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Ann Thorac Surg 2000;69:30-35
© 2000 The Society of Thoracic Surgeons

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Original Articles

Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting

^a Department of Surgery, Columbia University College of Physicians and Surgeons, New York City, New York, USA

Address reprint requests to Dr John, Division of Cardiothoracic Surgery, Milstein Hospital, Room 7-435, 177 Fort Washington Ave, New York, NY 10032
e-mail: ranjitj{at}pol.net

Presented at the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

	Abstract

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
Background. Stroke complicates the postoperative course in 1% to 6% of patients undergoing coronary revascularization. There has been no large scale mandatory database reporting on the incidence of stroke after coronary revascularization.

Methods. A multicenter regional database from the Bureau of Health Care Research Information Services, New York State Department of Health, on 19,224 patients who underwent coronary revascularization in 31 hospitals within New York State during 1995 was analyzed to determine the risk factors for postoperative stroke.

Results. The incidence of postoperative stroke was 1.4% (n = 270). Hospital mortality for patients who had a stroke was 24.8%, compared with 2.0% for the rest of the patient population. Postoperative stroke increased the hospital length of stay threefold (27.9 ± 1.9 versus 9.1 ± 0.9 days, p < 0.0001). Multivariable logistic regression identified the following variables to be significantly associated with a postoperative stroke: calcified aorta (p < 0.0001; odds ratio [OR], 3.013), prior stroke (p = 0.0003; OR, 1.909), age (p < 0.0001; OR, 1.522 per 10 years), carotid arterial disease (p = 0.002; OR, 1.590), duration of cardiopulmonary bypass (p = 0.0004; OR, 1.27 per 60 minutes), renal failure (p = 0.0062; OR, 2.032), peripheral vascular disease (p = 0.0157; OR, 1.62), cigarette smoking (p = 0.0197; OR, 1.621), and diabetes mellitus (p = 0.0158; OR, 1.373).

Conclusions. Postoperative stroke increases mortality and length of stay after coronary revascularization. Several risk factors can be identified, and some of these factors are potentially amenable to intervention, either before or during coronary revascularization, and should also influence patient selection.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
The benefits of coronary artery bypass grafting (CABG) over medical therapy and catheter-based interventional procedures are limited by the complications of the operation. Although the overall incidence of complications after CABG has decreased, the incidence of postoperative stroke remains unchanged and is reported in 0.8% to 6% of patients after CABG [1]. Postoperative stroke also remains a catastrophic and costly complication of CABG, with a reported 21% mortality and mean hospital stay of 25 days among the survivors [2]. This mandates that additional interventions be developed in an attempt to decrease the incidence of stroke after coronary revascularization.

Perioperative hypotension, hypoperfusion, and thromboembolism are the main intraoperative factors associated with a postoperative stroke [3, 4]. In addition, several groups of patients are known to be at high risk for developing stroke after CABG [5]. These include older patients, patients with carotid artery disease, aortoiliac arterial disease, a recent myocardial infarction, and prior history of a cerebrovascular event.

Although there are numerous reports on postoperative strokes after coronary revascularization, most are based on single-institution patient populations. A multicenter study would be more accurate given the different referral patterns and patient populations at each institution. This study was not only multicenter-based but it also encompassed all 31 institutions that performed cardiac surgery within a defined region. The study group likely provided an adequate sampling of the CABG surgical patient population.

Identification of predisposing factors can allow preoperative risk stratification and can facilitate improved patient selection, both significant considerations when patients being referred for myocardial revascularization are older, higher risk cases, and have systemic arteriosclerotic disease. This information may also potentially reduce the risk of a stroke by providing an opportunity for medical or surgical intervention before or during the operation.

The goals of the present study were to determine the incidence of stroke after CABG and to identify the preoperative and intraoperative factors associated with the development of a stroke. In addition, the impact of a postoperative stroke on length of stay and hospital mortality were evaluated.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
Patient population
An evaluation was performed of all patients undergoing CABG within the state of New York during 1995. Data source was the New York State Cardiac Surgery Database, which is a prospectively collected mandatory registry of all patients undergoing cardiac surgery within the state collected by the Bureau of Health Care Research and Information Services, New York State Department of Health. Only patients who underwent coronary revascularization as the sole procedure were included in this study. Excluded were any patients who had a combined CABG and valvular or congenital heart procedures.

