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Ann Thorac Surg 2003;76:S1356-S1362
© 2003 The Society of Thoracic Surgeons

Supplement: understanding disparities in cardiovascular and thoracic surgical outcomes in African-Americans

Cardiac surgery in African Americans

Charles R. Bridges, MD, ScDa,b*

a Department of Surgery, the University of Pennsylvania Health SystemPhiladelphia, PA, USA
b Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

* Address reprint requests to Dr Bridges, Department of Surgery, Hospital of the University of Pennsylvania, The Farm Journal Building, 230 W. Washington Square, 3rd Floor, Philadelphia, PA 19106, USA
e-mail: cbridges{at}pahosp.com

Presented at the symposium on Understanding Disparities in Cardiovascular and Thoracic Surgical Outcomes in African Americans, San Diego, CA, Jan 30, 2003.


   Abstract
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Introduction
 Results derived from prospective...
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Retrospective and prospective randomized studies that provide information on the influence of race on the morbidity and mortality of cardiac surgical procedures are reviewed. We intentionally focus our attention on the specific outcomes of these procedures in African Americans because African Americans have a high incidence of all-cause cardiovascular mortality and a high prevalence of a number of risk factors associated with cardiovascular mortality. Furthermore, numerous studies have confirmed that blacks, as a function of race, lack equal access to diagnostic and therapeutic invasive cardiac procedures. Here we use the terms "black" and "African American" interchangeably. In this context we interpret both terms to refer to Americans of African descent. Similarly, we use the term "white" or "Caucasian" interchangeably to refer to Americans of European descent.


   Introduction
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Cardiovascular disease is the leading cause of death in the United States for African Americans [1, 2]. In absolute terms, the death rate for cardiovascular disease in African Americans is approximately 30% higher than it is for European Americans [1]. Coronary artery disease (CAD) is the most common etiology of cardiovascular mortality [1]. Although there have been important reductions in the death rates from cardiovascular disease in the last two decades, death rates remain unacceptably high [1, 2]. Over the same time period, the incidence of cardiovascular mortality has also decreased among African Americans but to a lesser degree than for other Americans [2, 3]. Discouragingly, the discrepancies in cardiovascular mortality as a function of race have actually increased [3, 4]. Reasons for these differences are multifactorial but inadequately investigated. Clearly, a variety of risk factors for cardiovascular disease are disproportionately prevalent in the black community including diabetes, hypertension, and obesity [1].

Although blacks have a higher incidence of risk factors for cardiovascular disease and higher death rates from cardiovascular disease, they are less likely to receive appropriate medical and surgical treatment [5–33]. They are less frequently referred for cardiac catheterization [8–13, 23], percutaneous coronary intervention (PCI) [8, 9, 11–13, 17, 21–23, 25], and coronary artery bypass graft surgery (CABG) [14–16, 20–23, 25] than whites. Overwhelmingly, the evidence has established that these differences in access cannot be accounted for on the basis of disease severity [10, 11, 15, 21, 27, 28, 31], the availability of health insurance [10, 21, 24], patient preference [10, 16], or socioeconomic status [9–11, 21, 26, 30]. Most disturbing to us as health professionals is that racial bias on the part of referring physicians whether volitional or unintentional has been implicated as an important contributing factor [10]. Importantly, the racial inequity in the use of revascularization procedures has also been associated with lower long-term survival among blacks [27].

The growing racial disparity in cardiovascular death rates and the increasing awareness of discrepancies in access to health care of black patients compared with whites leads to the hypothesis that perhaps, discrepancies in death rates may be at least in part due to lack of access to lifesaving therapies, such as CABG and PCI. Apart from any scientific analysis of cause and effect, these observations should galvanize efforts to increase the availability of revascularization procedures for blacks when indicated. Furthermore, to begin to examine the degree to which these various and disparate observations may be causally linked, patients and their physicians should understand the unique risks and benefits of these procedures in black patients. However, to date, there has been relatively limited information on the influence of race on the acute and long-term outcomes of cardiac surgery. This report will review the available data regarding the results of cardiac surgical procedures in African Americans. We sought to answer the following questions:

The articles referenced were obtained through a search of the MedLine database (1966 to present), using keywords including: race; CABG; coronary revascularization; valve surgery; and subject headings to which these terms were mapped and logical combinations of these sets. Using the same database, I performed searches for investigators active in the field. Additional references were obtained through direct communication with investigators. Published reports cited in the references retrieved were also reviewed.


