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a Division of Cardiothoracic Surgery, Baylor College of Medicine, Houston, Texas
b Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
c Division of Cardiothoracic Surgery, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
d Section of Adult Cardiac Surgery, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas
Accepted for publication June 2, 2008.
* Address correspondence to Dr Chu, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd, OCL 112, Houston, TX 77030 (Email: dchumd{at}gmail.com).
| Abstract |
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Methods: We reviewed records of 1,164 consecutive patients (370 with peripheral vascular disease and 794 without it) who underwent primary isolated coronary artery bypass graft surgery between 1997 and 2007. Univariate and multivariate logistic regression methods were used to analyze variables associated with early outcomes. We assessed long-term survival by using Kaplan-Meier curves generated by log-rank tests, adjusting for confounding factors with Cox proportional hazards regression analysis.
Results: Patients with peripheral vascular disease were generally sicker and had more comorbidities than patients without peripheral vascular disease. The presence of peripheral vascular disease does not predict increased rates of 30-day mortality or major adverse cardiac events. However, after controlling for potential confounding factors, patients with peripheral vascular disease had a significantly worse 9-year survival rate than patients without peripheral vascular disease (72.9% ± 4.1% versus 82.8% ± 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p = 0.004).
Conclusions: Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor long-term survival among patients undergoing coronary artery bypass graft surgery. Identifying the mechanism that underlies this difference is important for improving survival in patients with peripheral vascular disease who undergo surgical myocardial revascularization.
| Introduction |
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Although the association between PVD and poor CABG short-term outcome has been established, the impact of PVD on long-term outcomes in CABG patients has not been well described. Furthermore, previous studies have not addressed potential confounding risk factors such as age, associated comorbidities, and more advanced heart disease. Noncontemporaneous series from the Northern New England Cardiovascular Disease Study Group with study patients from 2 decades ago have shown that PVD is an independent predictor of increased in-hospital mortality among CABG patients [16, 17]. As advances in preventive and critical care medicine continue to be made, it is conceivable that the prognosis of patients with PVD undergoing CABG has improved to equal that of patients without PVD in the current era.
To examine the impact of PVD on long-term survival in patients undergoing CABG in the current era of advanced medical technology, we analyzed records of patients who underwent primary isolated CABG in our institution between 1997 and 2007.
| Material and Methods |
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The death index component of the CICSP database was obtained from the Beneficiary Identification Records Locator Subsystem death file. This death file is a Veterans Benefits Administration database containing records of all beneficiaries, including veterans whose survivors applied for death benefits. In addition to these applications for VA benefits, sources of data include veterans discharged from the military service since March 1973, Medal of Honor recipients, and service members with accounts for VA education benefits. The Beneficiary Identification Records Locator Subsystem death file contains information on veterans known to be deceased. The file can be linked to other files by the veteran's real or scrambled social security number. A weekly match process with the Social Security Administration Death Master File or a notification from a hospital, cemetery, or relative/acquaintance identifies a veteran's death to be added to the file. Each January, starting in 2004, this file is refreshed with a baseline file from the Veterans Benefits Administration to ensure data accuracy by removal of records that may have populated the file inadvertently.
From the CICSP database, we identified 1,164 consecutive patients who underwent primary isolated CABG at the Michael E. DeBakey Veterans Affairs Medical Center between October 1, 1997, and March 31, 2007. We excluded patients who underwent CABG without cardiopulmonary bypass, patients who underwent CABG concomitantly with other cardiac surgical procedures, and patients with prior heart operations.
Data analyzed for each patient included age, sex, number of vein bypass grafts, number of internal mammary artery bypass grafts, cardiopulmonary bypass time, aortic cross-clamp time, current tobacco smoking status, history of cerebral vascular disease, history of diabetes mellitus, New York Heart Association (NYHA) heart failure functional class, Canadian Cardiovascular Society (CCS) angina functional class, height, weight, body surface area, preoperative albumin levels, preoperative creatinine levels, prior percutaneous coronary intervention, prior myocardial infarction, and history of PVD. Peripheral vascular disease was defined as disease of the leg arteries below the bifurcation of the aorta that was associated with one or more of the following characteristics: exertional claudication, ischemic rest pain, prior revascularization procedures on vessels to the legs, absent or diminished pulses in legs, and angiographic evidence of noniatrogenic peripheral arterial obstruction greater than or equal to 50% of luminal diameter. Patients were divided into two groups: those with PVD (n = 370) and those without PVD (n = 794).
Study Endpoints
All study endpoints used in this analysis were prespecified. The primary study endpoint was all-cause mortality. The secondary endpoint was the 30-day perioperative rate of major adverse cardiac events, which included perioperative myocardial infarction, cardiac arrest requiring cardiopulmonary resuscitation, and the need for new mechanical circulatory support. Perioperative myocardial infarction is considered to have occurred if one of the following diagnostic criteria was met: evolutionary ST-segment elevations, development of new Q waves in two or more contiguous electrocardiographic leads, and new left bundle branch block pattern on the electrocardiogram. New mechanical circulatory support was defined as the use of an intra-aortic balloon counterpulsation pump, extracorporeal membrane oxygenation, ventricular assist devices, or any combination of these.
