- Email: [email protected]
Relationship between the arterial calcification detected in mammography and coronary artery disease
European Journal of Radiology 63 (2007) 391–395
Relationship between the arterial calcification detected in mammography and coronary artery disease b, ¨ Ugur Topal a,∗ , Aysel Kaderli b , Naile Bolca Topal a , B¨ulent Ozdemir Dilek Yes¸ilbursa b , Jale Cordan b , B¨ulent Ediz c , Ali Aydınlar b a b
Department of Radiology, Uludag University, Medical School, G¨or¨ukle Campus, 16059 Bursa, Turkiye Department of Cardiology, Uludag University, Medical School, G¨or¨ukle Campus, 16059 Bursa, Turkiye c Department of Statistics, Uludag University, Medical School, G¨ or¨ukle Campus, 16059 Bursa, Turkiye Received 16 October 2006; received in revised form 25 January 2007; accepted 26 January 2007
Abstract Objective: Arterial calcification is frequently encountered in mammography. The frequency of breast arterial calcification (BAC) increases with increasing age. Studies have shown that BAC is seen more frequently among the people who are under the risk of coronary artery diseases (CAD) such as diabetes and hypertension. The objective of this study is to investigate the relationship between the arterial calcification detected in mammography and the CAD. Material and methods: Screening mammography was performed in 123 women above the age of 40 years who had been examined with coronary angiography for the evaluation of CAD. The presence of BAC, number of affected vessels, and the distribution of calcification in the vessel wall were evaluated in the mammography. Subjects were questioned in terms of the cardiovasculary risk factors. The severity of CAD was evaluated according to the Gensini scoring. In addition, the number of blood vessels with stenosis of more than 50% was used as the vascular score. The correlation between Gensini and the vascular scores, and BAC was statistically evaluated using Mann–Whitney U and Kruskal–Wallis tests. Results: Eighty (65%) of 123 patients had CAD. BAC was detected in the mammography of 49 (39.8%) subjects. The ages and duration of menopause of the cases with BAC were significantly higher than those without BAC (p < 0.001). There was an almost significant correlation between the BAC and Gensini scores (p = 0.059). There was a significant increase in the frequency of BAC among subjects with more than two vessels with stenosis (p = 0.033). Conclusion: Frequency of BAC increases with increasing age. BAC is also frequently seen in subjects having severe coronary artery disease. Although increasing age may be a factor increasing the frequency of BAC, BAC may also be an indicator of CAD. Therefore, the mentioning of arterial calcification in mammography reports may be important in warning the clinician in terms of CAD. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Arterial calcification; Breast; Mammography; Coronary artery disease
1. Introduction Arterial calcification is a common finding in screening mammography. The frequency of breast arterial calcification (BAC) increases with increasing age and is seen in 9–12% of women above the age of 50 [1,2]. Although BAC is a finding of ageing, it may also emerge as an indicator of diabetes mellitus (DM), hypertension and other vascular diseases [3–5]. BAC is considered to be an independent risk factor for coronary artery disease
∗
Corresponding author. Tel.: +90 224 4428845; fax: +90 224 4428142. E-mail address: [email protected] (U. Topal).
0720-048X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2007.01.035
(CAD) in old age especially for the women with DM [4] and cardiovascular mortality is found to be 40% higher among the patients with BAC [6]. As we already know, calcification is useful in predicting the atherosclerotic plaque burden in the epicardial coronary arteries in the patients with no complaints [7]. There is a strong correlation between the frequencies of coronary artery calcification and cardiovascular diseases [8]. Similar to BAC, the frequency of coronary artery calcification increases with age [9]. Various studies have stated that coronary artery calcification scoring may be a useful predictor of cardiovascular diseases [10,11]. On the other hand, calcification was detected in the aortic wall of 33% of the subjects, who underwent computed tomography exam-
392
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
ination of the thorax for some cause (tuberculosis, malignity, etc.) [12]. Calcification in the aortic wall is shown to be related to age, hypertension, DM, smoking and alcohol consumption, hyperlipidemia, obesity and other vascular diseases [13]. The presence of calcification in the aortic wall in women, and its presence in peripheral arteries in diabetic patients increase the risk of death by 1.5 times [14]. Markopoulos et al., showed that there is a correlation between BAC, detected in mammography, and systemic vascular diseases, and argued that BAC is an indicator of systemic vascular atherosclerosis [15]. Several studies have argued that arterial calcifications may be considered as an indicator of cardiovascular events [4,6,8]. In our study, we aimed to investigate the relationship between BAC, detected in mammography, and coronary atherosclerosis among women above the age of 40 who were examined with coronary angiography. 