In this study, we investigated the possible role of hypertension in explaining black-white differences in angiographically detectable coronary disease by examining data from an
institutional database in a sample of black and white patients undergoing non-emergent coronary angiography for suspected CAD. Our study confirmed that black patients were significantly less likely to have any detected disease or any significant stenosis (≥50% in LMA or ≥70% in other artery segments) on coronary angiography, but to explore our novel hypothesis, we stratified patients by history of hypertension and then tested the racial differences in angiographic CAD. Among the patients with hypertension, blacks remained less likely than whites to demonstrate any disease or any significant disease. Among the patients without hypertension, however, there was not a significant black-white difference in the rate of detected disease. This finding was supported by the significance of a statistical test of the interaction between hypertension and race for both outcomes. Thus it appears that hypertension may be related to the common finding that
39
blacks undergoing elective catheterization for possible CAD have a lower burden of angiographic disease.
Our sample’s patients resemble those of previous studies assessing black-white differences in CAD risk factors.27, 28 Black patients were more likely to have hypertension, diabetes and elevated BMI than white patients, but the groups had roughly equivalent rates of smoking and hyperlipidemia. In our study stample, we also found, as expected, that traditional CAD risk factors were associated with the outcomes of stenotic disease. Interestingly, non-obese patients had higher rates of detected CAD than obese patients. In several other studies, BMI has been found to have an inconsistent association with the presence of coronary atherosclerosis.29-32
Significance of Results
We are not aware of any studies to date that have examined explanations for the lower incidence of angiographically detected CAD and higher rate of negative diagnostic studies in black patients. Hypertension, and its differential severity between races, provides a plausible explanation for these findings, as its effects and associated symptoms may lead to catheterization in patients without CAD. While hypertension is an established risk factor for CAD itself, its effects extend beyond increasing the likelihood of atherosclerosis or plaque rupture in the coronary arteries, and include both microvascular damage and end-organ disease. Rates of both elevated blood pressure itself and these long-term effects have been shown to be higher in blacks relative to whites.14, 15, 19 Hypertensive disease can certainly mimic CAD on clinical presentation: microvascular disease has been postulated to cause chest pain,21, 22 and LVH can be responsible for a symptomatic presentation including chest pain and ECG changes.11, 23-25 Hypertension can also lead to false positive results on initial diagnostic evaluation; the specificity of many
40
noninvasive tests for CAD have been shown to be quite low in hypertensive patients.33, 34 Moreover, patients with hypertensive heart disease, including LVH and eventual heart failure, may appear to be sicker and at higher risk of cardiac death, prompting clinicians to undertake catheterization.
We feel it is important to examine the potential causes of black-white differences in rates of CAD found during angiography. Coronary angiography is an invasive procedure, and in our sample, black patients—particularly those with a history of hypertension—appear to have a disproportionately high rate of receiving procedures with negative results. Such procedures may be considered unnecessary, costly, potentially harmful, and distracting from other diagnostic strategies appropriate to finding the actual cause of the patient’s symptoms. However, it is important to note that these findings do not temper or dispute the concerning evidence that many blacks in the U.S. do not receive cardiac catheterization when it is clearly indicated.4, 6
Further research, utilizing catheterization findings in conjunction with continuous BP measures over time and data on hypertension-related variables (such as LVH, ECG
abnormalities, age of hypertension onset, endothelial dysfunction and others), may elucidate a set of specific factors that contribute to the disproportionately higher rate of negative studies in this subset of black patients. Such information may eventually support the development of
individualized algorithms for clinical evaluation and management of suspected CAD, taking both race and the impact of hypertension into account.
Limitations
Race classification was based on information from the hospital records rather than self- identification, which, although not ideal, is the case with racial classification in most hospitals in
41
the U.S.35 While hospitals have been shown to misclassify race on a small but significant number of individuals,36 the effect of this misclassification would be nondifferential and tend to minimize rather than exaggerate race group differences.