Statistical Analysis
Descriptive statistics were summarized for categorical variables as frequencies (percentages) and compared between groups by using Pearson's
2 test or Fisher's exact test. Continuous variables, expressed as mean ± SD, were compared between groups by using the Student's t test after the data were confirmed to be normally distributed. Univariate analysis was conducted followed by multivariate stepwise logistic regression analysis. The goal of conducting univariate analysis was to allow for examination of the unique effect of each variable on our endpoints. To further assess whether these variables are independently predictive of the endpoints, multivariate stepwise logistic regression analyses were conducted where the p value of 0.05 was required to enter a variable in the model and the p value of 0.10 was required to retain the variable in the model once it has been entered. Kaplan-Meier survival curves were generated, and a log-rank test was performed to find statistical differences.
Cox proportional hazards regression analysis was then used to examine the independent effects of PVD as an independent predictor of long-term survival by controlling other confounding covariates in the forward stepwise regression model. Potential confounding covariates included in the model were age, sex, number of vein bypass grafts, number of internal mammary artery bypass grafts, cardiopulmonary bypass time, aortic cross-clamp time, current tobacco smoking status, history of cerebral vascular disease, history of diabetes mellitus, NYHA heart failure functional class, CCS angina functional class, height, weight, body surface area, preoperative albumin levels, preoperative creatinine levels, prior percutaneous coronary intervention, and prior myocardial infarction. All statistical analyses were performed with SPSS v15.0 software (SPSS, Chicago, Illinois).
| Results |
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Preoperative characteristics of the patients are shown in Table 1. With the exception of age, most demographic characteristics, including sex, weight, height, and body surface area, were not significantly different between the two groups of patients. Patients with PVD were slightly older than patients without PVD (63.2 ± 8.6 versus 61.0 ± 8.2 years; p < 0.0001). Patients with PVD had more comorbidities, including cerebral vascular disease and diabetes, than patients without PVD. Additionally, greater percentages of patients with PVD were in CCS angina functional class III or IV and in NYHA heart failure class III or IV. Preoperative serum albumin levels were slightly lower in patients with PVD than in patients without PVD. More patients with PVD were current tobacco smokers and had prior myocardial infarction.
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| Comment |
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Other studies have shown poor prognosis for CABG patients with PVD [8-12]. Gersh and colleagues [8] associated PVD with a 10% to 20% decrease in survival in after CABG. However, the authors did not adjust for potential confounding factors. Eagle and colleagues [4] were also able to show that PVD was an independent risk factor for mortality for patients with coronary artery disease. However, in that study, not all patients underwent myocardial revascularization. Although the Northern New England Cardiovascular Disease Study Group was able to show an independent, deleterious effect of PVD on outcomes in CABG patients [16, 17], these results included patients who were operated on more than 2 decades ago and are noncontemporaneous.
In the current study, we found that the presence of PVD itself is an independent predictor of poorer long-term survival for patients undergoing CABG, even in the present era of advanced medical technology and preventive care medicine. This finding suggests that there may be factors other than associated comorbidities at play in reducing long-term survival in patients with PVD after CABG operations. For example, PVD may be a marker for more severe associated coronary atherosclerotic disease. Even though the two groups of patients in our study did not differ significantly in terms of number of bypass grafts they received, patients with PVD may have more significant small-vessel CAD, which is not amenable to surgical revascularization. Specifically, it is possible that CABG patients with PVD have CAD that is more diffuse or that occurs in more vessels than do CABG patients without PVD, which would contribute to the poorer long-term survival of CABG patients with PVD. Additionally, the severity of CAD tends to increase with time, but the rate of this increase varies among patients [19]. The group of CAD patients with PVD may represent a subset of individuals with a more "virulent" form of CAD that progresses much faster than CAD in patients without PVD, thus contributing to the PVD patients' increased late mortality. Another possibility is that the decreased long-term survival among PVD patients after CABG is due to increased mortality from noncardiac causes despite successful myocardial revascularization.
One of the limitations of this study is that its primary endpoint is all-cause mortality. Using cause-specific mortality instead would have allowed us to further elucidate the causal relationship between PVD and decreased long-term survival after CABG. Also, the retrospective nature of this study has intrinsic limitations. For example, two of the diagnostic criteria for PVD used in our study were diminished or absent pulses in the legs and a history of lower extremity exertional claudication. The assessment of these criteria is physician dependent. Therefore, the accurate grouping of patients into those with PVD and those without PVD was limited by the completeness of history taking and the thoroughness of each physician performing the physical examination. Furthermore, even though the power of our study was adequate to detect a significant long-term survival difference between the two groups of patients, it may not have been adequate to detect a significant difference in other low-frequency outcome measures, such as the incidences of postoperative mediastinitis, stroke, and renal failure requiring dialysis.
Although we have shown an independent association between PVD and long-term survival in patients undergoing CABG, our findings do not prove that this association is causal. The presence of PVD may be a marker of increased post-CABG mortality for reasons that are as yet unknown. Ultimately, our research group's goal is to improve long-term survival of patients undergoing CABG. To accomplish this, we plan future studies to examine cause-specific mortality among patients with and without PVD to determine whether the causes of death differ between these groups. Prospective, randomized studies may then be designed to identify the pathophysiologic basis of the decreased life expectancy of CABG patients with PVD.
In summary, our results showed that patients with PVD have similar early postoperative CABG outcomes as patients without PVD. Additionally, PVD is associated with poorer long-term survival after CABG, and this association is independent of other comorbidities. Further studies are needed to explore the mechanisms that underlie the relationship between PVD and decreased long-term survival of patients who undergo CABG.
| Acknowledgments |
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| References |
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