2. Material and methods One hundred and twenty-three females, aged between 40 and 77 (mean 56.84 ± 9.54), who underwent coronary angiography were included into the study. One hundred and fifteen of the subjects were in their post-menopausal period. The duration of menopause ranged from 3 months to 35 years (mean 10.24 ± 9.08). None of the subjects had history of hormone replacement therapy (HRT). Subjects were evaluated in terms of the risk factors of coronary artery disease (hypertension, DM, hyperlipidemia, obesity, family history, and smoking), heart diseases (heart failure, known coronary artery disease), coronary artery disease equivalents (DM, carotid artery disease, abdominal aortic aneurysm, peripheral artery disease) and any therapies they received. The clinical forms of CAD were classified as stable angina, acute coronary syndrome and previous history of myocardial infarction. Coronary angiography was performed with the Judkins method. Angiography was performed due to the history of myocardial infarction in 15 patients, acute coronary syndrome in 17 patients and the history of chest pain with positive exercise stress test in 91 patients. Angiography images were evaluated by two experienced cardiologists. Evaluation of the coronary atherosclerosis was performed in accordance with the Gensini scoring [16,17]. The severity of stenosis in the lumen of the coronary artery, the particular blood vessels in which stenosis occurred, and their location are all taken into account in the Gensini scoring. According to this, the coronary artery is separated into 15 segments, and coefficients ranging from 0.5 and 5.0 are assigned to each artery (Table 1). Percentages of stenosis are evaluated by giving numbers from 0 to 32. Scoring is performed in accordance with the degree of severity of stenosis. The coefficients that are given according to the localization and percent of stenosis of each lesion are multiplied with each other, and this value is taken as the total score of that particular lesion. Gensini score is obtained by the addition of the total score that is calculated for each coronary stenosis (Table 1). We also calculated the vascular score that is considered to be another predictor of the severity of coronary artery disease [18]. Vascular score was expressed as the number of blood vessels constricted more than
Table 1 Calculation of the Gensini scoring index Score Lumen stenosis (%) <25 26–50 51–75 76–90 91–98 99 100
Coefficient
0 1 2 4 8 16 32
Left main coronary artery
5
Left anterior descending artery Proximal Middle Distal
2.5 1.5 1
First diagonal Second diagonal
1 0.5
Circumflex Proximal Middle Distal
1.5 1 1
Obtus marginal Posterolateral
1 0.5
Right coronary artery Proximal Middle Distal
1 1 1
Posterior descending artery
1
50%. Vascular score was defined as non-critical lesion in the cases with stenosis less than 50%. Subjects were divided into three groups as non-critical, single blood vessel involvement, and multiple (≥2) blood vessel involvement according to their vascular scores. Screening mammography was performed to subjects within 2–10 days after coronary angiography procedure. Permission was obtained from the ethics committee of the hospital. Subjects were informed about the study and its procedures, and an informed consent was obtained from each patient. Mammography examinations were evaluated by an experienced radiologist, who was blinded to the clinical features of the patients, according to the BI-RADS (breast imaging and reporting data system) classification recommended by the American College of Radiology [19]. The presence of arterial calcification, the number of calcified blood vessels, whether one or both breast was involved, and the distribution of calcification in the vessel wall were investigated. The distribution of vascular calcification in the vessel wall was evaluated in terms of its involvement of the entire vessel wall either continuously or discontinuously. If the vessel wall was calcified throughout its length, it was categorized as continuous involvement (Fig. 1). If the whole vessel wall was not calcified and there were interruptions between calcifications, then it was categorized as discontinuous involvement (Fig. 2). In the presence of both continuous and discontinuous involvement of more than one vessel in one breast, it was accepted as continuous involvement.
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
393
The presence of BAC, involvement of one or both breasts, the number of blood vessels involved and the distribution of calcification was compared with the Gensini scores. Statistical analysis was performed by entering the data into SPSS 13.0. Data was presented as means ± standard deviation. Mann–Whitney U and Kruskal–Wallis tests were used in the evaluation. Statistical significance was taken as p < 0.05. 3. Results
Fig. 1. The vessel walls were calcified continuously. Calcifications were seen throughout the vessel wall.
Coronary artery disease has been detected in 80 subjects (65%) out of 123 included in the study. Fifteen of the subjects (12%) had a history of past myocardial infarction, 23 (19%) had a diagnosis of stable angina pectoris, and 17 patients had been diagnosed with acute coronary syndrome. When evaluated in terms of cardiovascular risk factors, 92 (74.8%) had hypertension, 16 (13%) smoked cigarette, and 28 (22.7%) a family history. Average LDL cholesterol level was calculated to be 125.29 ± 34.64. While Gensini scores ranged from 0 to 188, the mean score was 14.79 ± 29.36. In terms of vascular scores, 32 (26%) had a non-critical, 18 (15%) single vessel, and 30 (24%) multiple vessel coronary artery disease (blood vessel score ≥2). According to the mammography examinations, no significant findings of malignancy were determined in any of the cases. BAC was detected in a total of 49 (39.8%) subjects; in one breast in 16 (13%) subjects and in two breasts in 33 (26.8%) subjects. Of the subjects with BAC, 22 (44.9%) had calcifications in one blood vessel, 15 (30.6%) had calcifications in two blood vessels, and 12 (24.5%) had calcification in more than two vessels. Calcifications in the vessel wall were evaluated as discontinuous in 29 (59.2%) subjects, and continuous in 20 (40.8%) cases. Ages and durations of menopause of the subjects who were diagnosed with BAC were higher than those without BAC in a statistically significant manner (p < 0.001). Ages of the cases with BAC ranged from 48 to 77, and the mean value was 63.85 ± 7.16 years. Ages of the subjects who did not have BAC ranged from 40 to 73, and the mean value was 52.34 ± 7.69 years. The average duration of menopause for the group with BAC was 15.60 ± 8.87 years, whereas it was 6.39 ± 7.11 years for the group without BAC. There was no statistically significant difference between the two groups in terms of hypertension, DM, Table 2 Distribution of the demographic features and cardiovascular risk factors of the subjects by the presence of BAC BAC (+) (n = 49) (%)
Fig. 2. The vessel walls were calcified discontinuously. Only some parts of the wall were calcified; there were interruptions between calcifications.