The use of race as an exposure variable also presents many difficulties. Race is challenging to study as it is a social categorization that does not necessarily reflect genetic variation.37, 38 The diverging effect of hypertension in white and black subjects on angiographic outcomes is complex and likely represents care and access disparities in addition to a myriad of health behavior, socioeconomic, and historical differences between these groups. Biological differences related to hypertension may contribute but are likely not the primary cause of these findings.38, 39 In our study, we included race as a stand-alone variable, without data to assess which aspects of race may be responsible for study findings.
The definition of hypertension as a variable also has important limitations. As it was recorded in the database, patients were grouped according to personal history of hypertension. We did not have information on patient blood pressure over time and could not estimate the direct effect of hypertensive myocardial damage, as it is related to race, on the outcomes.
Conclusions
In this study we assessed how hypertension might explain the racial differences in
likelihood of angiographic disease. We found that black-white differences in angiographic CAD can be demonstrated only for patients with a history of hypertension, with rates of coronary stenosis being equivalent for blacks and whites without hypertension. These findings apply to patients undergoing catheterization suspected to have CAD with no indication for emergent catheterization. These are patients in whom clinical decision making is more difficult, in whom
42
the rate of negative angiography is already generally high,40 and for whom catheterization is elective and clinicians might consider other diagnostic modalities. Among such electively referred patients, it appears that hypertension or its effects may be responsible for the
disproportionate number of negative angiographic studies among blacks. These findings suggest that with additional studies on the connection between race, hypertension and angiographic disease, there may be ways to refine the clinical circumstances under which coronary angiography is most and least likely to contribute important and useful information in the evaluation of chest pain and CAD-like symptoms in black patients.
43
Disclosure: The authors have no conflicts of interest to disclose.
Acknowledgements: This project was funded by University of North Carolina Health Care's Investments for the Future Initiative, through its support for the UNC Eliminate Racial-Ethnic (ERaCE) Disparities Initiative. The authors would like to thank Adam Zolotor and Gary Asher for their thoughtful feedback on an earlier version of this manuscript. Preliminary results of this study were presented at the 2010 NC TraCS Health Disparities Symposium, March 19, 2010 in Chapel Hill, NC.
44 REFERENCES
1. Alderman MH, Cohen HW, Madhavan S. Myocardial infarction in treated hypertensive patients: The paradox of lower incidence but higher mortality in young blacks compared with whites. Circulation. 2000;101(10):1109-1114.
2. Jha AK, Varosy PD, Kanaya AM, et al. Differences in medical care and disease outcomes among black and white women with heart disease. Circulation. 2003;108(9):1089-1094.
3. Clark LT. Issues in minority health: Atherosclerosis and coronary heart disease in African Americans. Med Clin North Am. 2005;89(5):977-1001, 994.
4. Sonel AF, Good CB, Mulgund J, et al. Racial variations in treatment and outcomes of black and white patients with high-risk non-ST-elevation acute coronary syndromes: Insights from CRUSADE (can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines?). Circulation. 2005;111(10):1225-1232.
5. Thomas KL, Al-Khatib SM, Kelsey RC, et al. Racial disparity in the utilization of
implantable-cardioverter defibrillators among patients with prior myocardial infarction and an ejection fraction of <or=35%. Am J Cardiol. 2007;100(6):924-929.
6. Rathore SS, Berger AK, Weinfurt KP, et al. Race, sex, poverty, and the medical treatment of acute myocardial infarction in the elderly. Circulation. 2000;102(6):642-648.
7. Shaw LJ, Shaw RE, Merz CN, et al. Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American
45
College of Cardiology-National Cardiovascular Data Registry. Circulation. 2008;117(14):1787- 1801.
8. Holmes JS, Arispe IE, Moy E. Heart disease and prevention: Race and age differences in heart disease prevention, treatment, and mortality. Med Care. 2005;43(3 Suppl):I33-41.
9. Canto JG, Allison JJ, Kiefe CI, et al. Relation of race and sex to the use of reperfusion therapy in medicare beneficiaries with acute myocardial infarction. N Engl J Med. 2000;342(15):1094- 1100.
10. Heron M, Hoyert DL, Murphy SL, Xu J, Kochanek KD, Tejada-Vera B. Deaths: Final data for 2006. Natl Vital Stat Rep. 2009;57(14):1-134.
