Usefulness of Breast Arterial Calcium Detected on Mammography for Predicting Coronary Artery Disease or Cardiovascular Events in Women With Angina Pectoris and/or Positive Stress Tests
Article Outline
Breast arterial calcium (BAC) has been suggested as a marker and predictor of cardiovascular risk and coronary artery disease (CAD). However, an association between BAC and these cardiovascular end points has not been fully elucidated in patients undergoing cardiac catheterization. Consecutive patients undergoing mammography and cardiac catheterization within a 36-month period were retrospectively evaluated through chart review. Cardiac catheterization films and mammograms from 94 patients were independently reviewed for the presence of CAD and BAC, respectively. Cardiovascular risk factors, history of revascularization, and history of myocardial infarction were compared between women with and without BAC. BAC was more prevalent in older women (mean age 69 ± 10 vs 63 ± 11 years, p = 0.02). Aside from an inverse correlation with smoking, there was no difference in the presence of CAD or cardiovascular risk factors between patients with and without BAC. Patients with BAC had a lesser history of acute myocardial infarction (21% vs 41%, p <0.05) and were less likely to undergo revascularization (23% vs 43%, p <0.05). In conclusion, BAC was not positively associated with cardiovascular risk factors, documented CAD, or acute cardiovascular events, suggesting that the presence of BAC as determined by mammography is not a useful predictor of CAD in intermediate- to high-risk patients.
Previous studies have attempted to document a relation between breast arterial calcium (BAC) and coronary artery disease (CAD) using the presence of coronary calcium as a marker of CAD,1 or alternatively have explored the potential association between BAC and cardiovascular events and disease through questionnaires assessing patient history of abnormal angiographic findings, coronary heart disease, previous myocardial infarction (MI), and angina pectoris.2, 3, 4, 5 Few previous studies have examined the utility of BAC for prediction of CAD in conjunction with independent review of catheterization films, with 1 finding no correlation between BAC and documented CAD, whereas others have reported a significant association.6, 7, 8 To further elucidate the usefulness of BAC to predict CAD and cardiovascular events, we undertook a study in women who had undergone mammography and cardiac catheterization by performing independent chart review and review of catheterization films to characterize associations between BAC and CAD, MI, and/or coronary revascularization events.
Methods
Patient charts from consecutive women having undergone mammography and cardiac catheterization within a 36-month period were identified from the cardiology database at our institution and reviewed retrospectively for baseline characteristics (age, cardiovascular risk factors, co-morbidities) and clinical events of MI, coronary angioplasty, stent placement, or coronary artery bypass grafting. Patients were referred for cardiac catheterization based on positive stress test results and/or anginal symptoms. Selective coronary angiography was performed for evaluation of known or suspected CAD in all cases. Cardiac catheterization films were retrospectively reviewed in blinded fashion by an experienced interventional cardiologist and evaluated for CAD, which was defined as ≥50% luminal narrowing of a major epicardial and/or branch coronary artery, or any degree of coronary stenosis. A separate analysis was performed for coronary calcium from angiographic films.9 Mammograms from 1998 to 2003 were digitized (R2 Technology, Hologic, Co., Sunnyvale, California) and reanalyzed for breast arterial microcalcification on state-of-the-art equipment (Senographe 2000D, GE Healthcare, United Kingdom) with high sensitivity for any degree of calcium by an experienced board-certified radiologist who was blinded to the results of patients' cardiac catheterization results and history. Ethical approval was obtained from William Beaumont Hospital's (Royal Oak, Michigan) ethics committee (Human Investigational Committee Number 2004-066). The conduct of this study was consistent with the principles of the Declaration of Helsinki.
Patient charts were reviewed for a history of the following atherosclerotic risk factors: hypercholesterolemia (defined as patient history of hypercholesterolemia and/or use of cholesterol-lowering medication), current or previous (≥6 months) smoking, hypertension (defined as patient history of hypertension and/or use of antihypertensive medication), and diabetes mellitus (defined as patient history of diabetes and/or use of oral hypoglycemic medication or insulin). A history of hormone replacement therapy, chronic kidney disease (estimated glomerular filtration rate <30 ml/min by the Cockcroft-Gault method10), and a patient's body mass index were recorded, along with a history of MI (defined as positive cardiac enzyme levels or typical electrocardiographic changes in the setting of symptoms consistent with cardiac ischemia) and revascularization events including angioplasty, stenting, or coronary artery bypass grafting.