   Results derived from prospective randomized controlled clinical trials
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There have been no randomized clinical trials devoted primarily to the influence of race on the outcomes of cardiac surgery. However, the results of two large, randomized, controlled studies have been utilized to provide information relevant to this issue.

Coronary artery surgery study
Maynard and colleagues [34] reviewed the survival statistics of 573 black patients and compared them to 23,008 white patients enrolled in the Coronary Artery Surgery Study (CASS) registry from1974 through 1979. The overall 5-year, age- and sex-adjusted survival rate was 88% for whites and 82% for blacks, but black race was associated with poorer survival only in the medical group. Using multivariate analysis, they found that race was not a significant predictor of 5-year survival in patients treated surgically. In addition, for black patients, surgical therapy was associated with a significant improvement in survival compared with medical therapy.

More recently, Taylor and coworkers [35] analyzed data from the (CASS) registry to determine if race is an independent predictor of long-term mortality and whether initial therapy (medical vs surgical) exerted an independent effect on survival. They obtained data at least 10-years after enrollment by administering a questionnaire by mail and through a query of the National Death Index. The mean follow-up period was 12.0 years for African Americans and 12.7 years for whites with a maximum of 18 years for both groups, and was 94% complete. The study population included 571 black and 22,754 white patients. Blacks had a higher incidence of smoking, hypertension, and diabetes mellitus than whites. In contrast to the earlier study by Maynard and colleagues [34], at 16 years of follow-up, there was a significant increase in mortality for blacks treated surgically (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.19–2.23) and for those treated medically (OR = 1.34, 95% CI = 1.11–1.63) compared with whites. Interestingly, the survival of patients who did not smoke was equal independent of race, suggesting that part of the increased mortality of black patients was due to a higher prevalence of smoking. The authors also speculated that the unequal utilization of revascularization techniques during the follow-up period might also have contributed to the higher mortality for blacks.

The bypass angioplasty revascularization investigation trial
The Bypass Angioplasty Revascularization Investigation (BARI) trial randomly assigned 1829 selected patients to undergo CABG or multivessel angioplasty [36]. After 5-years of follow-up there was no significant difference in mortality as a function of treatment strategy, although at 7 years there was a significant improvement in survival for patients treated surgically [37]. However, the improvement in survival for surgically treated patients could be accounted for based on a survival advantage for the subgroup of surgically treated patents with diabetes, whereas no survival advantage could be demonstrated for nondiabetics [37, 38]. Brooks and coworkers [39] sought to identify prognostically important clinical and angiographic characteristics of patients enrolled into the BARI registry. Black patients had a higher risk profile including a higher incidence of diabetes and congestive heart failure. After adjusting for all relevant risk factors included in a multivariate analysis, black race emerged as a significant predictor of mortality (OR = 1.34, 95% CI = 1.07–2.08). However, there was no significant interaction between race and revascularization strategy. Thus, unlike the findings of the 5-year follow-up of the CASS study [34], there was no survival advantage of CABG versus PCI that was unique to black patients.


   Results derived from retrospective analyses
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Simmons and coworkers [40] reported the survival of 1233 consecutive black patients who underwent cardiac catheterization at Cook County Hospital, a large urban municipal hospital with a predominantly black population in Chicago. Of 152 patients who underwent CABG, the 3-year survival was only 82%, significantly lower than the reported survival at that time for patients as a whole. In another study Simmons and colleagues [41] reported the results of 1022 black patients who underwent cardiac catheterization at the same institution and found that a disproportionately high percentage of black patients who underwent catheterization had unobstructed coronary arteries (41%). However, those patients with CAD had relatively severe disease. Among the male patients, 7% had left main stenosis and 53% had triple vessel disease, whereas 8% of the female patients had left main stenosis and 52% had triple vessel disease [41]. These studies did not provide comparable data for white patients [40, 41].

