Renal Function
Association of Glomerular Filtration Rate With Slow Coronary Flow in Patients With Normal to Mildly Impaired Renal Function
Angiology 2014, Vol. 65(9) 844-848 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714522106 ang.sagepub.com
Fatih Akin, MD1, Omer Celik, MD2, Burak Ayc¸a, MD3, Ahmet Arif Yalc¸ın, MD2, Ibrahim Altun, MD1, and Nuri Ko¨se, MD4
Abstract We evaluated the association between estimated glomerular filtration rate (eGFR) and slow coronary flow (SCF) in patients with normal to mildly impaired renal function; 211 patients with angiographically proven SCF and 219 controls were studied. Patients were categorized based on the angiographic findings as with or without SCF. We used the Modification of Diet in Renal Disease equation to calculate eGFR. The frequency of mildly decreased eGFR, serum uric acid levels, and eGFR was higher in the SCF group. Patients with mildly impaired renal function had higher thrombolysis in myocardial infarction frame counts in 3 major coronary arteries. In logistic regression analysis, uric acid (odds ratio [OR] ¼ 1.323, 95% confidence interval [CI] ¼ 1.109-1.572, P ¼ .002) and eGFR (OR ¼ 0.972, 95% CI ¼ 0.957-0.987, P < .001) were independent correlates of SCF. In conclusion, eGFR was significantly correlated with SCF in patients with normal to mildly impaired renal function. Keywords slow coronary flow, renal function, glomerular filtration rate, uric acid
Introduction
Study Population
Slow coronary flow (SCF) is an angiographic finding characterized by slow progression of contrast in the coronary arteries in the absence of obstructive coronary disease.1 The incidence of SCF ranges between 1% and 7% among patients who undergo coronary angiography.2,3 The underlying pathophysiological mechanisms and the clinical importance of SCF are not clearly defined. Some mechanisms that are possibly involved in the SCF include small-vessel dysfunction,4 diffuse atherosclerosis,5 inflammation,6 endothelial dysfunction,7 and increased platelet aggregability.8 Moreover, SCF is associated with increased cardiovascular (CV) mortality.9 Chronic kidney disease is recognized as a CV risk factor.10 Several studies suggest that mildly decreased estimated glomerular filtration rate (eGFR) is associated with increased rates of death from CV diseases.11,12 Yilmaz and Yalta13 have shown that impaired kidney function with the exclusion of those with severe renal dysfunction is associated with impaired thrombolysis in myocardial infarction (TIMI) flow. Another study showed that coronary TIMI flow is impaired in patients with end-stage renal disease (ESRD).14 However, there have been no studies investigating the association between mildly decreased eGFR and SCF. Therefore, we evaluated the association between mildly decreased eGFR and SCF.
Patients who underwent coronary angiography between March 2009 and August 2013 were evaluated for possible inclusion in the study. A total of 211 consecutive patients with SCF and 219 age- and gender-matched patients (control group) were included in the present study after the following exclusions: history of coronary artery disease (CAD) or sign of CAD on coronary angiograms, valvular heart disease, congestive heart failure, moderate and severely decreased eGFR based on the Modification of Diet in Renal Disease (MDRD) definition, concomitant inflammatory diseases, and neoplastic diseases. Patients taking uric acid-lowering agents were also excluded from the study. Detailed physical examination and an electrocardiogram were performed in all patients. The clinical risk 1
Department of Cardiology, Mug˘la Sitki Kocman University School of Medicine, Mugla, Turkey 2 Department of Cardiology, Mehmet Akif Ersoy Chest and Cardiovascular Surgery Education and Research Hospital, Istanbul, Turkey 3 Department of Cardiology, Bag˘cilar Education and Research Hospital, Istanbul, Turkey 4 Department of Cardiology, Mug˘la Yucelen Hospital, Mugla, Turkey Corresponding Author: Fatih Akin, Department of Cardiology, Mug˘la Sitki Kocman University School of Medicine, Mugla, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 10, 2015
Akin et al
845
factors for the patients, such as age, gender, hypertension (HT), diabetes mellitus (DM), history of hyperlipidemia, and smoking status, were noted. The local ethical committee approved the study protocol.