We compared data from patients with and without BAC for baseline demographics, cardiac risk factors, CAD, MI, and revascularization events. Categorical variables were reported as counts and percent frequencies and were examined using Pearson chi-square test where appropriate (expected frequency >5) or alternatively using Fisher's exact test. Continuous variables were examined using Wilcoxon rank-sum tests. All continuous variables are presented as means ± SDs. All analyses used SAS 9.2 for Windows (SAS Institute, Cary, North Carolina).
Results
Complete datasets were available from 94 patients; the mean time between mammography and catheterization was 15.7 ± 10.5 months. Fifty-seven patients had positive results for BAC and 37 had negative results (Table 1). BAC was more prevalent in older women (p = 0.02). There was no difference in the history of hypertension, diabetes, or hypercholesterolemia between BAC-positive and BAC-negative groups. Furthermore, there was no significant difference in angiographic evidence of coronary artery stenosis, defined as ≥50% (clinically significant CAD) or >0% stenosis, in patients with BAC compared to those without. Presence of coronary calcium was no greater in patients with BAC compared to those without. Patients with BAC were not more likely to use hormone replacement therapy or to have chronic kidney disease compared to those without BAC. Similar to findings in previous studies,1, 6, 7 there was a negative association between BAC and current or previous smoking (p = 0.015). With regard to cardiovascular events and revascularization, patients with BAC had a lesser incidence of MI (p <0.05; Figure 1) and were less likely to undergo revascularization procedures including coronary angioplasty, stenting, or coronary artery bypass grafting (p <0.05).
Table 1. Demographics and co-morbidities in patients with and without breast arterial calcium
| Parameter | Total (n = 94) | BAC | p Value | |
|---|---|---|---|---|
| Yes | No | |||
| (n = 57) | (n = 37) | |||
| Age (years) | 66.7 ±10.5 | 68.9±9.7 | 63.2±10.9 | 0.021 |
| Body mass index (kg/m2) | 28.0±5.9 | 28.1±5.5 | 27.9±6.6 | 0.71 |
| History of | ||||
| Hypertension | 68(72%) | 41(72%) | 27(73%) | 0.91 |
| Hypercholesterolemia | 50(53%) | 30(53%) | 20(54%) | 0.89 |
| Current or previous smoking | 23(24%) | 9(16%) | 14(38%) | 0.015 |
| Diabetes mellitus | 20(21%) | 13(23%) | 7(19%) | 0.65 |
| Chronic kidney disease | 9(10%) | 5(9%) | 4(11%) | 0.73 |
| Hormone replacement therapy | 36(38%) | 19(33%) | 17(46%) | 0.22 |
| Coronary artery stenosis ≥50% | 53(56%) | 32(56%) | 21(57%) | 0.95 |
| Coronary artery stenosis >0% | 63(67%) | 39(68%) | 24(65%) | 0.72 |
| Coronary calcium | 47(51%) | 28(50%) | 19(53%) | 0.79 |
Figure 1.
Women without BAC had more cardiovascular events than those without (* p <0.05 using Pearson chi-square test).
Discussion
In this retrospective cohort study of women who underwent cardiac catheterization and mammography within a 36-month period, presence of BAC was not associated with presence of CAD documented at cardiac catheterization when using ≥50% stenosis or any degree of stenosis as criteria for CAD. Our findings agree with those of Henkin et al7 who also reviewed catheterization films and used ≥50% stenosis to define CAD. In contrast, Fiuza Ferreira et al6 uncovered a positive association between BAC and CAD, with CAD defined as any degree of existing stenosis. Our data, when defining CAD with these criteria (>0% stenosis), did not yield a positive association. A third study in higher-risk women undergoing cardiac catheterization identified a relation between BAC and CAD ('50% stenosis) in younger women, but results were confounded by the presence of diabetes, and furthermore BAC exhibited a low sensitivity for predicting CAD.8 In addition to studies using cardiac angiography, 2 reports have identified a positive correlation between BAC with CAD defined by the presence of coronary calcium assessed by multiscan computer tomography.1, 11 In 1 of these studies BAC was found to correlate with a future risk of coronary calcium, which was obtained an average of 9 years later. The investigators noted that age was the most important predictor of BAC and coronary calcium.1 We analyzed our data for the presence of coronary calcium, obtained at the time of coronary angiography, and found no correlation between BAC and CAD.
