- Email: [email protected]
The Impact of Peripheral Vascular Disease on Long-Term Survival After Coronary Artery Bypass Graft Surgery
Danny Chu, MD, Faisal G. Bakaeen, MD, Xing Li Wang, MD, PhD, Tam K. Dao, PhD, Scott A. LeMaire, MD, Joseph S. Coselli, MD, and Joseph Huh, MD Division of Cardiothoracic Surgery and Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Division of Cardiothoracic Surgery, Michael E. DeBakey Veterans Affairs Medical Center, and Section of Adult Cardiac Surgery, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas
Background. Although peripheral vascular disease is known to negatively affect overall survival, its effects on survival after surgical myocardial revascularization have not been well described. The objective of this study was to examine the impact of peripheral vascular disease on long-term survival after coronary artery bypass grafting. 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% ⴞ 4.1% versus 82.8% ⴞ 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p ⴝ 0.004). Conclusions. Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor longterm 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.
P
ies 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 inhospital 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.
eripheral vascular disease (PVD) adversely affects overall long-term survival in the general population [1-3]. The mortality risk associated with PVD is as high as threefold, as described by Criqui and colleagues [1]. Furthermore, studies have shown that patients with PVD have a high prevalence of coronary artery disease (CAD) [4-6]. Coronary artery bypass graft (CABG) operations are a well-established and proven method of treating multivessel CAD [7]. However, numerous studies have demonstrated adverse short-term outcomes among patients with PVD who undergo CABG [8-12]. Specifically, subgroup analyses of large series of CABG operations have shown that the presence of PVD increases operative mortality rates 1.6- to 2.9-fold [13-15]. 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 stud-
(Ann Thorac Surg 2008;86:1175– 80) © 2008 by The Society of Thoracic Surgeons
Material and Methods 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; e-mail: [email protected].
© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Patients The study was granted waiver of consent and approved by the Institutional Review Board at Michael E. DeBakey 0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.06.024
ADULT CARDIAC
The Impact of Peripheral Vascular Disease on Long-Term Survival After Coronary Artery Bypass Graft Surgery
1176
ADULT CARDIAC
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas. Data were obtained from the medical center’s Continuous Improvement in Cardiac Surgery Program (CICSP) database. This database, organized by the Department of Veterans Affairs (VA) to provide continuous assessment and improvement of quality of care for all patients undergoing cardiac surgery in VA hospitals, contains comprehensive data (on more than 140 variables, including demographic, clinical, outcome, and resource variables) collected prospectively at prespecified time points from all patients undergoing cardiac surgical procedures in the VA health care system [18]. Data in the CICSP database were collected by a research nurse through reviews of each patient’s computerized medical record. 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
Table 1. Preoperative Patient Characteristics Patients Without PVD (n ⫽ 794)
Patients With PVD (n ⫽ 370)
p Value
61.0 ⫾ 8.2 788 (99.2) 91.8 ⫾ 18.5 1.8 ⫾ 0.1 2.1 ⫾ 0.2 3.7 ⫾ 0.4 1.2 ⫾ 0.6 372 (34.3) 126 (15.9) 310 (39.0) 528 (66.5) 271 (34.1) 473 (59.6) 6 (0.8)
63.2 ⫾ 8.6 372 (99.5) 89.9 ⫾ 17.5 1.8 ⫾ 0.1 2.0 ⫾ 0.2 3.6 ⫾ 0.4 1.2 ⫾ 0.5 151 (40.8) 125 (33.8) 160 (43.2) 289 (78.1) 148 (40.0) 293 (79.2) 2 (0.5)
⬍ 0.0001 0.67 0.09 0.31 0.29 0.002 0.33 0.04 ⬍ 0.0001 0.17 ⬍ 0.0001 0.05 ⬍ 0.0001 0.68
Age (years) Male sex, n (%) Body weight (kg) Height (m) Body surface area (m2) Preoperative albumin level (g/dL) Preoperative creatinine level (mg/dL) Current tobacco smoker, n (%) Cerebral vascular disease, n (%) Diabetes mellitus, n (%) CCS angina class III–IV, n (%) NYHA heart failure class III–IV, n (%) Prior myocardial infarction, n (%) Previous PCI (⬍ 3 days), n (%) Data are presented as mean ⫾ SD or as number (percentage). CCS ⫽ Canadian Cardiovascular Society; peripheral vascular disease.