11. Bransford TL, Ofili E. The paradox of coronary heart disease in African-American women. J Natl Med Assoc. 2000;92(7):327-333.
12. Onwuanyi AE, Abe O, McMahon DJ, et al. Disparity in frequency of normal coronary artery in black and white patients undergoing cardiac catheterization. Ethn Dis. 2006;16(2):370-374.
13. Whittle J, Kressin NR, Peterson ED, et al. Racial differences in prevalence of coronary obstructions among men with positive nuclear imaging studies. J Am Coll Cardiol.
2006;47(10):2034-2041.
14. Ferdinand KC, Saunders E. Hypertension-related morbidity and mortality in African
46
15. Ferdinand KC, Armani AM. The management of hypertension in African Americans. Crit Pathw Cardiol. 2007;6(2):67-71.
16. Ferdinand KC. Cardiovascular disease in blacks: Can we stop the clock? J Clin Hypertens (Greenwich). 2008;10(5):382-389.
17. Smith SC,Jr, Clark LT, Cooper RS, et al. Discovering the full spectrum of cardiovascular disease: Minority health summit 2003: Report of the obesity, metabolic syndrome, and hypertension writing group. Circulation. 2005;111(10):e134-9.
18. Harshfield GA, Treiber FA. Racial differences in ambulatory blood pressure monitoring- derived 24 h patterns of blood pressure in adolescents. Blood Press Monit. 1999;4(3-4):107-110.
19. Douglas JG, Bakris GL, Epstein M, et al. Management of high blood pressure in African Americans: Consensus statement of the hypertension in African Americans working group of the international society on hypertension in blacks. Arch Intern Med. 2003;163(5):525-541.
20. Berenson GS, Voors AW, Webber LS, Dalferes ER,Jr, Harsha DW. Racial differences of parameters associated with blood pressure levels in children--the Bogalusa Heart Study. Metabolism. 1979;28(12):1218-1228.
21. Cannon RO. Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol. 2009;54(10):877-885.
22. Phan A, Shufelt C, Merz CN. Persistent chest pain and no obstructive coronary artery disease. JAMA. 2009;301(14):1468-1474.
47
23. Estes EH,Jr, Jackson KP. The electrocardiogram in left ventricular hypertrophy: Past and future. J Electrocardiol. 2009;42(6):589-592.
24. Barrios V, Escobar C, Calderon A, et al. Gender differences in the diagnosis and treatment of left ventricular hypertrophy detected by different electrocardiographic criteria: Findings from the SARA study. Heart Vessels. 2010;25(1):51-56.
25. Shoenberger JM, Voskanian S, Johnson S, Ahern T, Henderson SO. Left ventricular
hypertrophy may be transient in the emergency department. West J Emerg Med. 2009;10(3):140- 143.
26. National Cardiovascular Data Registry. NCDR. Available at: http://www.ncdr.com/webncdr/common/. Accessed 11/20, 2009.
27. Kurian AK, Cardarelli KM. Racial and ethnic differences in cardiovascular disease risk factors: A systematic review. Ethn Dis. 2007;17(1):143-152.
28. Curry CL, Oliver J, Mumtaz FB. Coronary artery disease in blacks: Risk factors. Am Heart J. 1984;108(3 Pt 2):653-657.
29. Rossi R, Iaccarino D, Nuzzo A, et al. Influence of body mass index on extent of coronary atherosclerosis and cardiac events in a cohort of patients at risk of coronary artery disease. Nutr Metab Cardiovasc Dis. 2009.
30. Auer J, Weber T, Berent R, et al. Obesity, body fat and coronary atherosclerosis. Int J Cardiol. 2005;98(2):227-235.
48
31. Phillips SD, Roberts WC. Comparison of body mass index among patients with versus without angiographic coronary artery disease. Am J Cardiol. 2007;100(1):18-22.
32. Niraj A, Pradhan J, Fakhry H, Veeranna V, Afonso L. Severity of coronary artery disease in obese patients undergoing coronary angiography: "Obesity paradox" revisited. Clin Cardiol. 2007;30(8):391-396.
