast-induced nephropathy is diagnosed as an absolute ≥0.5 mg/dL or a relative ≥25% increase in serum creatinine (SCr) above the baseline within 24 to 72 hours of administration of intravascular contrast media with no other explainable cause of renal injury.3,4 The reported incidence of CIN varies widely across the literature (2%–50%) due to different diagnostic criteria used and various risk profiles of the population studied.4,5 Identifying patients who are vulnerable to development of CIN is essential because of its association with prolonged hospitalization, increased cost, and increased in-hospital and long-term mortality rates.5,6 The metabolic syndrome (MetS) is a combination of risk factors including hypertension, insulin resistance, central The authors have no funding, financial relationships, or conflicts of interest to disclose
150
Clin. Cardiol. 38, 3, 150–156 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22364 © 2015 Wiley Periodicals, Inc.
obesity, impaired glucose tolerance, and dyslipidemia, which are highly associated with increased mortality and morbidity of cardiovascular diseases.7 Metabolic syndrome predicts reduced renal function and chronic kidney disease.8 The components of MetS, such as abdominal obesity, insulin resistance, dyslipidemia, and hypertension, have been shown to contribute the development of renal injury.8 – 10 On the basis of these data, we hypothesized that patients diagnosed with MetS might be at an increased risk of developing CIN. Therefore, we designed a prospective cohort study to investigate the impact of MetS on the development of CIN in nondiabetic patients who underwent nonurgent percutaneous coronary intervention (PCI).
Methods An observational prospective cohort study was designed to determine whether MetS predicts the development of CIN after elective PCI. All patients scheduled for elective PCI were screened for eligibility from February 2014 until July Received: September 11, 2014 Accepted with revision: October 26, 2014
Figure 1. Flow diagram of patients. The diagram includes detailed information on the excluded patients. Abbreviations: CIN, contrast-induced nephropathy; MetS, metabolic syndrome.
2014. Metabolic syndrome was defined, according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III), as the presence of ≥3 of these components: high fasting glucose (fasting serum glucose ≥100 mg/dL), abdominal obesity (given as waist circumference >102 cm in men and >88 cm in women), high blood pressure (≥130/≥85 mm Hg or drug treatment for hypertension), hypertriglyceridemia (serum triglycerides ≥150 mg/dL), low high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL in men and < 50 mg/dL in women).3 Exclusion criteria included diabetes mellitus (DM), acute coronary events, low left ventricular ejection fraction, known acute renal failure, end-stage renal failure requiring hemodialysis, contrast allergy, exposure to nephrotoxic agents (nonsteroidal anti-inflammatory drugs, aminoglycosides, tacrolimus, amphotericin B, cisplatin, and cyclosporine) within 1 week before PCI, and exposure to contrast agents within 1 week before the procedure. Acute renal failure was identified as an increase in SCr by ≥1.5× baseline, which is known to or presumed to have occurred within the prior 7 days. A total of 599 nondiabetic patients were enrolled, of whom 313 met the MetS criteria and 286 were included in the control group (Figure 1). All patients provided written informed consent. This study complied with the Declaration of Helsinki and was approved by the institutional committee on human research and registered at ClinicalTrials.gov (identifier NCT02192372). Blood samples were collected to measure serum levels of creatinine, glucose, hemoglobin, and lipids following
a fasting period of 8 hours. Serum creatinine levels were measured at 24 and 48 hours after the procedure. Contrast-induced nephropathy was defined as an increase in SCr of ≥25% or ≥0.5 mg/dL above the baseline value 24 or 48 hours after angiography. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula: (140 − age) × weight (kg) / SCr (mg/dL) × 72 (×0.85 for females). The coronary angiography was performed using isoosmolar, nonionic contrast medium (iodixanol, Visipaque 320; Opakim, Turkey). All of the recruited patients had ≥1 coronary intervention. Total volume of the contrast agent used during the procedure was recorded for each patient. All patients received standard protocol of hydration with 100 mL/h of saline for 12 hours before and after the procedure. No other medication was administered routinely unless CIN was seen. Sample size was calculated with assumed event rates 14% and 3.6%, respectively, in MetS patients and the control group, which is in agreement with a previous prospective study.11 The total sample size of 380 was necessary for a 2-sided test with 0.95 statistical power and α level of 0.05. We recruited 313 patients with MetS and 286 ageand sex-adjusted controls. The endpoint of this trial was the development of CIN. All analyses were performed using SPSS software version 20 for Windows (IBM Corp., Armonk, NY). Data are expressed as frequencies for discrete variables and as mean ± SD for continuous variables. The Shapiro-Wilk test assessed distribution of data. Continuous variables were compared by the Student Clin. Cardiol. 38, 3, 150–156 (2015) O. Ozcan et al: CIN in metabolic syndrome Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22364 © 2015 Wiley Periodicals, Inc.
151
unpaired t test or Mann-Whitney U test according to the distribution of data. The χ2 analysis or Fisher exact test was used to assess the significance of differences between dichotomous variables. The following were assessed in univariate logistic regression analysis: age, sex, body mass index, presentation of hypertension and MetS, smoking status, history of myocardial infarction, presentation with chronic renal failure; plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, and triglycerides before the procedure; use of statins, β-blockers, ACEI/ARB, or calcium channel blockers; and presence of a multivessel intervention. Univariate correlates of periprocedural infarction with a P value < 0.1 were included in the multiple logistic regression analyses. Receiver operating characteristic curve analyses of baseline GFR for
the prediction of CIN and determination of the cutoff point for baseline GFR were performed. All tests were 2-sided, and the results with a P value < 0.05 were considered significant.
Results Seven hundred and seventy-four consecutive patients scheduled for elective PCI were screened. A total of 175 patients were excluded for various reasons (Figure 1). Therefore, this study included 599 patients who were allocated to MetS and control groups (Figure 1). Comparisons of different demographic, clinical, and angiographic characteristics are shown in Table 1. Most of the patients were male (70%), with a mean age of 61.5 years. Baseline characteristics were significantly different between patients with MetS and those without MetS. Compared with control subjects, patients in
Table 1. Baseline Demographics and Clinical and Angiographic Characteristics of Patients Patients With MetS (n = 313)
Patients Without MetS (n = 286)
P Value
61.6 ± 9.2
62.1 ± 10.2
0.38
Male sex
222 (71)
197 (69)
0.84
Hypertension
260 (83)
155 (54)