NYHA ⫽ New York Heart Association;
PCI ⫽ percutaneous coronary intervention;
PVD ⫽
Ann Thorac Surg 2008;86:1175– 80
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
1177
Patients Without PVD (n ⫽ 794)
Patients With PVD (n ⫽ 370)
p Value
113.9 ⫾ 34.4 64.2 ⫾ 20.4 2.0 ⫾ 0.8 0.9 ⫾ 0.3 9 (1.1) 15 (1.9) 9 (1.1) 9 (1.1) 51 (6.4) 13 (1.6) 5 (0.6) 3 (0.4)
112.8 ⫾ 39.6 61.6 ⫾ 27.8 1.9 ⫾ 0.8 0.9 ⫾ 0.3 8 (2.2) 8 (2.2) 4 (1.1) 7 (1.9) 32 (8.6) 11 (3.0) 1 (0.3) 3 (0.8)
0.61 0.07 0.16 0.51 0.19 0.76 1.0 0.29 0.18 0.14 0.43 0.34
Cardiopulmonary bypass time (min) Aortic cross-clamp time (min) Vein grafts, number per patient IMA grafts, number per patient Renal failure (dialysis), n (%) Stroke, n (%) Reexploration for bleeding, n (%) Mediastinitis, n (%) On ventilator ⬎ 48 hours, n (%) Cardiac arrest, n (%) New mechanical circulatory support, n (%) Perioperative myocardial infarction, n (%) Data are presented as mean ⫾ SD or number (percentages). CPB ⫽ cardiopulmonary bypass;
IMA ⫽ internal mammary artery;
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
PVD ⫽ peripheral vascular disease.
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.
Table 3. Univariate and Multivariate Logistic Regression Analysis of Variables Associated With All-Cause 30-Day Mortality Univariate Analysis
Age Weight Height Body surface area Albumin level Creatinine level Current tobacco smoker Cerebral vascular disease Diabetes mellitus CCS angina class III–IV NYHA heart failure class III–IV Prior myocardial infarction Cardiopulmonary bypass time Aortic cross-clamp time Number of vein grafts Number of IMA grafts Without PVD With PVD CCS ⫽ Canadian Cardiovascular Society; PVD ⫽ peripheral vascular disease.
Multivariate Analysis
Odds Ratio (95% CI)
p Value
Odds Ratio (95% CI)
p Value
1.15 (1.08–1.23) 1.00 (0.99–1.01) 1.00 (0.89–1.11) 0.74 (0.10–5.64) 0.52 (0.21–1.32) 1.42 (1.02–1.98) 1.05 (0.38–2.92) 1.22 (0.39–3.80) 0.49 (0.16–1.52) 1.85 (0.55–6.55) 1.39 (0.51–3.76) 1.57 (0.50–4.91) 1.01 (1.00–1.02) 1.00 (0.98–1.02) 0.85 (0.47–1.55) 0.46 (0.14–1.56) Reference 2.17 (0.81–5.83)
⬍ 0.0001 0.75 0.93 0.77 0.17 0.04 0.92 0.74 0.22 0.34 0.52 0.44 0.004 0.89 0.59 0.21 Reference 0.12
1.15 (1.08–1.23) — — — — — — — — — — — — — — — Reference —
⬍ 0.0001 — — — — — — — — — — — — — — — Reference —
CI ⫽ confidence interval;
IMA ⫽ internal mammary artery;
NYHA ⫽ New York Heart Association;
ADULT CARDIAC
Table 2. Intraoperative and Postoperative Characteristics
1178
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
Table 4. Univariate and Multivariate Logistic Regression Analysis of Variables Associated With 30-Day Major Adverse Cardiac Event Univariate Analysis ADULT CARDIAC
Age Weight Height Body surface area Albumin level Creatinine level Current tobacco smoker Cerebral vascular disease Diabetes mellitus CCS angina class III–IV NYHA heart failure class III–IV Prior myocardial infarction Cardiopulmonary bypass time Aortic cross-clamp time Number of vein grafts Number of IMA grafts Without PVD With PVD CCS ⫽ Canadian Cardiovascular Society; PVD ⫽ peripheral vascular disease.
