Abstract
OBJECTIVES:
We investigated the relationship between metabolic syndrome and breast arterial calcification detected via mammography in a cohort of postmenopausal subjects.
METHODS:
Among 837 patients referred to our radiology department for mammographic screening, 310 postmenopausal females (105 patients with and 205 patients without breast arterial calcification) aged 40 to 73 (mean 55.9±8.4) years were included in this study. The groups were compared with respect to clinical characteristics and metabolic syndrome criteria. Univariate and multivariate analyses identified the factors related to breast arterial calcification.
RESULTS:
Age, postmenopausal duration and the frequencies of diabetes mellitus, hypertension and metabolic syndrome were significantly higher in the subjects with breast arterial calcification than in those without (p<0.05). Multivariate analysis indicated that age (OR = 1.3, 95% CI = 1.1-1.6, p = 0.001) and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005) were independent predictors of breast arterial calcification detected via mammography. The independent predictors among the features of metabolic syndrome were low levels of high-density lipoproteins (OR = 8.1, 95% CI = 1.0−64.0, p = 0.047) and high blood pressure (OR = 8.7, 95% CI = 1.5−49.7, p = 0.014).
CONCLUSIONS:
The likelihood of mammographic detection of breast arterial calcification increases with age and in the presence of hypertension or metabolic syndrome. For patients undergoing screening mammography who present with breast arterial calcification, the possibility of metabolic syndrome should be considered. These patients should be informed of their cardiovascular risk factors and counseled on appropriate lifestyle changes.
Breast; Mammography; Metabolic Cardiovascular Syndrome
INTRODUCTION
Metabolic syndrome (MS) is a constellation of interrelated cardiovascular risk
factors, including insulin resistance or glucose intolerance, hypertension,
atherogenic dyslipidemia and visceral obesity. Similarly, MS is associated with
prothrombotic and proinflammatory conditions (11. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin
BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart
Association/National Heart, Lung, and Blood Institute Scientific Statement.
Circulation. 2005;112(17):2735-52,
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.169404.
http://dx.doi.org/10.1161/CIRCULATIONAHA...
) as well as with an increased incidence of coronary artery disease
(22. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, et al.
Cardiovascular morbidity and mortality associated with the metabolic syndrome.
Diabetes Care. 2001;24(4):683-9,
http://dx.doi.org/10.2337/diacare.24.4.683.
http://dx.doi.org/10.2337/diacare.24.4.6...
). The prevalence of MS increases with
age, particularly after menopause (33. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome
among US adults: findings from the Third National Health and Nutrition
Examination Survey. JAMA. 2002;287(3):356-9,
http://dx.doi.org/10.1001/jama.287.3.356.
http://dx.doi.org/10.1001/jama.287.3.356...
). Using
the Adult Treatment Panel (ATP) III definition, Spila et al. have revealed an MS
prevalence of 40% in women over the age of 45 (44. Sipila K, Koivistoinen T, Moilanen L, Nieminen T, Reunanen A,
Jula A, et al. Metabolic syndrome and arterial stiffness. The health 2000
survey. Metabolism. 2007;56(3):320-6.).
Current clinical practice guidelines recommend that all women of 40 years and older
should receive mammographic screening for the early detection of breast cancer
(55. Screening for breast cancer: U.S. Preventive Services Task Force
recommendation statement. Ann Intern Med. 2009;151(10):716-26.). Breast arterial calcification (BAC)
is commonly observed on screening mammography. The frequency of BAC increases with
age and, according to previously published studies, varies from 1% to 49% (66. Iribarren C, Molloi S. Breast Arterial Calcification: a New
Marker of Cardiovascular Risk? Curr Cardiovasc Risk Rep. 2013;7(2):126-35,
http://dx.doi.org/10.1007/s12170-013-0290-4.
http://dx.doi.org/10.1007/s12170-013-029...
). BAC is identified as medial calcific
sclerosis of the small- to medium-sized muscular arteries in the breast and is
occasionally reported as benign (77. Schmitt EL, Threatt BA. Mammographic intra-arterial
calcifications. J Can Assoc Radiol. 1984;35(1):14-6.,88. Sickles EA. Breast calcifications: mammographic evaluation.
Radiology. 1986;160(2):289-93,
http://dx.doi.org/10.1148/radiology.160.2.3726103.
http://dx.doi.org/10.1148/radiology.160....