Gray and associates [42] reviewed the records of 3113 white and 115 black patients who underwent CABG at Cedars-Sinai Medical Center from 1984 through mid-1994 with a mean follow-up period of 3.5 years. The operative mortality was 5.5% for blacks and 4.6% for whites (p = 0.48). In a Cox multivariate regression model, black race was a significant predictor of a higher long-term mortality risk (adjusted hazard ratio 2.10, p = 0.001). Higgins and coworkers [43] analyzed the results of 2282 white and 494 black patients undergoing CABG from 1990 to 1996 at Henry Ford Hospital in Detroit. The overall operative mortality was 5.5% for black patients and 2.5% for white patients (p < 0.003). However, using multivariate logistic regression, race was not a significant predictor of mortality.


   Results derived from the society of thoracic surgeons national cardiac database
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All of the previously cited studies suffer from a relative dearth of patients to address adequately the extent to which race is an independent predictor of mortality after cardiac surgery. Only the results derived from the CASS study [34, 35] are based on sufficient numbers of patients to allow for a rigorous multivariate analysis. However, this study is based on patients enrolled nearly three decades ago. Since that time, there have been dramatic advances in cardiac surgical technology and dramatic improvements in results. As a result, two groups of investigators recently utilized The Society of Thoracic Surgeons (STS) National Cardiac Surgery Database (NCD) to evaluate the effect of race on CABG mortality. The STS NCD retrieves data from 47 states (Idaho, Vermont, and Maine are not represented), and 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, New Brunswick, and Quebec). As of 2001, more than one million patients had been entered into the database. These studies, by Hartz and colleagues [44] and Bridges and coworkers [45], were performed independently, and both were submitted for publication and published within several months of each other.

In the STS NCD, race is entered as a discrete variable with possible entries including Native American, Hispanic, White, Black, and Other. For the first time in the 1995 STS NCD model, Native American race was an independent predictor of mortality [46]. In the 1996 STS NCD, race, redefined as a dichotomous variable, white versus nonwhite, was an independent predictor of operative mortality [47]. In the study by Hartz and coworkers [44], the population was taken from patients who underwent CABG alone without concomitant procedures, registered in the STS national database from 1994 through 1996. Race was treated as a dichotomous variable, white versus nonwhite. The analysis included 403,974 white and 37,568 nonwhite patients.

Hartz and coworkers [44] found that race, as defined in their study, was a significant predictor of operative mortality. The risk-adjusted operative mortality was 3.9% for nonwhites and 3.3% for whites. When race was removed as a risk factor, patients were then grouped into seven subgroups of increasing predicted operative mortality. Within each of these seven subgroups, race was then analyzed as a risk factor. In the patient subgroups with the highest predicted operative mortality (> 10%), race was not a significant predictor of operative mortality. In the lowest risk subgroups, nonwhites had a statistically significant increase in operative mortality compared with white patients. As in several other studies that evaluated the influence of gender on operative mortality [48, 49], Hartz and associates [44] found that female gender was a significant predictor of operative mortality. There was no significant interaction between the race and gender variables. That is, race and gender exerted similar influences on operative mortality for patients of disparate gender and race, respectively.