Multivariate Analysis
Odds Ratio (95% CI)
p Value
Odds Ratio (95% CI)
p Value
1.06 (1.01–1.11) 1.00 (0.99–1.01) 1.00 (0.91–1.09) 0.78 (0.16–3.75) 0.63 (0.29–1.37) 1.10 (0.65–1.88) 0.83 (0.37–1.84) 0.79 (0.30–2.10) 0.49 (0.20–1.15) 1.06 (0.46–2.44) 0.99 (0.45–2.16) 0.94 (0.43–2.05) 1.01 (1.00–1.02) 1.00 (0.98–1.02) 0.83 (0.52–1.30) 0.39 (0.16–0.95) Reference 1.89 (0.89–4.02)
0.01 0.68 0.98 0.76 0.25 0.72 0.64 0.63 0.10 0.89 0.98 0.87 0.003 0.81 0.41 0.04 Reference 0.10
1.05 (1.01–1.10) — — — — — — — — — — — 1.02 (1.01–1.03) 0.97 (0.95–0.99) — — Reference —
0.03 — — — — — — — — — — — ⬍ 0.0001 0.01 — — Reference —
CI ⫽ confidence interval;
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 crossclamp 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).
IMA ⫽ internal mammary artery;
NYHA ⫽ New York Heart Association;
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
Results For the purpose of this study, PVD 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 of 50% or more of the luminal diameter. Preoperative characteristics of the patients are shown in Table 1. With the exception of age, most demographic characteristics, including sex, weight, height, and body
Fig 1. Unadjusted Kaplan-Meier survival curves after coronary artery bypass grafting in patients with (⫹ [gray line]) and without (– [black line]) peripheral vascular disease (PVD). Numbers along the curves designate patients at risk at specific intervals.
Ann Thorac Surg 2008;86:1175– 80
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
1179
Comment
Fig 2. Risk-adjusted Cox proportional hazards regression survival curves after coronary artery bypass graft surgery in patients with (⫹ [gray line]) and without (⫺ [black line]) peripheral vascular disease (PVD). Numbers along the curves designate patients at risk at specific intervals.
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. Intraoperative and postoperative characteristics are shown in Table 2. The two groups of patients did not differ significantly in terms of intraoperative variables, including cardiopulmonary bypass time, aortic crossclamp time, number of vein grafts, and number of internal mammary artery grafts. Postoperative outcome measures, including stroke, reexploration for bleeding, mediastinitis, ventilator dependence for more than 48 hours, cardiac arrest, new mechanical circulatory support, and perioperative myocardial infarction, were also similar between the two groups of patients. The primary and secondary study endpoints are shown in Table 3, Table 4, Figure 1, and Figure 2. Table 3 shows univariate and multivariate logistic regression analysis of various predictors on 30-day mortality as an endpoint whereas Table 4 uses major adverse cardiac events as an endpoint. The presence of PVD was not identified as an independent predictor of increased rates of 30-day mortality or major adverse cardiac events by multivariate analysis (Tables 3 and 4). Unadjusted Kaplan-Meier survival curves were generated for the two groups of patients (Fig 1), and Cox proportional hazards regression analysis was used to adjust for potential preoperative and intraoperative confounding factors. The Cox proportional hazards regression survival curves (Fig 2) showed that, independent of other predictors, PVD was associated with poorer long-term survival after CABG. Specifically, the 9-year survival rate was 72.9% ⫾ 4.1% (mean ⫾ SEM) for patients with PVD and 82.8% ⫾ 2.4% for patients
We found that patients with PVD have a higher incidence of comorbidities and are generally sicker than patients without PVD. However, even after these potential confounding factors were adjusted for, the mere presence of PVD was found to be an independent predictor of poorer long-term survival after CABG: patients with PVD had nearly twice the risk of late mortality after CABG surgery than patients without PVD had. 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 longterm 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
ADULT CARDIAC
without PVD. The adjusted hazard ratio was 1.7 (95% confidence interval: 1.2 to 2.4; p ⫽ 0.004) for patients with PVD.
