Eur J Cardiothorac Surg 2008;33:198-202. doi:10.1016/j.ejcts.2007.11.002
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Impact of estimated glomerular filtration rate on the 15-year outcome after coronary artery bypass surgery
Olli-Pekka Kangasniemi,
Muhammad Ali Asim Mahar,
Elsi Rasinaho,
Antti Satomaa,
Valentina Tiozzo,
Martti Lepojärvi,
Fausto Biancari*
Division of Cardio-thoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, Oulu, Finland
Received 20 May 2007;
received in revised form 30 October 2007;
accepted 5 November 2007.
* Corresponding author. Address: Division of Cardio-thoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, P.O. Box 21, 90029 Oulu, Finland. Tel.: +358 8 315 2813/40 7333973; fax: +358 8 315 2577. (Email: faustobiancari{at}yahoo.it).
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Abstract
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Objective: The aim of the present study was to evaluate the impact of estimated glomerular filtration rate (eGFR) on the 15-year outcome after coronary artery bypass surgery (CABG) in a community-wide population study. Methods: Eight hundred and eighty-two patients who underwent CABG were included in this study. eGFR was estimated by the modified Modification of Diet in Renal Disease study equation. Results: Among 30-day operative survivors, patients with eGFR < 60 ml/min/1.73 m2 had significantly poorer overall survival (at 5, 10 and 15 year, 84.7%, 63.5% and 43.8% vs 92.8%, 77.6% and 58.3%, respectively, p
< 0.0001). eGFR (HR 0.989, 95% CI 0.981–0.997, as well as eGFR < 60 ml/min/1.73 m2: HR 1.470, 95% CI 1.092–1.979) was an independent predictor of late all-cause mortality only when patients’ age was excluded from the regression model. This was probably due to strong impact of age on eGFR. eGFR (HR 0.987, 95% CI 0.975–0.998, as well as eGFR < 60 ml/min/1.73 m2; HR 1.612, 95% CI 1.086–2.395) was an independent predictor of cardiovascular mortality secondary to ischemic heart disease or ischemic stroke. eGFR (HR 0.991, 95% CI 0.983–0.999, as well as eGFR < 60 ml/min/1.73 m2: HR 1.396 95% CI 1.031–1.891) was an independent predictor of cardiovascular mortality and morbidity (myocardial infarction, stroke, need for redo CABG or PCI). When both preoperative serum creatinine and eGFR were included in the regression model, only eGFR was predictive of all-cause mortality, cardiovascular mortality and combined cardiovascular mortality and morbidity. Conclusions: This study showed that an eGFR < 60 ml/min/1.73 m2 is an important determinant of long-term outcome after isolated CABG. Since its predictive value seems to be superior to serum creatinine, eGFR may be useful to identify those patients undergoing CABG with subclinical chronic kidney disease.
Key Words: Coronary artery bypass surgery • Creatinine • Glomerular filtration rate • Renal failure • Survival
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1. Introduction
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Renal failure has been largely shown to be a major determinant of development of cardiovascular disease and of late mortality [1]. Serum creatinine level is recognized as a major risk factor in patients undergoing cardiac surgery and it is included in the current most accurate operative risk scoring methods [2–5]. However, the superiority of estimated glomerular filtration rate (eGFR) over serum creatinine as a measure of renal function has been recently claimed [6]. Indeed, eGFR has been shown to be a major determinant of outcome after coronary artery bypass surgery (CABG) [7–10]. The aim of the present study was to evaluate the impact of different degrees of kidney disease as measured by eGFR on the 15-year outcome after coronary artery bypass surgery (CABG) in a community-wide population study.
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2. Material and methods
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This study includes a consecutive series of 916 patients who were residents of Oulu and who were referred for isolated CABG to the Division of Cardio-thoracic and Vascular Surgery of the Oulu University Hospital, Oulu, Finland, from January 1990 to August 1999. Patients operated later on were not included in this study as the methods of measurement of serum creatinine have changed since September 1999. After excluding patients in whom preoperative serum concentrations of creatinine were lacking, 882 patients were included in the final analysis. Other exclusion criteria were: residency in towns other than Oulu, preoperative dialysis and any other cardiac procedure performed simultaneously. Only Oulu inhabitants were included in the study to better estimate the incidence of cardiovascular morbidity and need for redo CABG and/or percutaneous coronary intervention after CABG.