Given that blacks have among the highest rates of death from cardiovascular disease in America and the disparate access of blacks to cardiac catheterization, CABG, and PCI, Bridges and colleagues [45] sought to analyze more carefully the effects of black race on CABG operative mortality and morbidity. Therefore, the analysis included only the two largest racial groups (black and white), and all other racial groups were excluded. The study included data obtained from 581,789 patients entered into the STS NCD from 1994 through 1997, of whom 25,850 were black and 555,939 were white. The assessment of procedural morbidity included central neurologic deficit persisting more than 72 hours, pulmonary insufficiency requiring ventilatory support, operative reintervention for bleeding, acute postoperative renal insufficiency, and deep sternal infection involving muscle, bone, or mediastinum. Interactions between race and other risk factors of interest (eg, gender, diabetes, hypertension, cerebrovascular accident, age, reoperation, shock, obesity) were added to the logistic model to determine their significance. Black and white patients were classified into decile groupings based on their preoperative risk score (obtained from the multivariable model with race excluded). Observed operative mortality rates for black and white patients in each risk group were then calculated. To determine whether the difference in mortality rate between blacks and whites was constant across risk score, the race by risk interaction was tested for significance using logistic regression. There were significant differences in the clinical preoperative risk factors for blacks and whites (Table 1). Because of the large number of patients in this analysis, nearly all univariate risk factors differed significantly as a function of race (p < 0.01). Several differences were noteworthy. Black CABG patients were more likely to be female (44.4% vs 27.9%), have hypertension (80.5% vs 62.4%), diabetes (43.8% vs 27.8%), morbid obesity (15.4% vs 11.4%), and renal disease (8.7% vs 2.7%) than white patients. Black patients were also younger, having an average age of 61.5 years old versus 64.8 years old for whites. Blacks were less likely to have their surgery done under urgent, emergent, or salvage conditions, less likely to have had their surgery done following an acute myocardial infarction, and had less New York Heart Association class IV symptoms at the time of bypass. Additionally, black patients did not appear to have more severe coronary disease anatomy or markedly worse left ventricular function (Table 1) [45].


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  		Table 1. Patient Characteristics by Race

 
The operative mortality was 3.83% for blacks and 3.14% for whites (unadjusted OR = 1.23 [1.15 to 1.310]). Similarly, blacks had higher rates of postoperative complications, including stroke (OR = 1.36 [1.25, 1.48]), reoperation for bleeding (OR = 1.10 [1.02 to 1.20]), prolonged ventilation (OR = 1.34 [1.28. 1.40]), renal failure (OR = 1.42 [1.34, 1.51]), and deep sternal wound infection (OR = 1.22 [1.05, 1.40]). In this model, age, reoperation, the need for preoperative intraaortic balloon pump (IABP), and ejection fraction emerged as the strong multivariate predictors of operative mortality. The overall ability of this model to discriminate patients who would live from those who would die was excellent (area under the ROC curve or C-statistic = 0.78). After controlling for the 27 other known risk factors, blacks had a 29% higher operative mortality risk as compared with whites (adjusted OR = 1.29 [1.21, 1.38]). Thus, we concluded that race is an independent risk factor for CABG operative mortality even after accounting for other differences in patient clinical profiles [45].

In contrast to the study by Hartz and colleagues [44] where the race by gender interaction was not significant, in the study by Bridges and coworkers [45] the race by gender interaction was significant, indicating that the difference in mortality between blacks and whites was significantly more pronounced for males than for females. Bridges and coworkers [45] found no significant difference in unadjusted mortality between black and white females (4.49% vs 4.41%; p = NS). In direct analogy to the study by Hartz and colleagues [44], Bridges and coworkers [45] also found that the black/white operative mortality differences were greatest among those patients at lowest predicted operative risk. For example, for patients in the lowest risk decile, the OR for operative mortality was 1.83 whereas among those in the highest risk decile the OR was only 1.03 (Fig 1). And, in fact, a formal test of race by risk interaction was significant, indicating that the difference in mortality rates for blacks and whites was not the same across risk groups [45].



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  		Fig 1. Comparison of the black:white operative mortality odds ratios for different preoperative risk groups.

 

   Comment
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There have been relatively few studies analyzing the results of cardiac surgery in African Americans. None of these studies has evaluated the influence of race on the outcomes of valve repair or replacement therapy. Although a few studies have not found race to be a significant predictor of operative mortality [19, 30], the majority of studies [44, 45, 49] including the largest retrospective study to date [45], found a significant increase in risk-adjusted operative mortality for black (or nonwhite) patients when compared with whites. Based on data derived from the CASS study, long-term risk-adjusted mortality after CABG or medical therapy is higher for blacks than for whites [35]. Also, the effect of gender on CABG operative mortality may be less pronounced for blacks than for whites with similar rates of unadjusted operative mortality for black patients irrespective of gender [45].