Age (years) Duration of menopause (years) DM Hypertension Smoking Family history LDL (mg/dl) HDL (mg/dl)
BAC (−) (n = 74) (%)
63.85 ± 7.16 15.60 ± 8.87
52.34 ± 7.69 6.39 ± 7.11
16 (33) 40 (82) 3 (6) 22 (44) 131.59 ± 31.10 47.39 ± 9.44
17 (23) 52 (70) 10 (13) 27 (37) 122.28 ± 36.14 47.69 ± 8.36
BAC: breast arterial calcification; NS: not significant.
p <0.001 <0.001
NS NS NS NS NS NS
394
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
Table 3 The relationship between BAC and CAD
Presence of CAD Non-critical Single vessel involvement Multiple vessel involvement Gensini score
BAC (+) (n = 49) (%)
BAC (−) (n = 74) (%)
p
36 (73) 11 (22) 6 (13)
44 (60) 21 (29) 11 (15)
NS NS NS
19 (38)
12 (16)
0.033
17.47 ± 28.13
13.00 ± 30.19
0.059
BAC: breast arterial calcification; CAD: coronary artery disease; NS: not significant.
smoking, family history, and cardiovascular risk factors such as hyperlipidemia (Table 2). When the cases were evaluated in terms of the correlation between the Gensini scoring, which indicates the severity of coronary artery disease, and BAC, an almost statistically significant relationship was established (p = 0.059). The frequency of BAC showed a significant increase in subjects who had a vascular score of 2 or more (p = 0.033) (Table 3). There was no significant correlation between BAC and the clinical presentation of coronary artery disease, and the drug treatment that is performed. There was no correlation between the number of calcified blood vessels detected in mammography, the form of calcification and its distribution, and the Gensini scoring. 4. Discussion Arterial calcifications, which are commonly detected in mammography, develop as a result of extensive calcification of the medial layer (M¨onckeberg’s arteriosclerosis). Medial calcification is a common finding of extremity radiographs and resembles railroad tracks or rings in enface images. It is thought that medial arterial calcification is a result of the aging process and thought as an unimportant finding. However many studies have shown that many elderly male patients having DM, renal insufficiency, hypertension, and familial amyloidosis with polyneuropathy also have calcifications [20]. Baum et al. have suggested that BAC found in mammography might point to clinically undiagnosed cases of DM [3]. Nevertheless, Sickles and Galvin suggested that BAC should be considered more of an indicator of old age than of diabetes [2], since BAC rate for 70-year-old female patients is 28 times higher than that of 50-year-old (1.3% and 36%, respectively). It has been suggested in the succeeding studies that hormonal factors, such as pregnancy and early menopause, as well as age also contribute in the formation of BAC [21,22]. Based on these findings it has been concluded that hormone replacement therapy can undermine the formation of BAC, hence prevent the formation post-menopausal cardiovascular diseases [22,23]. In our series, the rate of BAC also increased with age (Table 2). The average age for BAC was 63.85 ± 7.16 and the average age of the group without BAC was 52.34 ± 7.69. The difference between the two groups was found to be statistically significant (p < 0.001). Another factor that significantly correlated with BAC was the duration of menopause (Table 2).
As the duration of menopause increased, the rate of BAC also increased (Table 2). No statistically significant relationship was found between BAC and cardiovascular risk factors such as hypertension, DM, smoking, family history, and hyperlipidemia. Findings of various studies indicate that BAC can be an independent risk factor for CAD [4,14,24]. Moshyedi et al. stated that BAC correlated strongly with DM and CAD in their study conducted on 182 patients less than 59 years of age who underwent coronary angiography with the suspicion of CAD. However, the abundance of CAD cases in the sample of non-BAC patients under 59 years of age indicates that BAC has a low sensitivity in terms of CAD, which renders it unsuitable to be used as a screening test [4]. The correlation between CAD and BAC decreases with increasing age. In women above the age of 59, CAD is less common in the presence of BAC, regardless of diabetes status. These results suggest that other factors, in addition to old age, are involved in the formation of BAC [4]. Henkin et al. have, however, stated that BAC did not have a significant difference among those with and without the angiographic findings of CAD [25]. Similar findings of correlation of BAC with age related CAD has also been reported in other arterial systems [26]. The calcifications detected in abdominal aorta have been defined as a possible indicator of increased risk of disease in young males [26]. Arterial calcifications become more intense, however less correlated with risk, with increasing age. Similarly, the presence of calcifications in thoracic aorta increases the risk of CAD in males and females under the age of 65 [27]. In our study, Gensini scoring and vascular scoring were both used in evaluating the severity of coronary artery diseases. As seen in Table 1, Gensini scoring is derived by taking into consideration the particular blood vessel in which the atherosclerotic lesion is located, the localization of the lesion in the blood vessel and the lesion’s severity. By using Gensini scoring, vascular stenosis less than 50% were also taken into consideration [16–18]. On the other hand, vascular scoring is a scoring system which considers only the critical lesions. As indicated in Table 3, according to our results, there