1180
ADULT CARDIAC
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
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.
4. Eagle KA, Rihal CS, Foster ED, Mickel MC, Gersh BJ. Long-term survival in patients with coronary artery disease: importance of peripheral vascular disease. The Coronary Artery Surgery Study (CASS) Investigators. J Am Coll Cardiol 1994;23:1091–5. 5. Brandt M, Harder K, Walluscheck KP, Fraund S, Boning A, Cremer J. Coronary artery bypass surgery in diabetic patients. J Card Surg 2004;19:36 – 40. 6. Hertzer NR, Beven EG, Young JR, et al. Coronary artery disease in peripheral vascular patients: a classification of 1000 coronary angiograms and results of surgical management. Ann Surg 1984;199:223–33. 7. Niles NW, McGrath PD, Malenka D, et al. Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study. Northern New England Cardiovascular Disease Study Group. J Am Coll Cardiol 2001;37:1008 –15. 8. Gersh BJ, Califf RM, Loop FD, Akins CW, Pryor DB, Takaro TC. Coronary bypass surgery in chronic stable angina. Circulation 1989;79:I46 –59. 9. Kunadian B, Dunning J, Millner RW. Modifiable risk factors remain significant causes of medium term mortality after first time coronary artery bypass grafting. J Cardiothorac Surg 2007;2:51. 10. Magovern JA, Sakert T, Magovern GJ, et al. A model that predicts morbidity and mortality after coronary artery bypass graft surgery. J Am Coll Cardiol 1996;28:1147–53. 11. Rosenthal GE, Vaughan Sarrazin M, Hannan EL. In-hospital mortality following coronary artery bypass graft surgery in Veterans Health Administration and private sector hospitals. Med Care 2003;41:522–35. 12. Sutton-Tyrrell K, Rihal C, Sellers MA, et al. Long-term prognostic value of clinically evident noncoronary vascular disease in patients undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI). Am J Cardiol 1998;81:375– 81. 13. Grover FL, Hammermeister KE, Burchfiel C. Initial report of the Veterans Administration Preoperative Risk Assessment Study for Cardiac Surgery. Ann Thorac Surg 1990;50:12–26. 14. Higgins TL, Estafanous FG, Loop FD, Beck GJ, Blum JM, Paranandi L. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients: a clinical severity score. JAMA 1992;267:2344 – 8. 15. O’Connor GT, Plume SK, Olmstead EM, et al. Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group. Circulation 1992;85: 2110 – 8. 16. Birkmeyer JD, Quinton HB, O’Connor NJ, et al. The effect of peripheral vascular disease on long-term mortality after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. Arch Surg 1996;131:316 –21. 17. Birkmeyer JD, O’Connor GT, Quinton HB, et al. The effect of peripheral vascular disease on in-hospital mortality rates with coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. J Vasc Surg 1995;21: 445–52. 18. Hammermeister KE, Johnson R, Marshall G, Grover FL. Continuous assessment and improvement in quality of care: a model from the Department of Veterans Affairs cardiac surgery. Ann Surg 1994;219:281–90. 19. Shub C, Vlietstra RE, Smith HC, Fulton RE, Elveback LR. The unpredictable progression of symptomatic coronary artery disease: a serial clinical-angiographic analysis. Mayo Clin Proc 1981;56:155– 60.
We thank Steve Palmer, PhD, ELS, for his editorial assistance in preparing this manuscript.
