Ann Thorac Surg 1998;65:377-382
© 1998 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Late Outcome of Coronary Artery Bypass Grafting in Young Versus Older Patients
Isabella Rohrer-Gubler, MD,
Urs Niederhauser, MD,
Marko I. Turina, MD
Division of Cardiovascular Surgery, Department of Surgery, University Hospital, Zurich, Switzerland
Accepted for publication July 17, 1997.
Dr Rohrer-Gubler, Sprecherstrasse 5, 8032 Zurich, Switzerland.
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Abstract
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Background. We compared long-term results of coronary artery bypass grafting between 1976 and 1988 in 176 patients 40 years old or younger with a matched control group of 176 patients 25 to 30 years older.
Methods. Mean age was 37.4 ± 2.7 years (± standard deviation) in the study group and 64.2 ± 2.9 years in the control group. Matching criteria were age, sex, left ventricular ejection fraction, number of bypass grafts, and year of operation.
Results. The study group had more smokers (p = 0.000) and more patients with hypercholesterolemia (p = 0.026), unstable angina (p = 0.003), and preoperative myocardial infarction (p = 0.009); fewer patients had hypertension (p = 0.000) and diabetes (p = 0.005) in this group than in the control group. The internal mammary artery was used in 31% of the study patients and in 30% of the controls. The actuarial survival rates after 5, 10, and 15 years were 92%, 86%, and 72% in the study group and 92%, 86%, and 66% in the control group (p = 0.202). Young age was a predictor of cardiac reoperation.
Conclusions. Late survival is similar for young and older patients, but the reintervention rate is higher in the younger group. The absence of unstable angina, a left ventricular ejection fraction greater than 0.45, and the use of internal mammary artery grafts increase survival in all patients.
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Introduction
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This report is a retrospective analysis of short-term and long-term results in patients 40 years or younger who underwent coronary artery bypass grafting (CABG) at the University Hospital of Zurich between 1976 and 1988. They were compared with a matched control group of older patients operated on in the same period. The aim of the study was to compare long-term mortality and morbidity in young versus older patients and to evaluate the presence of risk factors and their influence on outcome in both groups.
To investigate the long-term outcome, we selected patients who underwent operation 10 to 20 years ago, namely, between 1976 and 1988. On the one hand, we had a long follow-up. On the other hand, the operations were not done using techniques that are standard today. For example, only 31% of both groups received an internal mammary artery (IMA) graft. In addition, percutaneous transluminal coronary angioplasty (PTCA) [1] has probably decreased the number of young patients having CABG, and surgical revascularization is offered only to those with severe disease. Nevertheless, we wanted to analyze the long-term outcome for patients aged 40 years or less because little is known about the long-term results of CABG in young patients [2] [3].
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Patients and Methods
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Between January 1976 and December 1988, 176 patients 40 years of age or younger underwent isolated primary CABG at the University Hospital of Zurich. They formed the study group. The patients in the control group were 25 to 30 years older. They were selected for age and the following four matching criteria: sex, left ventricular ejection fraction, number of bypass grafts, and year of operation.
Definitions
Operative mortality (or early mortality) was defined as death within 30 days of CABG, even if the patient had been discharged from the hospital. Era of operation (before and after 1980) was dependent on changes in operative techniques (use of IMA grafts) and onset of PTCA. Freedom from reoperation was defined as freedom from cardiac reoperation, such as second or third CABG, heart transplantation, valve replacement, or ascending aorta graft. Angina class was defined by the New York Heart Association criteria. Left ventricular ejection fraction was identified by echocardiography or angiography and categorized as poor (0.45), fair (0.45 through 0.60), and good (0.60) for the purpose of multivariate analysis. Left main coronary artery disease and number of diseased vessels were determined by coronary angiography. Perioperative myocardial infarction was defined as cardiac enzyme elevation (level of myocardial-specific isoenzymes of creatine kinase greater than 10% of total creatine kinase value), electrocardiographic changes (development of new Q waves in serial postoperative electrocardiograms), and development of new hypokinesia or akinesia in serial echocardiograms after CABG during hospitalization.
Definitions of individual risk factors were as follows: smoking = more than one pack per day for more than 1 year before CABG; hypercholesterolemia = cholesterol level greater than 300 mg/dL; hypertension = diastolic blood pressure of 95 mm Hg or greater; diabetes mellitus = insulin-dependent or non–insulin-dependent; and positive family history = atherosclerotic coronary artery disease (CAD) in a first-degree relative.
Preoperative Data
Table 1 summarizes the preoperative data on the two groups. The study group had significantly more smokers and patients with hypercholesterolemia and significantly fewer patients with hypertension and diabetes. Table 2 shows the severity of the CAD in each group. Left ventricular ejection fraction was a matching criterion and therefore was similar in the two groups (p = 0.270). One-vessel disease was noted significantly more often in the study group than in the control group.
Operation and Follow-up
A summary of the operative data is provided in Table 3. All patients received saphenous vein grafts only or a single IMA-graft with or without associated vein grafts or bilateral IMA grafts. No single or bilateral IMA grafts were used before 1980.