is an almost significant statistical relationship between the Gensini scoring and BAC (p = 0.059). In subjects with many vessel involvement according to the vascular scoring, BAC frequency shows a statistically significant increase (p = 0.033). Therefore, BAC may be an indicator of severe coronary artery disease in women above 40 years of age. However, as we already know the frequency of both CAD and BAC increases with increasing age, therefore the results may be biased because of the higher mean age of the patients in CAD group. There are some limitations of our study. One of these is that the study has focused on patients suspected to have CAD who underwent coronary angiography. This sample will not be representative of the general population. Another shortcoming is the small size of our sample. So, this study needs to be verified using series with larger sample size. In conclusion, detection of BAC in mammography increases with age and duration of menopause. BAC is also frequent in subjects having severe coronary artery disease. Although increasing age may be a factor increasing the frequency of BAC, BAC may
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
also be a strong indicator of CAD. Therefore, the mentioning of arterial calcification in mammography reports may be a useful notice for the clinician as a potential indicator of CAD. However, our results should be supported with further studies with larger series. References [1] Schmitt EL, Threatt BA. Mammographic intra-arterial calcifications. J Can Assoc Radiol 1984;35:14–6. [2] Sickles EA, Galvin HB. Breast arterial calcification in association with diabetes mellitus: too weak a correlation to have clinical utility. Radiology 1985;155:577–9. [3] Baum JK, Comstock CH, Joseph L. Intramammary arterial calcifications associated with diabetes. Radiology 1980;136:61–2. [4] Moshyedi AC, Puthawala AH, Kurland RJ, O’Leary DH. Breast arterial calcification: association with coronary artery disease. Radiology 1995;194:181–3. [5] C ¸ etin M, C ¸ etin R, Tamer N. Prevalence of breast arterial calcification in hypertensive patients. Clin Radiol 2004;59:92–5. [6] Kemmeren JM, Beijerinck D, vanNoord PAH, et al. Breast arterial calcifications: association with diabetes mellitus and cardiovascular mortality. Radiology 1996;201:75–8. [7] Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243–52. [8] Hosoi M, Sato T, Yamagami K, et al. Impact of diabetes on coronary stenosis and coronary artery calcification detected by electron-beam computed tomography in symptomatic patients. Diab Care 2002;25:696–701. [9] Allison MA, Wright CM. Age and gender are the strongest clinical correlates of prevalent coronary calcification (R1). Intern J Cardiol 2005;98:325–30. [10] Agaston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1999;15:827–32. [11] Haberl R, Becker A, Leber A, et al. Correlation of coronary calcification and angiographically documented stenosis in patients with suspected coronary artery disease: results on 1764 patients. J Am Coll Cardiol 2001;37:451–7.
395
[12] Itani Y, Watanabe S, Masuda Y. Aortic calcification detected in a mass chest screening program using a mobile helical computed tomography unit. Circ J 2004;68:538–41. [13] Gorich J, Zuna I, Merle M, et al. Aortic calcification in CT: correlation with risk factors and cardiovascular disease. Radiologie 1989;29:614–9. [14] Kemmeren JM, van Noord PAH, Beijerinck D, et al. Arterial calcification found on breast cancer screening mammograms and cardiovascular mortality in women. The DOM project. Am J Epidemiol 1998;147:333–41. [15] Markopoulos C, Mantas D, Revenas K, et al. Breast arterial calcifications as an indicator of systemic vascular disease. Acta Radiol 2004;45:726–9. [16] American Heart Association Committee Report: a reporting system on patients evaluated for coronary artery disease. Circulation 1975;51:7. [17] Gensini GG. Coronary arteriography. In: Braunwald E, editor. Heart disease. New York: WB Saunders; 1980. p. 308–62. [18] Sullivan DR, Marwick TH, Freedman SB. A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990;119:1262. [19] American College of Radiology. Illustrated breast imaging reporting data system (BI-RADS). Virginia: American College of Radiology; 1998. [20] Everhart JE, Pettitt DJ, Knowler WC, Rose FA, Bennett PH. Medial arterial calcification and its association with mortality and complications of diabetes. Diabetologia 1988;31:16–23. [21] Schmitt EL, Norbeck JM, Threatt B. Incidence of mammary intra-arterial calcification: an age-matched control study. South Med J 1985;78:1440–2. [22] Leinster SJ, Whitehouse GH. Factors which influence the occurrence of vascular calcification in the breast. Br J Radiol 1987;60:457–8. [23] Cox J, Simpson W, Walshaw D. An interesting byproduct of screening: assessing the effect of HRT on arterial calcification in the female breast. J Med Screen 2002;9:38–9. [24] Iribarren C, Go AS, Tolstykh I, et al. Breast vascular calcification and risk of coronary heart disease, stroke and heart failure. J Women’s Health 2004;13:381–9. [25] Henkin Y, Abu-Ful A, Shai I, Crystal P. Lack of association between breast artery calcification seen on mammography and coronary artery disease on angiography. J Med Screen 2003;10:139–42. [26] Witteman JCM, Kok FJ, van Saase JLCM, Valkenburg HA. Aortic calcification as a predictor of cardiovascular mortality. Lancet 1986;2:1120–2. [27] Witteman JCM, Kannel WB, Wolf PA, et al. Aortic calcified plaques and cardiovascular disease (the Framingham Study). Am J Cardiol 1990;66:1060–4.