Preoperative clinical data of these patients according to different classes of chronic kidney disease classes [13] are reported in Table 1
. In this series, only 23 patients have been operated employing the off-pump technique. The latter technique has been extensively adopted in our division since 2002. All the other patients have been operated on using antegrade and retrograde cold blood cardioplegia with single aortic cross-clamping.
Data were collected retrospectively from records including files from all departments of this hospital. Our institution is a tertiary referral hospital and patients requiring any surgical procedure as well as having any major cardiovascular event are referred to our hospital. Dates and causes of death have been retrieved from a national registry (Tilastokeskus).
All serum creatinine concentrations were measured with the Jaffé method (CREA, Hico Creatinine, Boehringer Mannheim, no. 1040847) on a BM/Hitachi 911 Autoanalyzer (Roche Diagnostics). Preoperative glomerular filtration rate was estimated according to the modified Modification of Diet in Renal Disease study equation [11,12]: eGFR (ml/min/1.73 m2) = 186 x (serum creatinine (mg/dl))–1.154
x (age)–0.203
x 0.742 (if the subject is female) x 1.212 (if the subject is black). Severity of renal failure was classified according to the chronic kidney disease classification [13]: class 1 (normal): eGFR > 90 ml/min/1.73 m2; class 2 (mild): eGFR 60–89 ml/min/1.73 m2; class 3 (moderate): eGFR 30–59 ml/min/1.73 m2; class 4 (severe); eGFR15–29 ml/min/1.73 m2, class 5 (kidney failure): eGFR < 15 ml/min/1.73 m2.
Outcome end-points of this study were all-cause mortality, cardiovascular mortality secondary to ischemic heart disease and combined cardiovascular mortality and morbidity. Cardiovascular morbidity refers to myocardial infarction, ischemic stroke, and need for redo coronary surgery and/or percutaneous coronary intervention.
2.1 Statistical analysis
Statistical analysis was performed using an SPSS statistical software (SPSS v. 14.0.1, SPSS Inc., Chicago, IL, USA). Continuous variables are reported using the mean ± standard deviation. The Pearson's chi-square test, Fisher exact test, the Mann–Whitney test and the Kruskal–Wallis’ tests were used for univariate analysis. Survival rates were estimated by the Kaplan–Meier's method with the log-rank test. Cox regression, with the help of backward selection, was used for multivariate analysis including those variables with a p
< 0.05 at univariate analysis. Receiver operating characteristics (ROC) curve was used to estimate the predictive value of eGFR. A p
< 0.05 was considered statistically significant.
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3. Results
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The 30-day mortality rate in this series was 2.2%. eGFR as classified in different stages was associated with increased risk of immediate postoperative morbidity and mortality (Table 2
). The area under the ROC curve, however, was not optimal for predicting 30-day postoperative death (AUC 0.617). Preoperative serum levels of creatinine were a slightly better predictor of 30-day postoperative mortality (AUC 0.642). However, when eGFR < 60 ml/min/1.73 m2 (p
= 0.02) and serum creatinine >150 mg/dl (p
= 0.2) and serum creatinine >200 mg/dl (p
= 0.06) were chosen as cut-off values, the former was the only one significantly associated with 30-day postoperative mortality.
The mean follow-up period was 10.2 ± 3.7 years. Predictors of late outcome among operative survivors are reported in Table 3
. Among 30-day operative survivors, advanced stages of renal failure were associated with decreased 15-year overall survival as shown in Fig. 1
. Poor late overall survival was particularly evident among patients with eGFR < 60 ml/min/1.73 m2 (at 5, 10 and 15 year, 84.7%, 63.5% and 43.8% vs 92.8%, 77.6% and 58.3%, respectively, SE < 0.058, p
< 0.0001).
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Fig. 1. Kaplan–Meier estimates of freedom from fatal and non fatal cardiovascular events in patients with different stages of kidney disease (normal: eGFR > 90 ml/min/1.73 m2; mild: eGFR 60–89 ml/min/1.73 m2; moderate: eGFR 30–59 ml/min/1.73 m2; severe: eGFR < 30 ml/min/1.73 m2) (p
< 0.0001).