Risk factors
A postoperative stroke was defined as a transient or permanent new neurologic deficit occurring within 24 hours after operation. A total of 26 variables were evaluated in this study. Demographic and preoperative variables included age, sex, priority of surgery (elective, urgent, and emergent), prior myocardial infarction, previous stroke, preexisting carotid artery disease, peripheral vascular disease, hypertension, diabetes mellitus, renal failure, chronic pulmonary obstructive disease, hepatic failure, prior cardiac surgery, ventricular arrhythmias, smoking within 1 year, and cardiac ejection fraction. The perioperative factors evaluated were the use of intravenous nitroglycerin, use of thrombolytic therapy within 7 days of CABG, hemodynamic stability of the patient, preoperative use of an intraaortic balloon pump, use of intravenous heparin within 48 hours of CABG, presence of a calcified aorta, number of coronary vessels diseased or bypassed, and the duration of cardiopulmonary bypass (CPB) (see Appendix).

Statistical analysis
Data were first examined univariately by the Student’s t test for continuous variables and Fisher’s exact test for discrete data. For the multivariable analysis, variables with a p value less than 0.25 were entered into a logistic regression analysis model [6]. This model is a multiple regression analysis for examining dichotomous outcomes such as stroke versus no stroke and their potential associated risk factors by modeling a linearized function of a set of covariates. The interpretation of a risk factor allowed into the final model with a p value less than 0.05 is that it is an independent risk factor associated with the event, over and above other potential risk factors included in the equation.

Given a set of data, this logistic regression algorithm can compute a calculated multivariable risk factor equation, yielding p values assigned to one or more beta (slope) coefficients and their corresponding independent predictor variables (x covariates).

The final multivariable logistic regression equation may be used to predict the probability of stroke using the following:

Where is the probability of stroke; ßo is a constant; ß₁, ß₂, ... ß_p are regression coefficients; and x₁, x₂, ... x_p are variables in the equation.

Using the equation above, we may predict the probability of stroke by answering the following question, for example: what is the probability of a 60-year-old white man with diabetes and renal failure having a stroke after coronary revascularization? These patient-specific characteristics are then substituted into the prediction equation to estimate the corresponding probability of stroke for this particular patient.

For all statistical analyses, data were analyzed using the SAS System software (SAS Institute, Inc, Cary, NC).

	Results

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
A total of 19,224 patients underwent CABG as the sole cardiac surgical procedure in 1995. One hundred twenty-one surgeons at 31 hospitals in New York State performed these operations. There were 13,797 men (71.7%) and 5,427 women (28.3%). The mean age of these patients undergoing CABG was 65 ± 10 years (range, 25 to 95 years). Among these 19,224 patients, there were 270 cases of postoperative strokes (incidence, 1.4%).

Univariate analysis of the risk factors that influence the development of a stroke are represented in Table 1. Demographic and preoperative factors that were found to be significant included age greater than 70 years, previous history of a stroke, peripheral vascular disease, hypertension, chronic renal failure, and diabetes mellitus. Perioperative factors that were found to be significant included absence of intravenous heparin 48 hours before CABG, presence of a calcified aorta, presence of multivessel disease (three vessels or more), and the duration of CPB.

The in-hospital mortality for patients who had a stroke was 24.8% compared with 2.0% for patients who did not develop a stroke (p < 0.001). In addition, of all in-hospital deaths in patients undergoing CABG, 14.8% had had a postoperative stroke.

	Comment

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
This study was undertaken to evaluate the risk factors for postoperative strokes among 19,224 patients who underwent coronary revascularization in all 31 hospitals that performed cardiac surgery within New York State during 1995. As such, the bias associated with differences in referral patterns and patient populations, as well as in patient management, were likely to be decreased.

The incidence of stroke was 1.4% in this study. Frye and associates [7] found the incidence of stroke to be 1.9% during the initial hospitalization for surgery in the Coronary Artery Surgery Study experience. In contrast, Roach and colleagues [2] reported the incidence of adverse cerebral outcomes after CABG to be 6.1%; however, half of the patients in the multicenter study primarily had deterioration in intellectual function, confusion, agitation, memory deficit, or disorientation. These neurologic deficits likely have multiple causes and risk factors different from the typical stroke. A further review of the literature showed that the incidence of stroke ranges from 1.6% to 4.3% among patients undergoing coronary revascularization [8–11]. The variation in the incidence of stroke is multifactorial, primarily relating to the differing patient populations that underwent CABG at different hospitals, and most likely reflects on the accuracy of reporting.

Several risk factors associated with the development of a postoperative stroke were identified in our study, including a calcified aorta, increasing age, prior history of a stroke, carotid and cerebrovascular disease, peripheral vascular disease, chronic renal failure, recent smoking history, and diabetes mellitus. A prolonged CPB time was also found to be a significant risk factor.

Most of the risk factors identified in this study correlated with those that have been identified in other studies. Those risk factors that have appeared repeatedly in other studies include older age, history of a previous stroke, arteriosclerotic ascending aortic disease, diabetes mellitus, renal failure, carotid and peripheral vascular disease, and prolonged CPB time. Risk factors that were not found in our study but have been inconsistently reported by others include previous coronary artery operation [10], unstable angina [10], history of pulmonary disease [10], hypertension [9], perioperative myocardial infarction [4], poor left ventricular function [4], and normothermic systemic perfusion [5]. One risk factor in our study that has not been reported previously is a recent smoking history. Once again, the variation in risk factors probably reflects different patient populations and study designs.