). Several studies have demonstrated
relationships between BAC and coronary artery disease (99. Schnatz PF, Marakovits KA, O′Sullivan DM. The association
of breast arterial calcification and coronary heart disease. Obstet Gynecol.
2011;117(2 Pt 1):233-41,
http://dx.doi.org/10.1097/AOG.0b013e318206c8cb.
http://dx.doi.org/10.1097/AOG.0b013e3182...
,1010. Topal U, Kaderli A, Topal NB, Ozdemir B, Yesilbursa D, Cordan J,
et al. Relationship between the arterial calcification detected in mammography
and coronary artery disease. Eur J Radiol. 2007;63(3):391-5,
http://dx.doi.org/10.1016/j.ejrad.2007.01.035.
http://dx.doi.org/10.1016/j.ejrad.2007.0...
), hypertension
(1111. Cetin M, Cetin R, Tamer N, Kelekci S. Breast arterial
calcifications associated with diabetes and hypertension. J Diabetes
Complications. 2004;18(6):363-6,
http://dx.doi.org/10.1016/j.jdiacomp.2004.04.004.
http://dx.doi.org/10.1016/j.jdiacomp.200...
), diabetes mellitus (DM) (1111. Cetin M, Cetin R, Tamer N, Kelekci S. Breast arterial
calcifications associated with diabetes and hypertension. J Diabetes
Complications. 2004;18(6):363-6,
http://dx.doi.org/10.1016/j.jdiacomp.2004.04.004.
http://dx.doi.org/10.1016/j.jdiacomp.200...
12. Sickles EA, Galvin HB. Breast arterial calcification in
association with diabetes mellitus: too weak a correlation to have clinical
utility. Radiology. 1985;155(3):577-9,
http://dx.doi.org/10.1148/radiology.155.3.4001355.
http://dx.doi.org/10.1148/radiology.155....
13. Kemmeren JM, Beijerinck D, van Noord PA, Banga JD, Deurenberg
JJ, Pameijer FA, et al. Breast arterial calcifications: association with
diabetes mellitus and cardiovascular mortality. Radiology. 1996;201(1):75-8,
http://dx.doi.org/10.1148/radiology.201.1.8816524.
http://dx.doi.org/10.1148/radiology.201....
-1414. Baum JK, Comstock CH, Joseph L. Intramammary arterial
calcifications associated with diabetes. Radiology. 1980;136(1):61-2,
http://dx.doi.org/10.1148/radiology.136.1.7384525.
http://dx.doi.org/10.1148/radiology.136....
)
and carotid intima thickening (1515. Yildiz S, Yildiz A, Ertug N, Kaya I, Yilmaz R, Yuksel E, et al.
Association of breast arterial calcification and carotid intimamedia thickness.
Hear Vessel. 2008;23(6):376-82,
http://dx.doi.org/10.1007/s00380-008-1058-5.
http://dx.doi.org/10.1007/s00380-008-105...
,1616. Sedighi N, Radmard AR, Radmehr A, Hashemi P, Hajizadeh A, Taheri
AP. Breast arterial calcification and risk of carotid atherosclerosis: focusing
on the preferentially affected layer of the vessel wall. Eur J Radiol.
2011;79(2):250-6.). One study has indicated an association
between BAC and MS; however, no study in the literature has investigated a potential
association between BAC and MS among postmenopausal women. Therefore, the objective
of this study was to determine the relationship between BAC detected on mammography
and MS in postmenopausal patients.
MATERIALS AND METHODS
Study population and design
Among 837 consecutive women who had been referred to our radiology department for screening mammography, 310 postmenopausal females aged 40-73 (mean 55.9±8.4) years were included in this prospective study, which was conducted between October 2011 and September 2013. This study was reviewed and approved by our institutional ethics committee. The investigator explained the research to and obtained informed consent from each participant.
The exclusion criteria included premenopausal status; prior breast surgery or the presence of trauma; coronary artery disease; and any history of malignancy, cerebrovascular diseases, or major systemic diseases such as renal insufficiency, liver disease, or connective tissue disease. Of the 310 selected patients, 105 were assigned to the BAC (+) group and 205 to the BAC (-) group. A questionnaire that addressed the patient's medical history, the number of infants she had delivered, the age of the patient and the duration of menopause was administered and a comprehensive physical examination was performed on each participant. The fasting blood glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels, as well as the weight and waist circumference, were measured.