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When adjusted for all variables with a p
< 0.05 at univariate analysis (Table 3), eGFR was not an independent predictor of late all-cause mortality. When patients’ age was excluded from the model, as it greatly influences eGFR, continuous eGFR (p
= 0.005, HR 0.989, 95% CI 0.981–0.997) as well as eGFR < 60 ml/min/1.73 m2 (p
= 0.01, HR 1.470, 95% CI 1.092–1.979) were independent predictors of all-cause mortality.
eGFR was an independent predictor of cardiovascular mortality secondary to ischemic heart disease or ischemic stroke (p
= 0.03; HR 0.987, 95% CI 0.975–0.998), even when included into the regression model as dichotomous variable (eGFR < 60 ml/min/1.73 m2; p
= 0.02, HR 1.612, 95% CI 1.086–2.395).
eGFR was an independent predictor of cardiovascular mortality and morbidity (myocardial infarction, stroke, need for redo CABG or PCI) (p
= 0.03; HR 0.991, 95% CI 0.983–0.999). Similarly, eGFR < 60 ml/min/1.73 m2 was also an independent predictor of late cardiovascular mortality and morbidity (p
= 0.03, HR 1.396 95% CI 1.031–1.891).
When both preoperative serum creatinine and eGFR were included into the regression model, only eGFR was a predictor of all-cause mortality (p
< 0.0001, HR 0.983, 95% CI 0.975–0.991), cardiovascular mortality (p
< 0.0001, HR 0.972, 95% CI 0.961–0.983) and combined cardiovascular mortality and morbidity (p
< 0.0001, HR 0.984, 95% CI 0.977–0.992).
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4. Discussion
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This study confirmed the major impact of subclinical degrees of renal failure on the immediate and late outcome of patients undergoing CABG. Recently, Holzmann et al. [8] have shown the impact of the CKD classes on the 5-year all-cause mortality and myocardial infarction after CABG. Previously, similar results have been reported by van de Wal et al. [10] who estimated the GFR by the Cockroft–Gault equation. Indeed, long-term survival after surgical revascularization of the lower limb has also been shown to be significantly lower in patients with an eGFR < 60 ml/min/1.73 m2, and it was particularly dismal among those in CKD class 4 and 5 [14].
We have observed that eGFR is superior to serum creatinine to predict late all-cause mortality as well as cardiovascular mortality and morbidity. This observation along with the finding of a clear impact of an eGFR < 60 ml/min/1.73 m2, make the latter cut-off value a relevant and clinically easy-to-use prognostic marker. Indeed, an eGFR of less than 60 ml/min/1.73 m2 has previously been shown to be associated with an increased risk of renal failure, cardiovascular disease and premature death [6]. Identification of patients with mild impaired renal function undergoing cardiac surgery is not only valuable for operative risk assessment, but also highly recommended to avoid the severe complications associated with decreased kidney function. For example, this particular subset of patients may most benefit from off-pump coronary artery surgery [15]. Furthermore, early referral of these patients to the nephrologist is currently recognized to be of great importance in improving their late outcome [16,17]. Reporting of eGFR values from clinical laboratories has been suggested in order to improve physicians’ recognition of chronic kidney disease [18]. Specific values should be reported only for values of eGFR < 60 ml/min/1.73 m2 as higher values are associated with significant bias [6].
The significantly increased risk of ischemic heart and cerebrovascular events in patients with eGFR indicates that an aggressive treatment approach for cardiorenal protection is needed. The increased age, the decreased left ventricular ejection fraction as well as the increased prevalence of extracardiac arteriopathy, diabetes, hypertension and history of stroke indicate that these patients have a number of established comorbidities which suggest a reduced expectancy of life despite additional more aggressive medical treatment. We believe that adequate measures for secondary prevention of atherosclerosis were well established during the study period as these patients were residents in the town of Oulu and they were mostly treated at our institution which is a referral centre for cardio-thoracic and vascular surgery as well as for cardiology, nephrology and neurology. Undoubtedly, a more aggressive policy of screening for subclinical renal failure and referral to the nephrologist was likely not carried out. Thus, the potential value for a more aggressive policy of investigation and treatment of these patients remains unknown. Indeed, there are some risk factors such as patients’ age which cannot be modified. Age is one of the most important predictor of immediate and late outcome after cardiac surgery as confirmed in this study. Age is also a major determinant of increased eGFR and this may explain why the latter was not an independent predictor of all-cause mortality when age was included in the regression model. Furthermore, age is an important risk factor for non-cardiovascular mortality. On the other hand, eGFR showed that its impact on late cardiovascular mortality and morbidity can be independent from age (Table 3).
In conclusion, this community-wide study showed that an eGFR < 60 ml/min/1.73 m2 is a major determinant of long-term all-cause and cardiovascular mortality and morbidity after CABG. Since its predictive value seems to be superior to serum creatinine, eGFR may be useful to identify those patients undergoing CABG with subclinical chronic kidney disease.
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Abstract
1. Introduction