References 1. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381– 6. 2. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc 1985;33:13– 8. 3. Smith GD, Shipley MJ, Rose G. Intermittent claudication, heart disease risk factors, and mortality: the Whitehall Study. Circulation 1990;82:1925–31.
Background. Although peripheral vascular disease is known to negatively affect overall survival, its effects on survival after surgical myocardial revascularization have not been well described. The objective of this study was to examine the impact of peripheral vascular disease on long-term survival after coronary artery bypass grafting. 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% ⴞ 4.1% versus 82.8% ⴞ 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p ⴝ 0.004). Conclusions. Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor longterm 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.
P
ies 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 inhospital 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.
eripheral vascular disease (PVD) adversely affects overall long-term survival in the general population [1-3]. The mortality risk associated with PVD is as high as threefold, as described by Criqui and colleagues [1]. Furthermore, studies have shown that patients with PVD have a high prevalence of coronary artery disease (CAD) [4-6]. Coronary artery bypass graft (CABG) operations are a well-established and proven method of treating multivessel CAD [7]. However, numerous studies have demonstrated adverse short-term outcomes among patients with PVD who undergo CABG [8-12]. Specifically, subgroup analyses of large series of CABG operations have shown that the presence of PVD increases operative mortality rates 1.6- to 2.9-fold [13-15]. 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 stud-
(Ann Thorac Surg 2008;86:1175– 80) © 2008 by The Society of Thoracic Surgeons
Material and Methods 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; e-mail: [email protected].
© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Patients The study was granted waiver of consent and approved by the Institutional Review Board at Michael E. DeBakey 0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.06.024
ADULT CARDIAC
The Impact of Peripheral Vascular Disease on Long-Term Survival After Coronary Artery Bypass Graft Surgery
1176
ADULT CARDIAC
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas. Data were obtained from the medical center’s Continuous Improvement in Cardiac Surgery Program (CICSP) database. This database, organized by the Department of Veterans Affairs (VA) to provide continuous assessment and improvement of quality of care for all patients undergoing cardiac surgery in VA hospitals, contains comprehensive data (on more than 140 variables, including demographic, clinical, outcome, and resource variables) collected prospectively at prespecified time points from all patients undergoing cardiac surgical procedures in the VA health care system [18]. Data in the CICSP database were collected by a research nurse through reviews of each patient’s computerized medical record. 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
Table 1. Preoperative Patient Characteristics Patients Without PVD (n ⫽ 794)
Patients With PVD (n ⫽ 370)
p Value
61.0 ⫾ 8.2 788 (99.2) 91.8 ⫾ 18.5 1.8 ⫾ 0.1 2.1 ⫾ 0.2 3.7 ⫾ 0.4 1.2 ⫾ 0.6 372 (34.3) 126 (15.9) 310 (39.0) 528 (66.5) 271 (34.1) 473 (59.6) 6 (0.8)
63.2 ⫾ 8.6 372 (99.5) 89.9 ⫾ 17.5 1.8 ⫾ 0.1 2.0 ⫾ 0.2 3.6 ⫾ 0.4 1.2 ⫾ 0.5 151 (40.8) 125 (33.8) 160 (43.2) 289 (78.1) 148 (40.0) 293 (79.2) 2 (0.5)
⬍ 0.0001 0.67 0.09 0.31 0.29 0.002 0.33 0.04 ⬍ 0.0001 0.17 ⬍ 0.0001 0.05 ⬍ 0.0001 0.68
Age (years) Male sex, n (%) Body weight (kg) Height (m) Body surface area (m2) Preoperative albumin level (g/dL) Preoperative creatinine level (mg/dL) Current tobacco smoker, n (%) Cerebral vascular disease, n (%) Diabetes mellitus, n (%) CCS angina class III–IV, n (%) NYHA heart failure class III–IV, n (%) Prior myocardial infarction, n (%) Previous PCI (⬍ 3 days), n (%) Data are presented as mean ⫾ SD or as number (percentage). CCS ⫽ Canadian Cardiovascular Society; peripheral vascular disease.