Mammography technique
Each study participant underwent a full-field digital mammographic examination in the bilateral standard, mediolateral oblique and craniocaudal positions (Mammomat Inspiration, Siemens, Erlangen, Germany). The mammographic images were analyzed in accordance with the recommended breast-reporting guidelines of the American College of Radiology by an experienced radiologist (1717. American College of Radiology.Illustrated breast imaging reporting data system (BI-RADS). Virginia: American College of Radiology, 1998.). BAC was characterized by deposits of two parallel lines of calcium distributed along the periphery of the configuration of the tapered structures of the arteries, distinct from the breast ducts (Figure 1).
Right mediolateral oblique mammogram showing arterial wall calcifications in a 65-year-old woman (arrows).
Definition of MS
The National Cholesterol Education Program Adult Treatment Panel III
(NCEP-ATPIII) (11. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin
BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart
Association/National Heart, Lung, and Blood Institute Scientific Statement.
Circulation. 2005;112(17):2735-52,
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.169404.
http://dx.doi.org/10.1161/CIRCULATIONAHA...
) defines MS as follows:
(i) a waist circumference of >102 cm for males and >88 cm for females;
(ii) fasting serum triglycerides ≥150 mg/dL or drug treatment for
elevated triglycerides; (iii) HDL cholesterol <40 mg/dL in males and
<50 mg/dL in females or treatment with drugs for reduced HDL cholesterol;
(iv) high blood pressure, i.e., diastolic blood pressure ≥85 mmHg,
systolic blood pressure ≥130 mmHg, or treatment with drugs for
hypertension; and (v) high glucose levels (fasting serum glucose ≥100
mg/dL or treatment with drugs for elevated glucose levels).
Baseline definitions and measurements
For the purposes of this study, hypertension was defined by systolic blood
pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or
treatment with an antihypertensive drug (1818. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A,
Böhm M, et al. 2013 ESH/ESC Guidelines for the management of arterial
hypertension: The Task Force for the management of arterial hypertension of the
European Society of Hypertension (ESH) and of the European Society of Cardiology
(ESC). J Hypertens. 2013;31(7):1281-357,
http://dx.doi.org/10.1097/01.hjh.0000431740.32696.cc.
http://dx.doi.org/10.1097/01.hjh.0000431...
). The diagnosis of DM was based on a fasting plasma glucose
concentration of ≥126 mg/dL in two measurements or treatment with insulin
or oral glucose-lowering agents. The BMI (kg/m2) was calculated by
dividing each patient's weight (kg) by her height (m2). The
waist circumference of each patient was measured from the midpoint of the line
between the last rib and the crista iliaca, following exhalation and while the
patient was in a standing position.
Statistical analyses
The statistical analyses were performed using version 12 of the Statistical Package for Social Sciences for Windows (SPSS Inc., Chicago, IL, USA). The continuous variables were reported as the mean±SD and the categorical variables were expressed as percentages. An independent Student's t-test for normally distributed data was used to compare each continuous variable between the two patient groups, whereas the categorical variables were compared using Fisher's exact test or the chi-squared test, as appropriate. Pearson's correlation coefficient was used to evaluate the correlations among all variables. Univariate and multivariate analyses were performed for the identification of the factors related to BAC. The statistical tests were all two-sided; a p-value of <0.05 was considered to be statistically significant.
RESULTS
The percentage of BAC (+) individuals among the women referred for mammographic screening was 16.6% (139 of 837 cases). Our study population included 105 patients in the BAC (+) group and 205 in the BAC (-) group. Table 1 presents the clinical, hemodynamic and reproductive characteristics and laboratory parameters of each group.
The ages of the women participating in this study ranged from 40 to 73 years, with an average of 55.9±8.4 years. The mean ages of the BAC (+) and BAC (-) groups were 60.7±9.4 years and 53.4±6.2 years, respectively (p<0.001). The mean postmenopausal periods for the two groups were 9.3±2.6 years and 6.4±1.9, respectively (p = 0.04).
The incidences of hypertension and DM were higher among the BAC (+) subjects than among the BAC (-) subjects (p = 0.016 and p = 0.033, respectively). Systolic blood pressure was higher in the BAC (+) group, in which more childbirths, longer breastfeeding durations, greater BMI scores and larger waist circumferences as well as higher levels of LDL cholesterol, triglycerides and fasting glucose were also reported; however, these differences were not statistically significant. The mean HDL cholesterol levels were significantly lower among the BAC (+) subjects than among the BAC (-) subjects (52.5±15.2 dL vs. 61.3±16.8 dL, respectively; p = 0.049). The BAC (-) group reported significantly higher cigarette consumption than did the BAC (+) group (7.6% and 26.3%, respectively; p = 0.011).