The reasons for the higher operative mortality and long-term mortality observed in black patients have not been defined. Several hypotheses have been considered. I considered that perhaps blacks were operated upon disproportionately in geographical regions in which operative mortality was higher or that blacks were operated upon by surgeons with higher adjusted operative mortality rates. Neither of these hypotheses was supported by an analysis of the STS NCD 1994 through 1997 CABG-only data (Duke Clinical Research Institute, unpublished observations). In contrast, Mukamel and associates [19], in an analysis of 11,296 CABG surgeries performed in New York State in 1996 found that nonwhites were significantly more likely to have their CABG performed by surgeons with higher risk adjusted operative mortality.

All of the studies of the results of cardiac surgery in African Americans reviewed, however, suffer from significant limitations including insufficient statistical power, failure to correct for socioeconomic status, health insurance, education, behavioral, dietary and cultural differences, or the inability to adequately consider the significance of racial disparities in postoperative medical care. Based on studies of the African diaspora, and comparisons to the relatively low rates of cardiovascular mortality of populations in Western Africa and elsewhere in the world, the African American diet has been implicated as a potentially modifiable risk factor for cardiovascular disease [50]. The precise features of the African American diet (traditionally high in salt, cholesterol, and saturated fat) responsible for the increased incidence of cardiovascular disease have not been carefully studied [50]. Bridges and cowokers [45] found that the average age of the black CABG patients, 61.5 years old, was significantly lower than the average age of the white patients, 64.8 years old (p = 0.0001). Despite younger age, black patients had similar predicted mortality independent of race. These authors concluded that black patients were generally younger and slightly sicker for their age than the white patients, suggesting that black race may be a surrogate marker for patients with a more rapid rate of progression of CAD, in particular, and vascular disease in general [45].

This finding of potentially more aggressive arteriosclerosis in black patients is also consistent with the observed higher rates of cerebrovascular disease, hypertension, and renal disease in blacks relative to whites. African Americans, in the absence of angiographic evidence of CAD, have a significant reduction in endothelium-independent coronary flow reserve compared with whites [51]. The depressed coronary vascular relaxation in response to both acetylcholine and adenosine in black patients has been associated with the higher prevalence of left ventricular hypertrophy (LVH) seen in blacks [52]. For a given degree of hypertension, black patients are more likely to have significant LVH [53]. In the study by Bridges and coworkers [45], although LVH was not specifically studied, racial differences in operative mortality appeared to be limited to those patients with hypertension. Specifically, whereas hypertensive blacks had significantly higher operative mortality than whites, race was not a significant predictor of surgical outcome among normotensive patients. Thus, one may speculate that LVH may be more prevalent in the black patients studied with hypertension, perhaps increasing the incidence of postoperative arrhythmias or compromising myocardial protection during cardiopulmonary bypass, adversely effecting perioperative survival.


   Conclusions
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In summary, the findings in several studies that African American or nonwhite races are independent predictors of operative mortality after CABG should prompt a more careful search for additional risk factors for CABG operative mortality. These findings should galvanize the search for the additional unrecognized factors that are associated with increased mortality for all patients, irrespective of race. One strategy for identifying these risk factors is to investigate those potential risk factors that have an increased prevalence among black patients with CAD not accounted for in existing multivariate risk models. Given the documented higher prevalence of hypertension and LVH in blacks, the acute outcomes of aortic and mitral valve replacement and repair are likely to vary significantly as a function of race. Race is also likely to exert an independent influence on the longer-term effects of valve surgery on ventricular remodeling, including regression of left ventricular hypertrophy after aortic valve replacement. Because there has not been a study specifically addressing the significance of African American race as an independent predictor of mortality and morbidity following valve surgery, such a study should be undertaken. Finally, in all of the studies reviewed, the differences in operative mortality after CABG are relatively small in absolute terms. Therefore, African American patients should continue to be referred for cardiac surgery based on established clinical criteria independent of race, and efforts to confront racial disparities in access to cardiac catheterization, PCI, CABG, and other cardiac surgical procedures should be intensified.


   References
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