Additional studies have evaluated whether traditional cardiac risk factors or newer biomarkers, such as C-reactive protein, correlate with BAC in subjects undergoing screening mammography. Some of these, notably those using self-reported questionnaires, have reported an association between BAC and risk factors,2, 3, 4, 5 especially in diabetics,12, 13, 14 whereas other studies have failed to confirm this association.1, 15, 16, 17, 18 Our data did not yield a positive correlation between BAC and cardiovascular risk factors in patients referred for cardiac catheterization.
The potential relation between cardiovascular events (e.g., coronary artery bypass grafting, stroke, MI, and/or heart failure) or all-cause mortality and BAC has also been examined. Some studies have reported an association2, 3, 4, 5, 13, 14, 18 whereas others have not.7, 16, 19 Those reporting an association between BAC and cardiovascular events included subjects who, almost without exception, used self-reported questionnaires rather than chart review to document events. In contrast, 2 studies using chart review to evaluate high-risk patients reported no association.7, 19 We, however, observed a weak inverse relation between BAC and MI and between BAC and revascularization.
Lack of a clear association between BAC and coronary disease may reflect differences in the pathogenic nature of calcium deposition in breast arteries versus coronary arteries. Coronary calcium is localized to the intima, where it contributes to arterial narrowing, whereas BAC is uniformly located in the media, where it is considered a benign entity not associated with inflammation or plaque instability.15 The present data and results from other studies using chart review in high-risk populations do not support an association between BAC and several markers of cardiovascular disease, furthering doubts on the usefulness of mammography in predicting CAD in this population.
Limitations of this study include the small number of subjects and that all women were referred for catheterization and therefore were at intermediate to high risk for CAD. Use of BAC on screening mammogram as a predictor of CAD in asymptomatic women was not explored and limits our findings to higher-risk patient populations. There was no long-term follow-up in our study, limiting our findings with regard to long-term cardiovascular events.
References
- . Breast arterial calcifications are correlated with subsequent development of coronary artery calcifications, but their aetiology is predominantly different. Eur J Radiol. 2007;63:396–400
- . Breast artery calcium on routine mammography as a potential marker for increased risk of cardiovascular disease. Am J Cardiol. 2000;86:216–217
- . Breast vascular calcification and risk of coronary heart disease, stroke, and heart failure. J Womens Health. 2004;13:381–392
- . Breast arterial calcifications (BACs) found on screening mammography and their association with cardiovascular disease. Menopause. 2008;15:276–281
- . Mammograms may convey more than breast cancer risk: breast arterial calcification and arterio-sclerotic related diseases in women of the DOM cohort. Eur J Cancer Prev. 1996;5:483–487
- . Correlation between intramammary arterial calcifications and CAD. Acad Radiol. 2007;14:144–150
- . Lack of association between breast artery calcification seen on mammography and coronary artery disease on angiography. J Med Screen. 2003;10:139–142
- . Breast arterial calcification: association with coronary artery disease (Work in progress). Radiology. 1995;194:181–183
- . Detecting coronary artery calcification. Clin Cardiol. 2000;23:717–718
- . Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41
- . Association of breast arterial calcifications detected by mammography and coronary artery calcifications quantified by multislice CT in a population of post-menopausal women. Radiol Med. 2003;106:305–312
- . Breast arterial calcifications associated with diabetes and hypertension. J Diabetes Complications. 2004;18:363–366
- . Breast arterial calcifications: association with diabetes mellitus and cardiovascular mortality (Work in progress). Radiology. 1996;201:75–78
- . Arterial calcification found on breast cancer screening mammograms and cardiovascular mortality in women: the DOM project (Doorlopend Onderzoek Morbiditeit en Mortaliteit). Am J Epidemiol. 1998;147:333–341
- . Arterial calcium on mammograms is not associated with inflammatory markers for heart disease risk. Heart. 2006;92:541–542
- . Arterial calcifications seen on mammograms: cardiovascular risk factors, pregnancy, and lactation. Radiology. 2006;240:33–38
- . Breast arterial calcification in association with diabetes mellitus: too weak a correlation to have clinical utility. Radiology. 1985;155:577–579
- . How predictive is breast arterial calcification of cardiovascular disease and risk factors when found at screening mammography?. AJR Am J Roentgenol. 2006;187:73–80
- . Prevalence and determinants of breast arterial calcium in women at high risk of cardiovascular disease. Am J Cardiol. 2004;94:655–659
This study was supported by the Ministrelli Women's Heart Center, William Beaumont Hospital, Royal Oak, Michigan.
PII: S0002-9149(09)02410-2
doi:10.1016/j.amjcard.2009.09.039
© 2010 Published by Elsevier Inc.