In our study population, the overall prevalence of MS was 31.3%. The prevalence of MS was significantly higher in the BAC (+) group than in the BAC (-) group (61.9% vs. 15.6%, respectively; p<0.001) (Figure 2). In a comparison of the individual parameters constituting MS between the BAC (+) and BAC (-) groups, the BAC (+) was found to contain higher percentages of patients with high fasting blood glucose levels (45.7% and 30.7%, respectively; p = 0.041), low HDL cholesterol levels (21.9% and 9.8%, respectively; p = 0.015) and high blood pressure (59.1% and 34.6%, respectively; p = 0.01). In a comparison of waist circumferences and serum fasting triglyceride levels between the two groups, no statistically significant differences were found (Table 2).
Multivariate analysis
In one multivariate model, age (OR = 1.3, 95% CI = 1.1−1.6, p = 0.001) and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005) were found to be independent predictors of BAC (Table 3). Among the features of MS, low high-density lipoprotein (HDL) levels (OR = 8.1, 95% CI = 1.0−64.0, p = 0.047) and high blood pressure (OR = 8.7, 95% CI = 1.5−49.7, p = 0.014) independently predicted the presence of BAC (Table 2).
In the univariate analyses, cigarette consumption and postmenopausal duration were statistically significant; however, these factors were not determined to be independent predictors for BAC in the multivariate analysis. Classic hypertension (OR = 2.4, 95% CI = 1.2−7.5, p = 0.002) was an independent predictor of BAC (+) patients in a multivariate model that included classic hypertension, DM and HDL cholesterol.
DISCUSSION
The present study represents a unique evaluation of the relationship between BAC and MS in postmenopausal women. Our results indicate that the detection of BAC via mammography is associated with MS in a relationship that is apparently independent of age.
Breast arterial calcification, which is occasionally reported as benign, develops as
a result of extensive calcification of the small- to medium-sized muscular arteries
in the breast and is commonly found on mammograms (77. Schmitt EL, Threatt BA. Mammographic intra-arterial
calcifications. J Can Assoc Radiol. 1984;35(1):14-6.,88. Sickles EA. Breast calcifications: mammographic evaluation.
Radiology. 1986;160(2):289-93,
http://dx.doi.org/10.1148/radiology.160.2.3726103.
http://dx.doi.org/10.1148/radiology.160....
). The reported frequency of
BAC detected via mammography in previously published studies varies from 1% to 49%
(66. Iribarren C, Molloi S. Breast Arterial Calcification: a New
Marker of Cardiovascular Risk? Curr Cardiovasc Risk Rep. 2013;7(2):126-35,
http://dx.doi.org/10.1007/s12170-013-0290-4.
http://dx.doi.org/10.1007/s12170-013-029...
); our study indicates a 16.6%
prevalence rate.
Associations between BAC detected via mammography and reproductive factors such as
the duration of breastfeeding, the number of infant deliveries, early menopause and
the duration of menopause have previously been reported (1919. Maas AH, van der Schouw YT, Beijerinck D, Deurenberg JJ, Mali
WP, van der Graaf Y. Arterial calcifications seen on mammograms: cardiovascular
risk factors, pregnancy, and lactation. Radiology. 2006;240(1):33-8,
http://dx.doi.org/10.1148/radiol.2401050170.
http://dx.doi.org/10.1148/radiol.2401050...
20. Prentice A. Maternal calcium metabolism and bone mineral status.
Am J Clin Nutr. 2000;71(5 Suppl):1312S-6S.-2121. Schnatz PF, Rotter MA, Hadley S, Currier AA, O′Sullivan
DM. Hormonal therapy is associated with a lower prevalence of breast arterial
calcification on mammography. Maturitas. 2007;57(2):154-60,
http://dx.doi.org/10.1016/j.maturitas.2006.12.002.
http://dx.doi.org/10.1016/j.maturitas.20...
). In these
studies, hormonal changes during pregnancy and milk production during lactation were
considered to be determinants of BAC formation. In our study, the number of infant
deliveries and the duration of breastfeeding were higher in the BAC (+) group
than in the BAC (-) group, but the differences were not statistically significant.