Definitions Hypertension was defined as a blood pressure 140/90 mm Hg or antihypertensive drug use. The DM was defined as fasting blood glucose 126 mg/dL on 2 occasions or being on treatment. Current smokers were defined as having a history of smoking within the past year. The assessment of renal function was based on the MDRD eGFR equation.15 According to the MDRD criteria, normal eGFR was defined as 90 mL/min/1.73 m2 and mildly decreased eGFR was defined as 60 to 89 mL/min/1.73 m2.
Evaluation of Coronary Blood Flow Coronary angiography was commonly indicated because of clinical symptoms or results of noninvasive tests that suggested myocardial ischemia. Coronary angiography was performed using the standard Judkins technique. During coronary angiography, an iopromide contrast medium (Ultravist 370; Schering AG, Berlin, Germany) was manually injected (6-10 mL of contrast agent at each standard views using right and left, and cranial and caudal angulations). Coronary flow rates of all patients were documented by the TIMI frame count (TFC) method, with cineangiography at 25 frames/sec. The TFC was determined for each major coronary vessel, by 2 trained cardiologists, according to the method first described by Gibson et al.16 Both investigators were blinded to the clinical details of the individual case. The TFCs of the left anterior descending (LAD) and circumflex (Cx) arteries were assessed in either the right anterior oblique projection with caudal angulations or the left anterior oblique projection with cranial angulations and that of right coronary artery (RCA) usually in straight left anterior oblique projection. Since the LAD coronary artery is usually longer than the RCA and the Cx, and the TFC for this vessel is often higher, the LAD frame counts were corrected by dividing by 1.7. Patients with a TFC of greater than 2 standard deviations from the normal published range16 for any 1 of the 3 vessels (40.6 frames for LAD, 29.8 frames for Cx, and 27.3 frames for RCA) were considered to have SCF.
Laboratory Measurements A fasting venous blood sample was obtained in the morning before coronary angiography. Levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in serum were measured using an Abbott Aeroset autoanalyzer with original kits (Abbott Laboratories, Abbott Park, Illinois). Low-density lipoprotein cholesterol (LDL-C) levels were calculated using the Friedewald equation. Serum uric acid (SUA) levels were measured using an enzymatic colorimetric test on a Roche/Hitachi analyzer (Roche/Hitachi Modular Analytics, Roche Diagnostics, GmBH, Mannheim, Germany). Hemoglobin and other hematologic parameters
Table 1. Baseline, Clinical, and Laboratory Characteristics of SCF and Normal Flow Groups.