Relationship between the arterial calcification detected in mammography and coronary artery disease b, ¨ Ugur Topal a,∗ , Aysel Kaderli b , Naile Bolca Topal a , B¨ulent Ozdemir Dilek Yes¸ilbursa b , Jale Cordan b , B¨ulent Ediz c , Ali Aydınlar b a b
Department of Radiology, Uludag University, Medical School, G¨or¨ukle Campus, 16059 Bursa, Turkiye Department of Cardiology, Uludag University, Medical School, G¨or¨ukle Campus, 16059 Bursa, Turkiye c Department of Statistics, Uludag University, Medical School, G¨ or¨ukle Campus, 16059 Bursa, Turkiye Received 16 October 2006; received in revised form 25 January 2007; accepted 26 January 2007
Abstract Objective: Arterial calcification is frequently encountered in mammography. The frequency of breast arterial calcification (BAC) increases with increasing age. Studies have shown that BAC is seen more frequently among the people who are under the risk of coronary artery diseases (CAD) such as diabetes and hypertension. The objective of this study is to investigate the relationship between the arterial calcification detected in mammography and the CAD. Material and methods: Screening mammography was performed in 123 women above the age of 40 years who had been examined with coronary angiography for the evaluation of CAD. The presence of BAC, number of affected vessels, and the distribution of calcification in the vessel wall were evaluated in the mammography. Subjects were questioned in terms of the cardiovasculary risk factors. The severity of CAD was evaluated according to the Gensini scoring. In addition, the number of blood vessels with stenosis of more than 50% was used as the vascular score. The correlation between Gensini and the vascular scores, and BAC was statistically evaluated using Mann–Whitney U and Kruskal–Wallis tests. Results: Eighty (65%) of 123 patients had CAD. BAC was detected in the mammography of 49 (39.8%) subjects. The ages and duration of menopause of the cases with BAC were significantly higher than those without BAC (p < 0.001). There was an almost significant correlation between the BAC and Gensini scores (p = 0.059). There was a significant increase in the frequency of BAC among subjects with more than two vessels with stenosis (p = 0.033). Conclusion: Frequency of BAC increases with increasing age. BAC is also frequently seen in subjects having severe coronary artery disease. Although increasing age may be a factor increasing the frequency of BAC, BAC may also be an indicator of CAD. Therefore, the mentioning of arterial calcification in mammography reports may be important in warning the clinician in terms of CAD. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Arterial calcification; Breast; Mammography; Coronary artery disease
1. Introduction Arterial calcification is a common finding in screening mammography. The frequency of breast arterial calcification (BAC) increases with increasing age and is seen in 9–12% of women above the age of 50 [1,2]. Although BAC is a finding of ageing, it may also emerge as an indicator of diabetes mellitus (DM), hypertension and other vascular diseases [3–5]. BAC is considered to be an independent risk factor for coronary artery disease
∗
Corresponding author. Tel.: +90 224 4428845; fax: +90 224 4428142. E-mail address: [email protected] (U. Topal).
0720-048X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2007.01.035
(CAD) in old age especially for the women with DM [4] and cardiovascular mortality is found to be 40% higher among the patients with BAC [6]. As we already know, calcification is useful in predicting the atherosclerotic plaque burden in the epicardial coronary arteries in the patients with no complaints [7]. There is a strong correlation between the frequencies of coronary artery calcification and cardiovascular diseases [8]. Similar to BAC, the frequency of coronary artery calcification increases with age [9]. Various studies have stated that coronary artery calcification scoring may be a useful predictor of cardiovascular diseases [10,11]. On the other hand, calcification was detected in the aortic wall of 33% of the subjects, who underwent computed tomography exam-
392
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
ination of the thorax for some cause (tuberculosis, malignity, etc.) [12]. Calcification in the aortic wall is shown to be related to age, hypertension, DM, smoking and alcohol consumption, hyperlipidemia, obesity and other vascular diseases [13]. The presence of calcification in the aortic wall in women, and its presence in peripheral arteries in diabetic patients increase the risk of death by 1.5 times [14]. Markopoulos et al., showed that there is a correlation between BAC, detected in mammography, and systemic vascular diseases, and argued that BAC is an indicator of systemic vascular atherosclerosis [15]. Several studies have argued that arterial calcifications may be considered as an indicator of cardiovascular events [4,6,8]. In our study, we aimed to investigate the relationship between BAC, detected in mammography, and coronary atherosclerosis among women above the age of 40 who were examined with coronary angiography. 2. Material and methods One hundred and twenty-three females, aged between 40 and 77 (mean 56.84 ± 9.54), who underwent coronary angiography were included into the study. One hundred and fifteen of the subjects were in their post-menopausal period. The duration of menopause ranged from 3 months to 35 years (mean 10.24 ± 9.08). None of the subjects had history of hormone replacement therapy (HRT). Subjects were evaluated in terms of the risk factors of coronary artery disease (hypertension, DM, hyperlipidemia, obesity, family history, and smoking), heart diseases (heart failure, known coronary artery disease), coronary artery disease equivalents (DM, carotid artery disease, abdominal aortic aneurysm, peripheral artery disease) and any therapies they received. The clinical forms of CAD were classified as stable angina, acute coronary syndrome and previous history of myocardial infarction. Coronary angiography was performed with the Judkins method. Angiography was performed due to the