Although the duration of menopause was longer in the BAC (+) group, this factor
was not found to be an independent predictor of BAC.
A relationship has been established between age and medial arterial calcification
(66. Iribarren C, Molloi S. Breast Arterial Calcification: a New
Marker of Cardiovascular Risk? Curr Cardiovasc Risk Rep. 2013;7(2):126-35,
http://dx.doi.org/10.1007/s12170-013-0290-4.
http://dx.doi.org/10.1007/s12170-013-029...
). In our study, the rate of BAC was
also observed to increase significantly with age.
Several studies have demonstrated relationships between BAC and coronary artery
disease (99. Schnatz PF, Marakovits KA, O′Sullivan DM. The association
of breast arterial calcification and coronary heart disease. Obstet Gynecol.
2011;117(2 Pt 1):233-41,
http://dx.doi.org/10.1097/AOG.0b013e318206c8cb.
http://dx.doi.org/10.1097/AOG.0b013e3182...
,1010. Topal U, Kaderli A, Topal NB, Ozdemir B, Yesilbursa D, Cordan J,
et al. Relationship between the arterial calcification detected in mammography
and coronary artery disease. Eur J Radiol. 2007;63(3):391-5,
http://dx.doi.org/10.1016/j.ejrad.2007.01.035.
http://dx.doi.org/10.1016/j.ejrad.2007.0...
) and between BAC and cardiovascular risk factors such as hypertension
(1111. Cetin M, Cetin R, Tamer N, Kelekci S. Breast arterial
calcifications associated with diabetes and hypertension. J Diabetes
Complications. 2004;18(6):363-6,
http://dx.doi.org/10.1016/j.jdiacomp.2004.04.004.
http://dx.doi.org/10.1016/j.jdiacomp.200...
), DM (1111. Cetin M, Cetin R, Tamer N, Kelekci S. Breast arterial
calcifications associated with diabetes and hypertension. J Diabetes
Complications. 2004;18(6):363-6,
http://dx.doi.org/10.1016/j.jdiacomp.2004.04.004.
http://dx.doi.org/10.1016/j.jdiacomp.200...
12. Sickles EA, Galvin HB. Breast arterial calcification in
association with diabetes mellitus: too weak a correlation to have clinical
utility. Radiology. 1985;155(3):577-9,
http://dx.doi.org/10.1148/radiology.155.3.4001355.
http://dx.doi.org/10.1148/radiology.155....
13. Kemmeren JM, Beijerinck D, van Noord PA, Banga JD, Deurenberg
JJ, Pameijer FA, et al. Breast arterial calcifications: association with
diabetes mellitus and cardiovascular mortality. Radiology. 1996;201(1):75-8,
http://dx.doi.org/10.1148/radiology.201.1.8816524.
http://dx.doi.org/10.1148/radiology.201....
-1414. Baum JK, Comstock CH, Joseph L. Intramammary arterial
calcifications associated with diabetes. Radiology. 1980;136(1):61-2,
http://dx.doi.org/10.1148/radiology.136.1.7384525.
http://dx.doi.org/10.1148/radiology.136....
), biochemical findings
(2222. Pidal D, Sanchez Vidal MT, Rodriguez JC, Corte MD, Pravia P,
Guinea O, et al. Relationship between arterial vascular calcifications seen on
screening mammograms and biochemical markers of endothelial injury.
Eur J Radiol. 2009;69(1):87-92.) such as hypertriglyceridemia and
high levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) and the
body mass index (2323. van Noord PA, Beijerinck D, Kemmeren JM, van der Graaf Y.
Mammograms may convey more than breast cancer risk: breast arterial
calcification and arteriosclerotic related diseases in women of the DOM cohort.
Eur J Cancer Prev. 1996;5(6):483-7.). Although both
conventional DM and hypertension were more prevalent in our BAC (+) group, only
hypertension was found to be an independent predictor of BAC in our study. Smoking,
despite its established relationship with coronary artery disease, was more
prevalent in the BAC (-) patients; however, according to the multivariate analysis,
smoking was not an independent risk factor. The inverse association between smoking
and BAC observed in the present study is consistent with previous reports (2424. Iribarren C, Go AS, Tolstykh I, Sidney S, Johnston SC, Spring
DB. Breast vascular calcification and risk of coronary heart disease, stroke,
and heart failure. J Womens Health. 2004;13(4):381-9,
http://dx.doi.org/10.1089/154099904323087060.
http://dx.doi.org/10.1089/15409990432308...