At follow-up, repeat physical examination, electrocardiograms, stress tests, and coronary angiography were done. Follow-up information was compiled from the case records of patients, routine mailed questionnaires, contact with each patient’s personal physician, and death certificates. Four patients (1 in the study group and 3 in the control group) were lost to follow-up. All other survivors were contacted between June 1994 and January 1995. Patients in the study group were followed for a mean of 8.8 ± 3.3 years (± standard deviation) (range, 0 to 18.5 years), and patients in the control group, a mean of 8.2 ± 3.4 years (0 to 19.3 years).
Statistical Methods
Actuarial survival and intervention-free survival were determined by the Kaplan-Meier method. Comparisons between groups were performed with the Cox test. Important risk factors were first identified using univariate analysis of the data. Categoric data were compared by the McNemar 
2 test and continuous data, by the Mann-Whitney U test. If there were fewer than 5 patients, the Fisher exact test was used. After identification of potentially influential variables, multivariate analyses were carried out with a Cox proportional hazards regression analysis using maximum likelihood methods. The outcome variables were late mortality, intervention-free survival, and freedom from reoperation. The p value to enter variables into the model was 0.05 or less.
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Results
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Operative Mortality and Perioperative Complications
The operative mortality rate in the study group was 2.3% versus 0% in the control group (Table 4). All four deaths were due to perioperative myocardial infarction. There were significantly more patients with perioperative myocardial infarction in the study group but fewer with ventricular or atrial arrhythmia than in the control group. Sternal instability was seen more often in the control group.
Survival and Reintervention Data
The actuarial 5-year, 10-year, and 15-year survival rates were 92%, 86%, and 72% in the study group and 92%, 86%, and 66% in the control group. There were no significant differences between the two groups (p = 0.202) (Fig 1). Higher preoperative angina pectoris New York Heart Association class (p < 0.001), lower left ventricular ejection fraction (<0.45) (p = 0.001), and use of vein grafts alone without an IMA graft (p = 0.044) were significant predictors of decreased survival (Fig 2Fig 3).
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Actuarial survival of young versus older patients (p = 0.202). Actuarial survival rates at 5, 10, and 15 years were 92%, 86%, and 72%, respectively, for the young group and 92%, 86%, and 66% for the older group.
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Actuarial survival of all patients with internal mammary artery graft versus vein grafts only (p = 0.044).
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The causes of late death are shown in Table 5. No statistical analysis was done of causes of late death because too many were unknown.
Table 6 summarizes the reintervention data. Cardiac reoperation, late PTCA, and late myocardial infarction occurred significantly more often in the study group than in the control group. One death in the study group was noted after reoperation.
Univariate and Multivariate Analyses
To find the predictors of late mortality and freedom from cardiac reoperation, 25 clinical variables were tested by means of univariate analysis followed by multivariate analysis. Because so few patients died early after operation, we did not look for the predictors of operative mortality. The 25 variables analyzed were age, sex, smoking, hypertension, hypercholesterolemia, obesity, positive family history, diabetes, preoperative myocardial infarction, angina pectoris New York Heart Association class, left ventricular ejection fraction, preoperative PTCA, number of diseased vessels, left main CAD, number of bypass grafts, use of single IMA, use of bilateral IMAs, endarterectomy of a vessel, cardiopulmonary bypass time, aortic cross-clamp time, emergent operation, era of operation, perioperative myocardial infarction, support with intraaortic balloon counterpulsation, and support by catecholamines.
Predictors of Late Mortality
Of the 25 variables, six were significant (p < 0.05): preoperative unstable angina, left ventricular ejection fraction lower than 0.45, vein grafts alone without any IMA graft, longer bypass time, use of an intraaortic balloon pump, and use of catecholamines. Subsequent multivariate regression analysis revealed that only preoperative unstable angina, left ventricular ejection fraction of less than 0.45, and vein grafts alone without an IMA graft were significant independent predictors.
Predictors of Freedom from Cardiac Reoperation
Multivariate regression analysis revealed that age was the only significant independent predictor. That means that the younger patients had significantly more cardiac reoperations.
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Comment
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Comparing Long-Term Results Between Young and Old Patients
The principal aim of this study was to find out whether young patients, patients aged 40 years or less, have a different long-term outcome after CABG than older patients. For comparison, a matched control group consisting of patients who were 25 to 30 years older was used. Clinical variables such as poor left ventricular ejection fraction, known to be a predictor of decreased survival [4] [5] [6], may be more frequent in one group and may be responsible for a worse outcome. We have attempted to isolate the variable age by matching young patients with older patients (25 to 30 years older) having the same left ventricular ejection fraction, sex, year of operation, and number of bypass grafts.