Not surprisingly, the common risk factors were found to be prevalent among those patients with generalized arteriosclerosis; this association suggests that a thromboembolic event may be important in the pathogenesis of postoperative strokes. An initial suggestion of this was noted in our univariate analysis (Table 1), which showed that the absence of anticoagulation therapy during the preoperative period was more frequent among the stroke patients.

Our study found that the most significant risk factor for a postoperative stroke was the presence of a calcific aorta, a finding not always detected before the operation. Therefore, the management of an arteriosclerotic aorta, especially a calcified one, is important in the overall surgical strategy to decrease the risk of a postoperative stroke after coronary revascularization [12, 13].

An increase in the incidence of strokes proportional to the duration of CPB was another finding in this study. Cerebral blood flow is known to decline with time during CPB and is probably related to a hypothermia-related decrease in cerebral metabolic rate [14]. The longer CPB times may also reflect a group of patients who were sicker and had more extensive coronary artery disease. The progressive decrease in cerebral blood flow compounded by a low flow state or hypotension after CPB may have contributed to the higher incidence of stroke in this setting. The recent application of minimally invasive techniques, especially the avoidance of CPB, may decrease the incidence of postoperative stroke. Although satisfactory midterm outcomes have been thus far obtained with minimally invasive techniques, long-term outcomes with larger numbers of patients are needed to determine its role in patients requiring myocardial revascularization. Nevertheless, there appears to be a select subgroup of patients, including older and high-risk patients, in whom minimally invasive techniques such as the avoidance of CPB may be applicable.

Patients who had a stroke in this study had an in-hospital mortality of 24.8% and a mean hospitalization of 27.9 days compared with 2.0% mortality and a mean hospitalization of 9.1 days for the nonstroke patients. This high mortality has been similarly reported by others and has not changed during the past decade [1, 2].

Despite the advantages obtained by performing a large multicenter study, there are several limitations to the present study. First, there are concerns with underreporting of strokes and completeness of data collection with this type of a multicenter registry. Although the Department of Health made a significant effort to verify the accuracy of the data, different individuals at each institution entered the information. Second, the diagnosis of a postoperative stroke was not standardized. The patients were evaluated by different physicians and by various diagnostic modalities. This may affect issues relating to sensitivity and selectivity in this study. Furthermore, neither information concerning the severity of the stroke nor information on intellectual function and cognitive changes was reported in this database. A third limitation involves the lack of any follow-up data except for hospital mortality and length of stay. As a result, no information was available concerning the status of neurologic deficits subsequent to the stroke. Despite these limitations, the study represents the only report on postoperative stroke after CABG that is inclusive of all patients undergoing CABG operation at each hospital within a region, incorporating institutions with different referral patterns, patient populations, and patient practices.

The Society of Thoracic Surgeons (STS) National Cardiac Surgery Database has been used to develop risk models of operative mortality and has been shown to be a reliable and statistically valid tool [15]. The 1997 STS National Database, involving a population of 174,806 patients undergoing CABG, identified a postoperative permanent stroke rate of 1.69%. Further, the mortality in patients experiencing a postoperative stroke was 25.6% as opposed to a mortality rate of 2.4% in patients who did not have a postoperative stroke [16]. The STS database also reports on the incidence of delirium (2.7%) and continuous coma more than 24 hours (0.5%) after CABG. However, no detailed risk factor identification for specific morbidities such as postoperative stroke is currently available from the STS database.

There remain several unanswered questions as to the strategies that need to be used based on the identification of these risk factors to decrease the occurrence of stroke after CABG. We and others have shown that off-pump CABG is being increasingly used for patients requiring coronary revascularization who are at high risk for the development of postoperative stroke as well as other complications resulting from CPB [17, 18]. The knowledge that a calcified arteriosclerotic aorta is especially a marker for the development of postoperative stroke has led to the use of several maneuvers that may result in safer aortic manipulation during operation. These include the use of intraoperative transepicardial echocardiography, pedicled coronary grafts, and sequential vein grafts, as well as the use of femoral cannulation. Further, the replacement of the ascending aorta using hypothermic circulatory arrest in addition to coronary revascularization has also been advocated [12, 13]. Strategies to treat coexistent carotid artery disease simultaneously with coronary revascularization may allow a reduction in the incidence of postoperative stroke [19]. Agents such as serine protease inhibitors, antioxidants, gangliosides, and glutamate receptor antagonists may have potential use by decreasing neuronal damage. Of these, only aprotinin has actually been shown to reduce the incidence of stroke in patients undergoing coronary revascularization [20].