Age, years Male gender, n (%) Hypertension, n (%) Diabetes, n (%) Smoking, n (%) Total cholesterol, mmol/L LDL cholesterol, mmol/L HDL cholesterol, mmol/L Triglyceride, mmol/L Uric acid, mg/dL Creatinine, mg/dL eGFR, mL/min/1.73 m2 Mildly decreased eGFR, n (%) Medications, n (%) Aspirin b-Blocker ACEI or ARB Statin Diuretic
Normal Flow Group n ¼ 219
SCF Group n ¼ 211
P
53.6 + 8.6 131 (59.8) 65 (29.6) 32 (14.6) 37 (16.8) 198 + 42 124 + 37 47 + 13 149 + 71 4.4 + 1.4 0.8 + 0.1 95.7 + 19 92 (42)
52.1 + 10.7 133 (63) 69 (31.5) 59 (27.9) 66 (31.2) 193 + 44 119 + 33 46 + 11 169 + 121 5.3 + 1.7 0.9 + 0.2 84 + 18 135 (63.9)
.073 .552 .294 .001 .001 .501 .134 .678 .067
Association of Glomerular Filtration Rate With Slow Coronary Flow in Patients With Normal to Mildly Impaired Renal Function
Angiology 2014, Vol. 65(9) 844-848 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714522106 ang.sagepub.com
Fatih Akin, MD1, Omer Celik, MD2, Burak Ayc¸a, MD3, Ahmet Arif Yalc¸ın, MD2, Ibrahim Altun, MD1, and Nuri Ko¨se, MD4
Abstract We evaluated the association between estimated glomerular filtration rate (eGFR) and slow coronary flow (SCF) in patients with normal to mildly impaired renal function; 211 patients with angiographically proven SCF and 219 controls were studied. Patients were categorized based on the angiographic findings as with or without SCF. We used the Modification of Diet in Renal Disease equation to calculate eGFR. The frequency of mildly decreased eGFR, serum uric acid levels, and eGFR was higher in the SCF group. Patients with mildly impaired renal function had higher thrombolysis in myocardial infarction frame counts in 3 major coronary arteries. In logistic regression analysis, uric acid (odds ratio [OR] ¼ 1.323, 95% confidence interval [CI] ¼ 1.109-1.572, P ¼ .002) and eGFR (OR ¼ 0.972, 95% CI ¼ 0.957-0.987, P < .001) were independent correlates of SCF. In conclusion, eGFR was significantly correlated with SCF in patients with normal to mildly impaired renal function. Keywords slow coronary flow, renal function, glomerular filtration rate, uric acid
Introduction
Study Population
Slow coronary flow (SCF) is an angiographic finding characterized by slow progression of contrast in the coronary arteries in the absence of obstructive coronary disease.1 The incidence of SCF ranges between 1% and 7% among patients who undergo coronary angiography.2,3 The underlying pathophysiological mechanisms and the clinical importance of SCF are not clearly defined. Some mechanisms that are possibly involved in the SCF include small-vessel dysfunction,4 diffuse atherosclerosis,5 inflammation,6 endothelial dysfunction,7 and increased platelet aggregability.8 Moreover, SCF is associated with increased cardiovascular (CV) mortality.9 Chronic kidney disease is recognized as a CV risk factor.10 Several studies suggest that mildly decreased estimated glomerular filtration rate (eGFR) is associated with increased rates of death from CV diseases.11,12 Yilmaz and Yalta13 have shown that impaired kidney function with the exclusion of those with severe renal dysfunction is associated with impaired thrombolysis in myocardial infarction (TIMI) flow. Another study showed that coronary TIMI flow is impaired in patients with end-stage renal disease (ESRD).14 However, there have been no studies investigating the association between mildly decreased eGFR and SCF. Therefore, we evaluated the association between mildly decreased eGFR and SCF.
Patients who underwent coronary angiography between March 2009 and August 2013 were evaluated for possible inclusion in the study. A total of 211 consecutive patients with SCF and 219 age- and gender-matched patients (control group) were included in the present study after the following exclusions: history of coronary artery disease (CAD) or sign of CAD on coronary angiograms, valvular heart disease, congestive heart failure, moderate and severely decreased eGFR based on the Modification of Diet in Renal Disease (MDRD) definition, concomitant inflammatory diseases, and neoplastic diseases. Patients taking uric acid-lowering agents were also excluded from the study. Detailed physical examination and an electrocardiogram were performed in all patients. The clinical risk 1
Department of Cardiology, Mug˘la Sitki Kocman University School of Medicine, Mugla, Turkey 2 Department of Cardiology, Mehmet Akif Ersoy Chest and Cardiovascular Surgery Education and Research Hospital, Istanbul, Turkey 3 Department of Cardiology, Bag˘cilar Education and Research Hospital, Istanbul, Turkey 4 Department of Cardiology, Mug˘la Yucelen Hospital, Mugla, Turkey Corresponding Author: Fatih Akin, Department of Cardiology, Mug˘la Sitki Kocman University School of Medicine, Mugla, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 10, 2015
Akin et al
845
factors for the patients, such as age, gender, hypertension (HT), diabetes mellitus (DM), history of hyperlipidemia, and smoking status, were noted. The local ethical committee approved the study protocol.