33. Prisant LM, Frank MJ, Carr AA, von Dohlen TW, Abdulla AM. How can we diagnose coronary heart disease in hypertensive patients? Hypertension. 1987;10(5):467-472.
34. Fragasso G, Lu C, Dabrowski P, Pagnotta P, Sheiban I, Chierchia SL. Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress
echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test. J Am Coll Cardiol. 1999;34(2):441-447.
35. Hasnain-Wynia R, Pittman M, Pierce D. Who, when and how: The Current State of Race, Ethnicity, and Primary Language Data Collection in Hospitals. The Common Wealth Fund; 2004.
36. Blustein J. The reliability of racial classifications in hospital discharge abstract data. Am J Public Health. 1994;84(6):1018-1021.
37. Sue S, Dhindsa MK. Ethnic and racial health disparities research: Issues and problems. Health Educ Behav. 2006;33(4):459-469.
38. Gravlee CC. How race becomes biology: Embodiment of social inequality. Am J Phys Anthropol. 2009;139(1):47-57.
49
39. Kaufman JS, Cooper RS. Race in epidemiology: New tools, old problems. Ann Epidemiol. 2008;18(2):119-123.
40. Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362(10):886-895.
50 TABLES
Table 1. Patient Characteristics by Race
Characteristic Black mean
or % (n=1,203) White mean or % (n=2,538) p-value Age in years 54.5 59.9 <0.001 % Male 45.3 55.6 <0.001 BMI (kg/m²) 32.4 29.0 <0.001
% with smoking history 58.0 60.0 0.270
% with hypertension 81.6 65.7 <0.001
% with hyperlipidemia 48.4 49.4 0.588
% with diabetes 35.5 21.7 <0.001
% with positive family history of CAD
31.5 39.8 <0.001
% with CHF 25.6 13.1 <0.001
BMI=body mass index
CAD=coronary artery disease
51
Table 2. Associations Between Patient Characteristics and Angiographically Detected Stenosis
CharacteristicAge (10 years)
Any Stenosis
(% with outcome))
p-value Significant Stenosis
(% with outcome) p-value Age ≥60 (n=1,702) <60 (n=2,039) 79.0% 50.6% <0.001 41.1% 23.2% <0.001 Sex Male (n=1,955) Female (n=1,786) 71.1% 55.3% <0.001 39.2% 22.8% <0.001 BMI (kg/m²) ≥30 (n=1,800) <30 (n=1,921) 60.2% 66.6% <0.001 26.7% 35.6% <0.001 Smoking hx Former/Current (n=2,106) Never (n=1,444) 67.1% 56.8% <0.001 35.8% 25.9% <0.001 Hypertension Yes (n=2,598) No (n=1,072) 68.4% 51.5% <0.001 34.3% 23.6% <0.001 Hyperlipidemia Yes (n=1,703) No (n=1,769) 73.5% 54.0% <0.001 38.7% 26.1% <0.001
52 Diabetes Yes (n=958) No (n=2,710) 72.6% 60.4% <0.001 37.6% 28.9% <0.001 Family hx of CAD Yes (n=1,262) No (n=2,137) 65.5% 62.0% 0.039 33.0% 29.7% 0.043 CHF Yes (n=624) No (n=3,024) 55.3% 65.2% <0.001 22.0% 33.1% <0.001
BMI=body mass index
CAD=coronary artery disease
53
Table 3. Odds Ratios (OR) of Angiographically Detected Stenosis for Black Patients Relative to Whites, Stratified by Hypertension*
Characteristic OR of any stenosis** p-value^ OR of sign. stenosis** p-value^ Patients with hypertension (n=2,112) 0.50 (0.41-0.62) <0.001 0.47 (0.38-0.59) <0.001 Patients without hypertension (n=909) 0.93 (0.63-1.36) 0.699 0.95 (0.60-1.53) 0.846
*Adjusted for age, sex, hyperlipidemia, diabetes, smoking status, family history **OR presented for blacks relative to whites