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J Thorac Cardiovasc Surg 2005;129:330-335
© 2005 The American Association for Thoracic Surgery
Surgery for Acquired Cardiovascular Disease |
a Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
b Department of Cardiology, Bernhoven Hospital, Veghel, The Netherlands
c Department of Cardiology, University Hospital Groningen, Thorax Center, Groningen, The Netherlands
d Department of Cardiothoracic Surgery, St Antonius Hospital, Nieuwegein, The Netherlands
Received for publication May 3, 2004; revisions received June 14, 2004; accepted for publication June 21, 2004. * Address for reprints: Ruud M. A. van de Wal, MD, PharmD, Department of Cardiology, St Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein, The Netherlands (E-mail: r.wal{at}antonius.net).
| Abstract |
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METHODS: In 358 patients who underwent isolated saphenous vein aortacoronary artery bypass grafting, estimated glomerular filtration rates were calculated with the Cockroft-Gault equation (GFRc). Patients were categorized into 2 groups (group 1, GFRc >71.1 mL · min1 · 1.73 m2; group 2, GFRc <71.1 mL · min1 · 1.73 m2). Multivariate Cox proportional hazard analyses were performed to determine the independent prognostic value of GFRc.
RESULTS: During a median follow-up of 18.2 years, 233 patients (65.1%) died. Patients who died had lower GFRc and were older. Multivariate analysis demonstrated that total mortality in patients with lower GFRc was significantly increased (lower GFRc group vs normal GFRc group: hazard ratio, 1.44; P = .019). Lower GFRc was also an independent predictor of cardiac mortality (hazard ratio, 1.51; P = .032). No significant differences were observed between groups in the occurrence of myocardial infarction and the need for reintervention.
CONCLUSIONS: Our study demonstrates that after long-term follow-up, preoperative mild renal dysfunction is an independent predictor of long-term (cardiac) mortality in patients who undergo coronary artery bypass grafting.
Patients with chronic renal failure are known to have an increased risk of cardiovascular disease.2,3 In addition, outcome after coronary bypass surgery of patients with end-stage renal disease is poor, and in this group a 5-year survival of less than 50% has been observed.4 Anderson and colleagues5 demonstrated that patients with mild renal dysfunction are predisposed to adverse 30-day outcomes after coronary artery bypass surgery. However, no studies assessed the influence of mild preoperative kidney dysfunction on long-term outcome after coronary bypass surgery. Therefore, we aimed to identify the significance of renal function as a predictor of long-term clinical outcome after coronary bypass surgery.
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Measurement of serum creatinine
Serum creatinine was measured with standard techniques in the clinical chemistry laboratory of our institution from blood samples drawn the week before surgery. Serum creatinine then was used to calculate GFRc by using the Cockcroft-Gault equation [(140age in years ) x (weight in kg)]/(72 x serum creatinine in mg/dL), multiplied by 0.85 in women. This equation is closely correlated with measured creatinine clearance (correlation coefficient, 0.83) and gives a more accurate assessment of renal function than serum creatinine alone.7
Statistical analysis
In our analysis we categorized GFRc into quintiles, and the hazard ratios were calculated for the lower GFRc quintiles compared with the (reference) highest GFRc group. Univariate Cox proportional hazard analysis demonstrated that the lowest 2 quintiles and the highest 3 quintiles showed similar hazard ratios. Subsequently, the patients were categorized into 2 groups (group 1: GFRc >71.1 mL · min1 · 1.73 m2, quintiles 3, 4, and 5; group 2: GFRc <71.1 mL · min1 · 1.73 m2, quintiles 1 and 2). Age was dichotomized in a similar manner; this resulted in 2 groups with a cutoff point of 54.7 years.