Definitions Hypertension was defined as a blood pressure 140/90 mm Hg or antihypertensive drug use. The DM was defined as fasting blood glucose 126 mg/dL on 2 occasions or being on treatment. Current smokers were defined as having a history of smoking within the past year. The assessment of renal function was based on the MDRD eGFR equation.15 According to the MDRD criteria, normal eGFR was defined as 90 mL/min/1.73 m2 and mildly decreased eGFR was defined as 60 to 89 mL/min/1.73 m2.
Evaluation of Coronary Blood Flow Coronary angiography was commonly indicated because of clinical symptoms or results of noninvasive tests that suggested myocardial ischemia. Coronary angiography was performed using the standard Judkins technique. During coronary angiography, an iopromide contrast medium (Ultravist 370; Schering AG, Berlin, Germany) was manually injected (6-10 mL of contrast agent at each standard views using right and left, and cranial and caudal angulations). Coronary flow rates of all patients were documented by the TIMI frame count (TFC) method, with cineangiography at 25 frames/sec. The TFC was determined for each major coronary vessel, by 2 trained cardiologists, according to the method first described by Gibson et al.16 Both investigators were blinded to the clinical details of the individual case. The TFCs of the left anterior descending (LAD) and circumflex (Cx) arteries were assessed in either the right anterior oblique projection with caudal angulations or the left anterior oblique projection with cranial angulations and that of right coronary artery (RCA) usually in straight left anterior oblique projection. Since the LAD coronary artery is usually longer than the RCA and the Cx, and the TFC for this vessel is often higher, the LAD frame counts were corrected by dividing by 1.7. Patients with a TFC of greater than 2 standard deviations from the normal published range16 for any 1 of the 3 vessels (40.6 frames for LAD, 29.8 frames for Cx, and 27.3 frames for RCA) were considered to have SCF.
Laboratory Measurements A fasting venous blood sample was obtained in the morning before coronary angiography. Levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in serum were measured using an Abbott Aeroset autoanalyzer with original kits (Abbott Laboratories, Abbott Park, Illinois). Low-density lipoprotein cholesterol (LDL-C) levels were calculated using the Friedewald equation. Serum uric acid (SUA) levels were measured using an enzymatic colorimetric test on a Roche/Hitachi analyzer (Roche/Hitachi Modular Analytics, Roche Diagnostics, GmBH, Mannheim, Germany). Hemoglobin and other hematologic parameters
Table 1. Baseline, Clinical, and Laboratory Characteristics of SCF and Normal Flow Groups.
Age, years Male gender, n (%) Hypertension, n (%) Diabetes, n (%) Smoking, n (%) Total cholesterol, mmol/L LDL cholesterol, mmol/L HDL cholesterol, mmol/L Triglyceride, mmol/L Uric acid, mg/dL Creatinine, mg/dL eGFR, mL/min/1.73 m2 Mildly decreased eGFR, n (%) Medications, n (%) Aspirin b-Blocker ACEI or ARB Statin Diuretic
Normal Flow Group n ¼ 219
SCF Group n ¼ 211
P
53.6 + 8.6 131 (59.8) 65 (29.6) 32 (14.6) 37 (16.8) 198 + 42 124 + 37 47 + 13 149 + 71 4.4 + 1.4 0.8 + 0.1 95.7 + 19 92 (42)
52.1 + 10.7 133 (63) 69 (31.5) 59 (27.9) 66 (31.2) 193 + 44 119 + 33 46 + 11 169 + 121 5.3 + 1.7 0.9 + 0.2 84 + 18 135 (63.9)
.073 .552 .294 .001 .001 .501 .134 .678 .067