There were no significant differences between the study group and the control group in terms of long-term survival despite the fact that 15 years after CABG, the control group with a mean age of 64.2 years at operation had almost reached a mean age of 80 years (see Fig 1). Coronary angiography in the follow-up was performed in 77 patients in the young group and 47 patients in the older group. Progression of CAD was more frequent and more impressive in the young group. The reintervention rate (cardiac reoperation and PTCA) was more than three times higher in the study group than in the control group, and there were more late myocardial infarctions in the study group (see Table 6). We were able to demonstrate that use of the IMA as a bypass graft significantly increased survival in all our patients (see Fig 3). Sixty-eight percent of our young patients returned to work, which is comparable to the findings in other reports [7] [8] [9]. The patient’s own perception of the disease and the prognosis seems to be at least as important as the success of revascularization in determining employment after CABG [9] [10].
Some reports [2] [3] of CABG in young patients show disappointing results for operative mortality, symptomatic relief, and long-term survival. Early-onset CAD may be an indicator of rapidly progressing atherosclerosis [11] [12] [13] [14] [15]. Cohen and associates [2] compared patients less than 36 years of age who had operation between 1970 and 1980 with two matched control groups of middle-aged and elderly patients. There was a significantly worse 8-year event-free survival in the young group (27%) versus the middle-aged group (61%) and the elderly group (59%). In a retrospective study, Kelly and co-workers [3] compared patients less than 40 years old operated on between 1968 and 1984 with a group of patients previously studied at the same hospital. This control group included all patients having CABG and was not matched. It was therefore difficult to show an influence of age on outcome. The authors found the reoperation rate was 14 times higher in the younger patients than in the older patients (16.2% versus 1.2%).
Kelly and colleagues [7] showed a worse rate of vein graft patency in patients 40 years old or less compared with the average patient population, and Lytle and Loop [11] found a 93% patency rate for IMA grafts in a series of young patients compared with a 56% patency rate for saphenous vein grafts. In addition, the patency rate of saphenous vein grafts in young adults was inferior to vein graft patency in older patients. Data from the Montreal Heart Institute [16] indicated that stenoses occurring in vein grafts 7 to 12 years after operation are related to hypercholesterolemia, whereas stenoses occurring earlier are related to technical problems during operation and not to cardiac risk factors.
Reasons for the higher intervention rate in young patients are probably, on the one hand, the increased presence of coronary risk factors such as hyperlipidemia, smoking, and a family history of CAD resulting in a higher incidence of early graft occlusion [8] [17]. On the other hand, the frequent use of saphenous veins grafts in these young patients could explain the higher rate of reintervention and late myocardial infarction. The increasing use of the IMA as a graft since the early 1980s with its proven superior long-term patency compared with the saphenous vein graft [18] [19] [20] and the established use of PTCA have provided some cause for optimism in the treatment of young patients. Twenty-four percent of our young patients had one-vessel disease, and nowadays they would probably be treated with PTCA.
Coronary Risk Factors in the Two Groups and Their Influence on Mortality and Morbidity
There were many differences in cardiac risk factors between the two groups. Smoking and hypercholesterolemia were significantly more frequent in young patients, and diabetes and hypertension were significantly more frequent in the older patients. Other studies [2] [3] [12] have found a similar prevalence and proportion of cardiac risk. In our report, cardiac risk factors had no influence on long-term survival. As already mentioned, vein graft failure seems to be associated with hypercholesterolemia [16], a cardiac risk factor significantly correlated with young patients. In univariate and multivariate analyses, cardiac risk factors were not predictors of mortality and morbidity but were strongly correlated with the age of the patients.
Variables Significantly Affecting Survival in Young and Old Patients
In our study, preoperative unstable angina, left ventricular ejection fraction less than 0.45, and use of vein grafts alone without an IMA graft were predictors of decreased survival. In a study of young patients by Zehr and co-workers [9], diabetes and left main disease were predictors of decreased survival and diabetes and era of operation were predictors of decreased intervention-free survival. A high number of diseased vessels and poor left ventricular function were predictors of decreased survival as demonstrated by Khan and colleagues [4]. Increased survival in patients with IMA grafts was found by Cameron and coauthors [21]. Compared with vein grafts alone, IMA grafts resulted in an increase in survival of 4.4 years in all age groups. In addition, IMA grafts were associated with fewer reoperations, fewer late myocardial infarctions, lower associated mortality rates, and later recurrence of angina and remained more resistant to atherosclerosis for a long period. Other studies [18] [19] [20] have reported superior clinical results with IMA grafts at 7, 10, and 15 years. We agree with Lytle and Loop [11] in recommending IMA grafting, including bilateral IMA grafts, especially in young patients, who often have rapidly progressive vein graft disease. The IMA graft should influence the reoperation rate positively.
Conclusions
This retrospective study shows that there is little difference in long-term survival after CABG between young and old patients. However the reintervention rate (cardiac reoperation or subsequent PTCA) is higher in the younger group. Absence of unstable angina, left ventricular ejection fraction greater than 0.45, and use of IMA grafts increase survival in all patients.
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Acknowledgments
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We thank Matthias Meier, dipl. math ETH Zürich, consultant statistician.
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References
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Abstract
Introduction