history of myocardial infarction in 15 patients, acute coronary syndrome in 17 patients and the history of chest pain with positive exercise stress test in 91 patients. Angiography images were evaluated by two experienced cardiologists. Evaluation of the coronary atherosclerosis was performed in accordance with the Gensini scoring [16,17]. The severity of stenosis in the lumen of the coronary artery, the particular blood vessels in which stenosis occurred, and their location are all taken into account in the Gensini scoring. According to this, the coronary artery is separated into 15 segments, and coefficients ranging from 0.5 and 5.0 are assigned to each artery (Table 1). Percentages of stenosis are evaluated by giving numbers from 0 to 32. Scoring is performed in accordance with the degree of severity of stenosis. The coefficients that are given according to the localization and percent of stenosis of each lesion are multiplied with each other, and this value is taken as the total score of that particular lesion. Gensini score is obtained by the addition of the total score that is calculated for each coronary stenosis (Table 1). We also calculated the vascular score that is considered to be another predictor of the severity of coronary artery disease [18]. Vascular score was expressed as the number of blood vessels constricted more than
Table 1 Calculation of the Gensini scoring index Score Lumen stenosis (%) <25 26–50 51–75 76–90 91–98 99 100
Coefficient
0 1 2 4 8 16 32
Left main coronary artery
5
Left anterior descending artery Proximal Middle Distal
2.5 1.5 1
First diagonal Second diagonal
1 0.5
Circumflex Proximal Middle Distal
1.5 1 1
Obtus marginal Posterolateral
1 0.5
Right coronary artery Proximal Middle Distal
1 1 1
Posterior descending artery
1
50%. Vascular score was defined as non-critical lesion in the cases with stenosis less than 50%. Subjects were divided into three groups as non-critical, single blood vessel involvement, and multiple (≥2) blood vessel involvement according to their vascular scores. Screening mammography was performed to subjects within 2–10 days after coronary angiography procedure. Permission was obtained from the ethics committee of the hospital. Subjects were informed about the study and its procedures, and an informed consent was obtained from each patient. Mammography examinations were evaluated by an experienced radiologist, who was blinded to the clinical features of the patients, according to the BI-RADS (breast imaging and reporting data system) classification recommended by the American College of Radiology [19]. The presence of arterial calcification, the number of calcified blood vessels, whether one or both breast was involved, and the distribution of calcification in the vessel wall were investigated. The distribution of vascular calcification in the vessel wall was evaluated in terms of its involvement of the entire vessel wall either continuously or discontinuously. If the vessel wall was calcified throughout its length, it was categorized as continuous involvement (Fig. 1). If the whole vessel wall was not calcified and there were interruptions between calcifications, then it was categorized as discontinuous involvement (Fig. 2). In the presence of both continuous and discontinuous involvement of more than one vessel in one breast, it was accepted as continuous involvement.
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
393
The presence of BAC, involvement of one or both breasts, the number of blood vessels involved and the distribution of calcification was compared with the Gensini scores. Statistical analysis was performed by entering the data into SPSS 13.0. Data was presented as means ± standard deviation. Mann–Whitney U and Kruskal–Wallis tests were used in the evaluation. Statistical significance was taken as p < 0.05. 3. Results
Fig. 1. The vessel walls were calcified continuously. Calcifications were seen throughout the vessel wall.
Coronary artery disease has been detected in 80 subjects (65%) out of 123 included in the study. Fifteen of the subjects (12%) had a history of past myocardial infarction, 23 (19%) had a diagnosis of stable angina pectoris, and 17 patients had been diagnosed with acute coronary syndrome. When evaluated in terms of cardiovascular risk factors, 92 (74.8%) had hypertension, 16 (13%) smoked cigarette, and 28 (22.7%) a family history. Average LDL cholesterol level was calculated to be 125.29 ± 34.64. While Gensini scores ranged from 0 to 188, the mean score was 14.79 ± 29.36. In terms of vascular scores, 32 (26%) had a non-critical, 18 (15%) single vessel, and 30 (24%) multiple vessel coronary artery disease (blood vessel score ≥2). According to the mammography examinations, no significant findings of malignancy were determined in any of the cases. BAC was detected in a total of 49 (39.8%) subjects; in one breast in 16 (13%) subjects and in two breasts in 33 (26.8%) subjects. Of the subjects with BAC, 22 (44.9%) had calcifications in one blood vessel, 15 (30.6%) had calcifications in two blood vessels, and 12 (24.5%) had calcification in more than two vessels. Calcifications in the vessel wall were evaluated as discontinuous in 29 (59.2%) subjects, and continuous in 20 (40.8%) cases. Ages and durations of menopause of the subjects who were diagnosed with BAC were higher than those without BAC in a statistically significant manner (p < 0.001). Ages of the cases with BAC ranged from 48 to 77, and the mean value was 63.85 ± 7.16 years. Ages of the subjects who did not have BAC ranged from 40 to 73, and the mean value was 52.34 ± 7.69 years. The average duration of menopause for the group with BAC was 15.60 ± 8.87 years, whereas it was 6.39 ± 7.11 years for the group without BAC. There was no statistically significant difference between the two groups in terms of hypertension, DM, Table 2 Distribution of the demographic features and cardiovascular risk factors of the subjects by the presence of BAC BAC (+) (n = 49) (%)
Fig. 2. The vessel walls were calcified discontinuously. Only some parts of the wall were calcified; there were interruptions between calcifications.