,2525. Kataoka M, Warren R, Luben R, Camus J, Denton E, Sala E, et al.
How predictive is breast arterial calcification of cardiovascular disease and
risk factors when found at screening mammography?
Am J Roentgenol. 2006;187(1):73-80.).
Although cardiovascular risk factors are associated with both coronary artery disease
and BAC, studies of the development of BAC have indicated that different basic
factors play the more important role in the pathogenesis of BAC. Whereas
atherosclerosis results in marked intimal calcification of the coronary arteries,
calcification of the tunica media is more predominant in BAC (2626. Nielsen B, Holm N. Calcification in breast arteries. The
frequency and severity of arterial calcification in female breast tissue without
malignant changes. Acta Pathol Microbiol Immunol Scand.
1986;93(1):13-6.). Inflammation, lipid storage and vascular smooth muscle
cells play an active role in intimal calcification; however, in medial
calcification, macrophage and lipid accumulation is not evident (2727. Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL,
Edmonds ME. Medial localization of mineralization-regulating proteins in
association with Monckeberg's sclerosis: evidence for smooth muscle
cell-mediated vascular calcification. Circulation. 1999;100(21):2168-76,
http://dx.doi.org/10.1161/01.CIR.100.21.2168.
http://dx.doi.org/10.1161/01.CIR.100.21....
,2828. Farzaneh-Far A, Proudfoot D, Shanahan C, Weissberg PL. Vascular
and valvar calcification: recent advances. Heart. 2001;85(1):13-7,
http://dx.doi.org/10.1136/heart.85.1.13.
http://dx.doi.org/10.1136/heart.85.1.13...
).
At present, it is impossible to definitively distinguish between intimal and medial
calcification using digital mammography.
Patients with coronary artery disease were excluded from the present study because
several prior studies have already investigated the relationship between coronary
artery disease and BAC (99. Schnatz PF, Marakovits KA, O′Sullivan DM. The association
of breast arterial calcification and coronary heart disease. Obstet Gynecol.
2011;117(2 Pt 1):233-41,
http://dx.doi.org/10.1097/AOG.0b013e318206c8cb.
http://dx.doi.org/10.1097/AOG.0b013e3182...
,1010. Topal U, Kaderli A, Topal NB, Ozdemir B, Yesilbursa D, Cordan J,
et al. Relationship between the arterial calcification detected in mammography
and coronary artery disease. Eur J Radiol. 2007;63(3):391-5,
http://dx.doi.org/10.1016/j.ejrad.2007.01.035.
http://dx.doi.org/10.1016/j.ejrad.2007.0...
,2929. 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(3):139-42,
http://dx.doi.org/10.1258/096914103769011049.
http://dx.doi.org/10.1258/09691410376901...
).
In a meta-analysis of 927 patients, the incidence of coronary artery disease
diagnosed via angiography was found to be higher in patients with BAC (+)
mammograms (3030. AbiRafeh N, Castellanos MR, Khoueiry G, Meghani M, El-Sayegh S,
Wetz RV, et al. Association between coronary artery disease diagnosed by
coronary angiography and breast arterial calcifications on mammography:
meta-analysis of the data. J Womens Health (Larchmt). 2012;21(10):1053-8,
http://dx.doi.org/10.1089/jwh.2011.3388.
http://dx.doi.org/10.1089/jwh.2011.3388...
). Another study demonstrated
no independent relationship between BAC and coronary artery disease diagnosed via
angiography (2929. 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(3):139-42,
http://dx.doi.org/10.1258/096914103769011049.
http://dx.doi.org/10.1258/09691410376901...
). In that study, patients
with significant coronary artery disease were compared with patients with normal
coronary arteries. Patients with non-significant coronary artery disease, however,
were not included in the study, which might explain the discrepancy.
Carotid intima-media thickness is a well-known marker of early atherosclerotic
disease. Two independent studies have demonstrated that BAC is associated with
carotid intima-media thickness independent of age; reproductive factors, such as
parity and postmenopausal duration; and cardiovascular risk factors, including
diabetes, systolic blood pressure, fasting glucose levels and triglyceride levels
(1515. Yildiz S, Yildiz A, Ertug N, Kaya I, Yilmaz R, Yuksel E, et al.