NYHA ⫽ New York Heart Association;
PCI ⫽ percutaneous coronary intervention;
PVD ⫽
Ann Thorac Surg 2008;86:1175– 80
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
1177
Patients Without PVD (n ⫽ 794)
Patients With PVD (n ⫽ 370)
p Value
113.9 ⫾ 34.4 64.2 ⫾ 20.4 2.0 ⫾ 0.8 0.9 ⫾ 0.3 9 (1.1) 15 (1.9) 9 (1.1) 9 (1.1) 51 (6.4) 13 (1.6) 5 (0.6) 3 (0.4)
112.8 ⫾ 39.6 61.6 ⫾ 27.8 1.9 ⫾ 0.8 0.9 ⫾ 0.3 8 (2.2) 8 (2.2) 4 (1.1) 7 (1.9) 32 (8.6) 11 (3.0) 1 (0.3) 3 (0.8)
0.61 0.07 0.16 0.51 0.19 0.76 1.0 0.29 0.18 0.14 0.43 0.34
Cardiopulmonary bypass time (min) Aortic cross-clamp time (min) Vein grafts, number per patient IMA grafts, number per patient Renal failure (dialysis), n (%) Stroke, n (%) Reexploration for bleeding, n (%) Mediastinitis, n (%) On ventilator ⬎ 48 hours, n (%) Cardiac arrest, n (%) New mechanical circulatory support, n (%) Perioperative myocardial infarction, n (%) Data are presented as mean ⫾ SD or number (percentages). CPB ⫽ cardiopulmonary bypass;
IMA ⫽ internal mammary artery;
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
PVD ⫽ peripheral vascular disease.
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.
Table 3. Univariate and Multivariate Logistic Regression Analysis of Variables Associated With All-Cause 30-Day Mortality Univariate Analysis
Age Weight Height Body surface area Albumin level Creatinine level Current tobacco smoker Cerebral vascular disease Diabetes mellitus CCS angina class III–IV NYHA heart failure class III–IV Prior myocardial infarction Cardiopulmonary bypass time Aortic cross-clamp time Number of vein grafts Number of IMA grafts Without PVD With PVD CCS ⫽ Canadian Cardiovascular Society; PVD ⫽ peripheral vascular disease.
Multivariate Analysis
Odds Ratio (95% CI)
p Value
Odds Ratio (95% CI)
p Value
1.15 (1.08–1.23) 1.00 (0.99–1.01) 1.00 (0.89–1.11) 0.74 (0.10–5.64) 0.52 (0.21–1.32) 1.42 (1.02–1.98) 1.05 (0.38–2.92) 1.22 (0.39–3.80) 0.49 (0.16–1.52) 1.85 (0.55–6.55) 1.39 (0.51–3.76) 1.57 (0.50–4.91) 1.01 (1.00–1.02) 1.00 (0.98–1.02) 0.85 (0.47–1.55) 0.46 (0.14–1.56) Reference 2.17 (0.81–5.83)
⬍ 0.0001 0.75 0.93 0.77 0.17 0.04 0.92 0.74 0.22 0.34 0.52 0.44 0.004 0.89 0.59 0.21 Reference 0.12
1.15 (1.08–1.23) — — — — — — — — — — — — — — — Reference —
⬍ 0.0001 — — — — — — — — — — — — — — — Reference —
CI ⫽ confidence interval;
IMA ⫽ internal mammary artery;
NYHA ⫽ New York Heart Association;
ADULT CARDIAC
Table 2. Intraoperative and Postoperative Characteristics
1178
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
Table 4. Univariate and Multivariate Logistic Regression Analysis of Variables Associated With 30-Day Major Adverse Cardiac Event Univariate Analysis ADULT CARDIAC
Age Weight Height Body surface area Albumin level Creatinine level Current tobacco smoker Cerebral vascular disease Diabetes mellitus CCS angina class III–IV NYHA heart failure class III–IV Prior myocardial infarction Cardiopulmonary bypass time Aortic cross-clamp time Number of vein grafts Number of IMA grafts Without PVD With PVD CCS ⫽ Canadian Cardiovascular Society; PVD ⫽ peripheral vascular disease.