Age (years) Duration of menopause (years) DM Hypertension Smoking Family history LDL (mg/dl) HDL (mg/dl)
BAC (−) (n = 74) (%)
63.85 ± 7.16 15.60 ± 8.87
52.34 ± 7.69 6.39 ± 7.11
16 (33) 40 (82) 3 (6) 22 (44) 131.59 ± 31.10 47.39 ± 9.44
17 (23) 52 (70) 10 (13) 27 (37) 122.28 ± 36.14 47.69 ± 8.36
BAC: breast arterial calcification; NS: not significant.
p <0.001 <0.001
NS NS NS NS NS NS
394
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
Table 3 The relationship between BAC and CAD
Presence of CAD Non-critical Single vessel involvement Multiple vessel involvement Gensini score
BAC (+) (n = 49) (%)
BAC (−) (n = 74) (%)
p
36 (73) 11 (22) 6 (13)
44 (60) 21 (29) 11 (15)
NS NS NS
19 (38)
12 (16)
0.033
17.47 ± 28.13
13.00 ± 30.19
0.059
BAC: breast arterial calcification; CAD: coronary artery disease; NS: not significant.
smoking, family history, and cardiovascular risk factors such as hyperlipidemia (Table 2). When the cases were evaluated in terms of the correlation between the Gensini scoring, which indicates the severity of coronary artery disease, and BAC, an almost statistically significant relationship was established (p = 0.059). The frequency of BAC showed a significant increase in subjects who had a vascular score of 2 or more (p = 0.033) (Table 3). There was no significant correlation between BAC and the clinical presentation of coronary artery disease, and the drug treatment that is performed. There was no correlation between the number of calcified blood vessels detected in mammography, the form of calcification and its distribution, and the Gensini scoring. 4. Discussion Arterial calcifications, which are commonly detected in mammography, develop as a result of extensive calcification of the medial layer (M¨onckeberg’s arteriosclerosis). Medial calcification is a common finding of extremity radiographs and resembles railroad tracks or rings in enface images. It is thought that medial arterial calcification is a result of the aging process and thought as an unimportant finding. However many studies have shown that many elderly male patients having DM, renal insufficiency, hypertension, and familial amyloidosis with polyneuropathy also have calcifications [20]. Baum et al. have suggested that BAC found in mammography might point to clinically undiagnosed cases of DM [3]. Nevertheless, Sickles and Galvin suggested that BAC should be considered more of an indicator of old age than of diabetes [2], since BAC rate for 70-year-old female patients is 28 times higher than that of 50-year-old (1.3% and 36%, respectively). It has been suggested in the succeeding studies that hormonal factors, such as pregnancy and early menopause, as well as age also contribute in the formation of BAC [21,22]. Based on these findings it has been concluded that hormone replacement therapy can undermine the formation of BAC, hence prevent the formation post-menopausal cardiovascular diseases [22,23]. In our series, the rate of BAC also increased with age (Table 2). The average age for BAC was 63.85 ± 7.16 and the average age of the group without BAC was 52.34 ± 7.69. The difference between the two groups was found to be statistically significant (p < 0.001). Another factor that significantly correlated with BAC was the duration of menopause (Table 2).
As the duration of menopause increased, the rate of BAC also increased (Table 2). No statistically significant relationship was found between BAC and cardiovascular risk factors such as hypertension, DM, smoking, family history, and hyperlipidemia. Findings of various studies indicate that BAC can be an independent risk factor for CAD [4,14,24]. Moshyedi et al. stated that BAC correlated strongly with DM and CAD in their study conducted on 182 patients less than 59 years of age who underwent coronary angiography with the suspicion of CAD. However, the abundance of CAD cases in the sample of non-BAC patients under 59 years of age indicates that BAC has a low sensitivity in terms of CAD, which renders it unsuitable to be used as a screening test [4]. The correlation between CAD and BAC decreases with increasing age. In women above the age of 59, CAD is less common in the presence of BAC, regardless of diabetes status. These results suggest that other factors, in addition to old age, are involved in the formation of BAC [4]. Henkin et al. have, however, stated that BAC did not have a significant difference among those with and without the angiographic findings of CAD [25]. Similar findings of correlation of BAC with age related CAD has also been reported in other arterial systems [26]. The calcifications detected in abdominal aorta have been defined as a possible indicator of increased risk of disease in young males [26]. Arterial calcifications become more intense, however less correlated with risk, with increasing age. Similarly, the presence of calcifications in thoracic aorta increases the risk of CAD in males and females under the age of 65 [27]. In our study, Gensini scoring and vascular scoring were both used in evaluating the severity of coronary artery diseases. As seen in Table 1, Gensini scoring is derived by taking into consideration the particular blood vessel in which the atherosclerotic lesion is located, the localization of the lesion in the blood vessel and the lesion’s severity. By using Gensini scoring, vascular stenosis less than 50% were also taken into consideration [16–18]. On the other hand, vascular scoring is a scoring system which considers only the critical lesions. As indicated in Table 3, according to our results, there is an