Association of breast arterial calcification and carotid intimamedia thickness.
Hear Vessel. 2008;23(6):376-82,
http://dx.doi.org/10.1007/s00380-008-1058-5.
http://dx.doi.org/10.1007/s00380-008-105...
,1616. Sedighi N, Radmard AR, Radmehr A, Hashemi P, Hajizadeh A, Taheri
AP. Breast arterial calcification and risk of carotid atherosclerosis: focusing
on the preferentially affected layer of the vessel wall. Eur J Radiol.
2011;79(2):250-6.).
Metabolic syndrome is associated with an increased risk of coronary artery disease.
MS results from a combination of cardiovascular risk factors, including high blood
pressure, insulin resistance or glucose intolerance, visceral obesity and
atherogenic dyslipidemia (11. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin
BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart
Association/National Heart, Lung, and Blood Institute Scientific Statement.
Circulation. 2005;112(17):2735-52,
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.169404.
http://dx.doi.org/10.1161/CIRCULATIONAHA...
,22. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, et al.
Cardiovascular morbidity and mortality associated with the metabolic syndrome.
Diabetes Care. 2001;24(4):683-9,
http://dx.doi.org/10.2337/diacare.24.4.683.
http://dx.doi.org/10.2337/diacare.24.4.6...
). The prevalence of MS increases with age,
particularly after menopause. In a study of patients of over 45 years in age, the
prevalence of MS was reported to be as high as 40% (33. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome
among US adults: findings from the Third National Health and Nutrition
Examination Survey. JAMA. 2002;287(3):356-9,
http://dx.doi.org/10.1001/jama.287.3.356.
http://dx.doi.org/10.1001/jama.287.3.356...
,44. Sipila K, Koivistoinen T, Moilanen L, Nieminen T, Reunanen A,
Jula A, et al. Metabolic syndrome and arterial stiffness. The health 2000
survey. Metabolism. 2007;56(3):320-6.). Although several clinical
studies have investigated the relationships between BAC and cardiovascular risk
factors, coronary artery disease, other vascular diseases and reproductive factors,
only one study has explored the relationship between MS and BAC. This study found
that the incidences of diabetes and MS were higher in the BAC (+) group than in
the BAC (-) group (3131. Bae MJ1, Lee SY, Kim YJ, Lee JG, Jeong DW, Yi YH, et al.
Association of breast arterial calcifications, metabolic syndrome, and the
10-year coronary heart disease risk: a cross-sectional case-control study.
J Womens Health (Larchmt). 2013;22 (7):625-30,
http://dx.doi.org/10.1089/jwh.2012.4148.
http://dx.doi.org/10.1089/jwh.2012.4148...
). It also demonstrated
that MS was the only independent predictor of BAC. In our study, a significant
association was found between BAC and MS, independent of age, smoking and
postmenopausal duration. When the parameters constituting MS were examined
individually, independent of age, low HDL cholesterol levels and high blood pressure
were found to be accurate predictors for BAC. One limitation of the present study is
that it was performed in a local region and therefore, the sample may not be
representative of the general population. Because the relationship between MS and
coronary artery disease has been well established (22. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, et al.
Cardiovascular morbidity and mortality associated with the metabolic syndrome.
Diabetes Care. 2001;24(4):683-9,
http://dx.doi.org/10.2337/diacare.24.4.683.
http://dx.doi.org/10.2337/diacare.24.4.6...
), efforts were made to exclude patients with known coronary artery
disease from the study. Second, asymptomatic patients with coronary artery disease
could not be effectively excluded and therefore, some of the patients diagnosed with
MS might have had asymptomatic coronary artery disease. Third, a relatively small
number of BAC (+) patients were included in this study; hence, additional
large-scale trials are required to confirm our findings.
In conclusion, the likelihood of the detection of BAC on mammography increases with age as well as in the presence of hypertension and MS. In BAC (+) screening mammography patients, the possibility of MS should be considered because BAC is closely associated with coronary artery disease and cardiovascular risk factors. Based on the results of this study, we recommend that patients with BAC should be informed of their cardiovascular risk factors and encouraged to consider appropriate lifestyle changes.
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No potential conflict of interest was reported.
Publication Dates
-
Publication in this collection
2014
History
-
Received
2 July 2014 -
Reviewed
23 Sept 2014 -
Accepted
23 Sept 2014