Multivariate Analysis
Odds Ratio (95% CI)
p Value
Odds Ratio (95% CI)
p Value
1.06 (1.01–1.11) 1.00 (0.99–1.01) 1.00 (0.91–1.09) 0.78 (0.16–3.75) 0.63 (0.29–1.37) 1.10 (0.65–1.88) 0.83 (0.37–1.84) 0.79 (0.30–2.10) 0.49 (0.20–1.15) 1.06 (0.46–2.44) 0.99 (0.45–2.16) 0.94 (0.43–2.05) 1.01 (1.00–1.02) 1.00 (0.98–1.02) 0.83 (0.52–1.30) 0.39 (0.16–0.95) Reference 1.89 (0.89–4.02)
0.01 0.68 0.98 0.76 0.25 0.72 0.64 0.63 0.10 0.89 0.98 0.87 0.003 0.81 0.41 0.04 Reference 0.10
1.05 (1.01–1.10) — — — — — — — — — — — 1.02 (1.01–1.03) 0.97 (0.95–0.99) — — Reference —
0.03 — — — — — — — — — — — ⬍ 0.0001 0.01 — — Reference —
CI ⫽ confidence interval;
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 crossclamp 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).
IMA ⫽ internal mammary artery;
NYHA ⫽ New York Heart Association;
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
Results For the purpose of this study, PVD 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 of 50% or more of the luminal diameter. Preoperative characteristics of the patients are shown in Table 1. With the exception of age, most demographic characteristics, including sex, weight, height, and body
Fig 1. Unadjusted Kaplan-Meier survival curves after coronary artery bypass grafting in patients with (⫹ [gray line]) and without (– [black line]) peripheral vascular disease (PVD). Numbers along the curves designate patients at risk at specific intervals.
Ann Thorac Surg 2008;86:1175– 80
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
1179
Comment
Fig 2. Risk-adjusted Cox proportional hazards regression survival curves after coronary artery bypass graft surgery in patients with (⫹ [gray line]) and without (⫺ [black line]) peripheral vascular disease (PVD). Numbers along the curves designate patients at risk at specific intervals.
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. Intraoperative and postoperative characteristics are shown in Table 2. The two groups of patients did not differ significantly in terms of intraoperative variables, including cardiopulmonary bypass time, aortic crossclamp time, number of vein grafts, and number of internal mammary artery grafts. Postoperative outcome measures, including stroke, reexploration for bleeding, mediastinitis, ventilator dependence for more than 48 hours, cardiac arrest, new mechanical circulatory support, and perioperative myocardial infarction, were also similar between the two groups of patients. The primary and secondary study endpoints are shown in Table 3, Table 4, Figure 1, and Figure 2. Table 3 shows univariate and multivariate logistic regression analysis of various predictors on 30-day mortality as an endpoint whereas Table 4 uses major adverse cardiac events as an endpoint. The presence of PVD was not identified as an independent predictor of increased rates of 30-day mortality or major adverse cardiac events by multivariate analysis (Tables 3 and 4). Unadjusted Kaplan-Meier survival curves were generated for the two groups of patients (Fig 1), and Cox proportional hazards regression analysis was used to adjust for potential preoperative and intraoperative confounding factors. The Cox proportional hazards regression survival curves (Fig 2) showed that, independent of other predictors, PVD was associated with poorer long-term survival after CABG. Specifically, the 9-year survival rate was 72.9% ⫾ 4.1% (mean ⫾ SEM) for patients with PVD and 82.8% ⫾ 2.4% for patients
We found that patients with PVD have a higher incidence of comorbidities and are generally sicker than patients without PVD. However, even after these potential confounding factors were adjusted for, the mere presence of PVD was found to be an independent predictor of poorer long-term survival after CABG: patients with PVD had nearly twice the risk of late mortality after CABG surgery than patients without PVD had. 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 longterm 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
ADULT CARDIAC
without PVD. The adjusted hazard ratio was 1.7 (95% confidence interval: 1.2 to 2.4; p ⫽ 0.004) for patients with PVD.