almost significant statistical relationship between the Gensini scoring and BAC (p = 0.059). In subjects with many vessel involvement according to the vascular scoring, BAC frequency shows a statistically significant increase (p = 0.033). Therefore, BAC may be an indicator of severe coronary artery disease in women above 40 years of age. However, as we already know the frequency of both CAD and BAC increases with increasing age, therefore the results may be biased because of the higher mean age of the patients in CAD group. There are some limitations of our study. One of these is that the study has focused on patients suspected to have CAD who underwent coronary angiography. This sample will not be representative of the general population. Another shortcoming is the small size of our sample. So, this study needs to be verified using series with larger sample size. In conclusion, detection of BAC in mammography increases with age and duration of menopause. BAC is also frequent in subjects having severe coronary artery disease. Although increasing age may be a factor increasing the frequency of BAC, BAC may
U. Topal et al. / European Journal of Radiology 63 (2007) 391–395
also be a strong indicator of CAD. Therefore, the mentioning of arterial calcification in mammography reports may be a useful notice for the clinician as a potential indicator of CAD. However, our results should be supported with further studies with larger series. References [1] Schmitt EL, Threatt BA. Mammographic intra-arterial calcifications. J Can Assoc Radiol 1984;35:14–6. [2] Sickles EA, Galvin HB. Breast arterial calcification in association with diabetes mellitus: too weak a correlation to have clinical utility. Radiology 1985;155:577–9. [3] Baum JK, Comstock CH, Joseph L. Intramammary arterial calcifications associated with diabetes. Radiology 1980;136:61–2. [4] Moshyedi AC, Puthawala AH, Kurland RJ, O’Leary DH. Breast arterial calcification: association with coronary artery disease. Radiology 1995;194:181–3. [5] C ¸ etin M, C ¸ etin R, Tamer N. Prevalence of breast arterial calcification in hypertensive patients. Clin Radiol 2004;59:92–5. [6] Kemmeren JM, Beijerinck D, vanNoord PAH, et al. Breast arterial calcifications: association with diabetes mellitus and cardiovascular mortality. Radiology 1996;201:75–8. [7] Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243–52. [8] Hosoi M, Sato T, Yamagami K, et al. Impact of diabetes on coronary stenosis and coronary artery calcification detected by electron-beam computed tomography in symptomatic patients. Diab Care 2002;25:696–701. [9] Allison MA, Wright CM. Age and gender are the strongest clinical correlates of prevalent coronary calcification (R1). Intern J Cardiol 2005;98:325–30. [10] Agaston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1999;15:827–32. [11] Haberl R, Becker A, Leber A, et al. Correlation of coronary calcification and angiographically documented stenosis in patients with suspected coronary artery disease: results on 1764 patients. J Am Coll Cardiol 2001;37:451–7.
395
[12] Itani Y, Watanabe S, Masuda Y. Aortic calcification detected in a mass chest screening program using a mobile helical computed tomography unit. Circ J 2004;68:538–41. [13] Gorich J, Zuna I, Merle M, et al. Aortic calcification in CT: correlation with risk factors and cardiovascular disease. Radiologie 1989;29:614–9. [14] Kemmeren JM, van Noord PAH, Beijerinck D, et al. Arterial calcification found on breast cancer screening mammograms and cardiovascular mortality in women. The DOM project. Am J Epidemiol 1998;147:333–41. [15] Markopoulos C, Mantas D, Revenas K, et al. Breast arterial calcifications as an indicator of systemic vascular disease. Acta Radiol 2004;45:726–9. [16] American Heart Association Committee Report: a reporting system on patients evaluated for coronary artery disease. Circulation 1975;51:7. [17] Gensini GG. Coronary arteriography. In: Braunwald E, editor. Heart disease. New York: WB Saunders; 1980. p. 308–62. [18] Sullivan DR, Marwick TH, Freedman SB. A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990;119:1262. [19] American College of Radiology. Illustrated breast imaging reporting data system (BI-RADS). Virginia: American College of Radiology; 1998. [20] Everhart JE, Pettitt DJ, Knowler WC, Rose FA, Bennett PH. Medial arterial calcification and its association with mortality and complications of diabetes. Diabetologia 1988;31:16–23. [21] Schmitt EL, Norbeck JM, Threatt B. Incidence of mammary intra-arterial calcification: an age-matched control study. South Med J 1985;78:1440–2. [22] Leinster SJ, Whitehouse GH. Factors which influence the occurrence of vascular calcification in the breast. Br J Radiol 1987;60:457–8. [23] Cox J, Simpson W, Walshaw D. An interesting byproduct of screening: assessing the effect of HRT on arterial calcification in the female breast. J Med Screen 2002;9:38–9. [24] Iribarren C, Go AS, Tolstykh I, et al. Breast vascular calcification and risk of coronary heart disease, stroke and heart failure. J Women’s Health 2004;13:381–9. [25] Henkin Y, Abu-Ful A, Shai I, Crystal P. Lack of association between breast artery calcification seen on mammography and coronary artery disease on angiography. J Med Screen 2003;10:139–42. [26] Witteman JCM, Kok FJ, van Saase JLCM, Valkenburg HA. Aortic calcification as a predictor of cardiovascular mortality. Lancet 1986;2:1120–2. [27] Witteman JCM, Kannel WB, Wolf PA, et al. Aortic calcified plaques and cardiovascular disease (the Framingham Study). Am J Cardiol 1990;66:1060–4.