To identify prognostic covariates that might have been responsible for a difference in survival time between groups, survival curves were estimated by the method described by Kaplan and Meier from the following variables: presence of left main vessel disease, left ventricular function, number of vessels involved, completeness of revascularization, preoperative diabetes mellitus, preoperative cholesterol, number of distal anastomoses, preoperative smoking behavior, and hypertension. The log-rank test was used to calculate the statistical significance of differences in survival curves between groups. All variables with a significance level of P < .10 in this univariate test were included in a multivariate model proposed by Cox. The clinical events studied were overall mortality, cardiac mortality, acute myocardial infarction, and reintervention. Cardiac death was defined as death from a documented cardiac cause or death from an unknown cause. End points were scored in an hierarchical manner.8 All statistical analyses were performed with SPSS software (version 11.0; SPSS Inc, Chicago, Ill), and all reported P values are 2 sided.
| Results |
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| Discussion |
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2.0 mg/dL) carry significant operative risks, require prolonged hospital stays, and have a higher risk of dying within 3 years after coronary surgery.15 Nakayama and colleagues13 demonstrated that in a group of patients with a preoperative serum creatinine level of 1.5 mg/dL or greater (
133 µmol/L), the 10-year actuarial survival was significantly lower than in a group of patients with normal serum creatinine levels (<1.0 mg/dL; <88 µmol/L). Most patients in our population had a milder preoperative renal dysfunction than described in these studies, yet this parameter was still an independent predictor for mortality. It is interesting to note that Kaplan-Meier analysis clearly demonstrated that differences between GFR groups occurred only after approximately 10 years of follow-up. Possibly, this mirrors an accelerated rate of atherosclerosis, although in our population no difference in myocardial infarction was observed between groups. Several explanations have been proposed for the association between renal dysfunction, cardiovascular disease, and mortality.3,16,17 First, renal dysfunction is often associated with the presence of other cardiovascular risk factors, such as hypertension and diabetes. In these cases, renal dysfunction and cardiovascular morbidity would both be the results of end-organ damage. However, the effect of renal function on mortality in this study was independent of other known cardiovascular risk factors. Second, renal dysfunction might be the direct effect of cardiac dysfunction. In patients with a reduction of cardiac output, there is a decline in renal perfusion and an activation of compensatory mechanisms, which leads to renal function impairment.18,19 In these cases, renal dysfunction is a reflection of the cardiac function and may therefore be used as a risk marker for cardiovascular morbidity and mortality.20 In our patients, this mechanism probably does not play a role, because only a few patients had a significantly reduced left ventricular systolic function. Finally, renal dysfunction also has a negative effect on lipids, oxidative stress, homocysteine, and fibrinogen; this could lead to endothelial dysfunction.21 However, the question of whether endothelial dysfunction is the connecting bond between cardiovascular risk factors and renal dysfunction remains to be answered.
Patients receiving venous coronary bypass grafts often need reintervention and also have a worse prognosis compared with patients receiving arterial bypass grafts.22 Angiographic and necropsy studies have found evidence of accelerated atherosclerosis in saphenous vein conduits, possibly as a result of chronic endothelial activation.23 Nowadays arterial grafts are preferred to venous grafts, yet venous conduits continue to be used in a large proportion of coronary artery bypass grafting patients. Consequently, it is important to identify all patients at risk.
Limitations
This was a post hoc analysis of prospective data. Therefore, the results and conclusions are subject to the limitations inherent to such analysis. However, the principal variables of interestserum creatinine and deathare objective measures. The Cockroft-Gault equation is an estimate of the GFR and might lead to an overestimation of these parameters. Because this estimation was used for all patients and because GFR was an independent predictor of poor outcome, this should not affect our conclusions. Furthermore, GFR is only a surrogate marker for kidney function. In patients with an impaired GFR, no conclusions can be drawn concerning the etiology of the problem. Our study is also limited by a lack of data on the progression of renal impairment during follow-up. Finally, the study is limited by the number of (mainly white) patients participating and the fact that they were all in the same hospital.
Conclusion
This study demonstrates that preoperative mild renal dysfunction is an important independent risk marker of long-term survival in patients after coronary bypass surgery.
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