1180
ADULT CARDIAC
CHU ET AL SURVIVAL AFTER CORONARY ARTERY BYPASS SURGERY
Ann Thorac Surg 2008;86:1175– 80
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.
4. Eagle KA, Rihal CS, Foster ED, Mickel MC, Gersh BJ. Long-term survival in patients with coronary artery disease: importance of peripheral vascular disease. The Coronary Artery Surgery Study (CASS) Investigators. J Am Coll Cardiol 1994;23:1091–5. 5. Brandt M, Harder K, Walluscheck KP, Fraund S, Boning A, Cremer J. Coronary artery bypass surgery in diabetic patients. J Card Surg 2004;19:36 – 40. 6. Hertzer NR, Beven EG, Young JR, et al. Coronary artery disease in peripheral vascular patients: a classification of 1000 coronary angiograms and results of surgical management. Ann Surg 1984;199:223–33. 7. Niles NW, McGrath PD, Malenka D, et al. Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study. Northern New England Cardiovascular Disease Study Group. J Am Coll Cardiol 2001;37:1008 –15. 8. Gersh BJ, Califf RM, Loop FD, Akins CW, Pryor DB, Takaro TC. Coronary bypass surgery in chronic stable angina. Circulation 1989;79:I46 –59. 9. Kunadian B, Dunning J, Millner RW. Modifiable risk factors remain significant causes of medium term mortality after first time coronary artery bypass grafting. J Cardiothorac Surg 2007;2:51. 10. Magovern JA, Sakert T, Magovern GJ, et al. A model that predicts morbidity and mortality after coronary artery bypass graft surgery. J Am Coll Cardiol 1996;28:1147–53. 11. Rosenthal GE, Vaughan Sarrazin M, Hannan EL. In-hospital mortality following coronary artery bypass graft surgery in Veterans Health Administration and private sector hospitals. Med Care 2003;41:522–35. 12. Sutton-Tyrrell K, Rihal C, Sellers MA, et al. Long-term prognostic value of clinically evident noncoronary vascular disease in patients undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI). Am J Cardiol 1998;81:375– 81. 13. Grover FL, Hammermeister KE, Burchfiel C. Initial report of the Veterans Administration Preoperative Risk Assessment Study for Cardiac Surgery. Ann Thorac Surg 1990;50:12–26. 14. Higgins TL, Estafanous FG, Loop FD, Beck GJ, Blum JM, Paranandi L. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients: a clinical severity score. JAMA 1992;267:2344 – 8. 15. O’Connor GT, Plume SK, Olmstead EM, et al. Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group. Circulation 1992;85: 2110 – 8. 16. Birkmeyer JD, Quinton HB, O’Connor NJ, et al. The effect of peripheral vascular disease on long-term mortality after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. Arch Surg 1996;131:316 –21. 17. Birkmeyer JD, O’Connor GT, Quinton HB, et al. The effect of peripheral vascular disease on in-hospital mortality rates with coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. J Vasc Surg 1995;21: 445–52. 18. Hammermeister KE, Johnson R, Marshall G, Grover FL. Continuous assessment and improvement in quality of care: a model from the Department of Veterans Affairs cardiac surgery. Ann Surg 1994;219:281–90. 19. Shub C, Vlietstra RE, Smith HC, Fulton RE, Elveback LR. The unpredictable progression of symptomatic coronary artery disease: a serial clinical-angiographic analysis. Mayo Clin Proc 1981;56:155– 60.
We thank Steve Palmer, PhD, ELS, for his editorial assistance in preparing this manuscript.
References 1. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381– 6. 2. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc 1985;33:13– 8. 3. Smith GD, Shipley MJ, Rose G. Intermittent claudication, heart disease risk factors, and mortality: the Whitehall Study. Circulation 1990;82:1925–31.