In conclusion, despite advances in cardiac surgery that have led to an overall improvement in outcome after coronary revascularization, the incidence of stroke after CABG has remained constant. Postoperative stroke is a major contributor to mortality, prolonged hospitalization, and other adverse postoperative complications. Knowledge of the risk factors offers an opportunity to implement preoperative as well as intraoperative measures to reduce the occurrence of stroke and should influence patient selection. Older patients with arteriosclerotic disease of the aorta, especially the ascending aorta, and a prior history of cerebrovascular disease are at significant risk for a postoperative stroke after coronary revascularization.

	Acknowledgments

 
Mehmet C. Oz is an Irving Fellow of Columbia University.

	Appendix

Top Abstract Introduction Patients and methods Results Comment Appendix References

 
Preoperative chronic medical morbidity risk factors

1. Myocardial infarction (MI): Either clinical or electrocardiographic evidence was required for a diagnosis of previous MI. In patients having previously diagnosed MI, the duration since the most recent MI was noted. Transmural MI was diagnosed by the presence of new Q waves and a rise in creatine kinase heart muscle-specific isoenzyme to a level indicating MI.
   
2. Hypertension: A diagnosis of hypertension was made if a blood pressure more than 140/90 mm Hg was documented, there was a history of hypertension, or the patient was currently on antihypertensive medication.
   
3. Congestive heart failure, during admission for CABG: Congestive heart failure at New York Heart Association level III or IV occurring during this admission.
   
4. Congestive heart failure, before this admission: If the patient has been treated for congestive heart failure before this admission, but is not in congestive heart failure at level III or IV during this admission.
   
5. Stroke: A history of stroke, with or without residual defect.
   
6. Carotid/cerebrovascular disease: Patients who have greater than 50% cerebral artery obstruction, have a history of a nonembolic stroke, or have required an operation for such disease. A history of bruits or transient ischemic attacks was not sufficient evidence for carotid/cerebrovascular disease.
   
7. Peripheral vascular disease: (1) Patients who have significant vascular disease in the aorta or iliac arteries, or who have been previously operated for such disease; (2) Patients who have had prior revascularization of femoropopliteal vessels, have absent or diminished pulses, or in whom an attempt to insert a balloon-assist device fails because of diminished femoral arteries, or in whom an angiogram demonstrates a greater than 50% narrowing in a major femoral or popliteal vessel.
   
8. Chronic obstructive pulmonary disease: Patients who are functionally disabled, or require bronchodilator therapy, or have a forced expiratory volume in 1 second (FEV₁) less than 75% or less than 1.25 L, or have a PO₂ less than 60 mm Hg and a PCO₂ greater than 60 mm Hg on room air.
   
9. Malignant ventricular arrhythmia: Recurrent ventricular tachycardia or ventricular fibrillation requiring electrical defibrillation or the use of intravenous antiarrhythmic agents. This does not exclude a single episode of ventricular tachycardia or fibrillation occurring in the early phase of acute MI and responding well to treatment.
   
10. Diabetes: Patients with diabetes requiring either oral hypoglycemic agents or insulin.
    
11. Renal failure: Patients with a preoperative creatinine greater than 2.5% or patients with renal failure on chronic peritoneal or hemodialysis.
    
12. Hepatic failure: Patients with an established diagnosis of cirrhosis and with a bilirubin greater than 2 mg/dL and a serum albumin less than 3.5 g/dL.
    

Perioperative risk factors

1. Preoperative intraaortic balloon pump: If the patient arrives in the operating room with an intraaortic balloon pump or requires its insertion before the induction of anesthesia.
   
2. Emergency transfer to the operating room after diagnostic catheterization or percutaneous transcutaneous coronary angioplasty: If the patient requires immediate operation after a diagnostic catheterization or a percutaneous transcutaneous coronary angioplasty complicated by cardiovascular collapse that requires cardiopulmonary resuscitation en route to the operating room or resuscitation in the catheterization laboratory.
   
3. Previous percutaneous transcutaneous coronary angioplasty: If the patient had a percutaneous transcutaneous coronary angioplasty either during or before this admission.
   
4. Thrombolytic therapy: Use of thrombolytic therapy such as streptokinase, urokinase, or thromboplastin activator for the purpose of dissolving a coronary thrombosis within 7 days before surgery.
   
5. Hemodynamic instability: (1) Unstable: if the patient requires pharmacologic or mechanical support before or at the induction of anesthesia, (2) Shock: if the patient has systolic blood pressure less than 80 mm Hg and has evidence of poor end-organ perfusion (such as low urine output or depressed mentation).
   

	References

Top Abstract Introduction Patients and methods Results Comment Appendix References

 

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