- Email: [email protected]
Breast artery calcium on routine mammography as a potential marker for increased risk of cardiovascular disease
There were several limitations in this study. The use of chart review rather than prospective data collection introduced both a recording and reporting error. In addition, detailed history regarding failure of prior attempted use of aspirin and possible intolerance typically was not recorded in admission histories. We assumed that nonuse of aspirin by patients with a reported history of reflux or ulcer disease was the explanation for deferral, although this presumes a causal relation. This study demonstrates a deficiency in aspirin use for primary prevention in a group of persons with multiple cardiac risk factors admitted with AMI. The risk of aspirin use is unlikely to outweigh its benefit in decreasing cardiovascular morbidity and mortality. 1. Fuster V, Chesebro JH. Aspirin for primary prevention of coronary disease. Eur Heart J 1995;16:(suppl E):16 –20. 2. Cairns J, Theroux P, Lewis D, Ezekowitz M, Meade T, Sutton G. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the Physicians’ Health Study. N Engl J Med 1989;321: 129 –135. 3. ISIS-2 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349 –359. 4. Seneviratne SL, Gunatilake SB, Adhikari AA, Gunawadhana P, de Silva HJ. Changing prescribing behavior: early low dose aspirin in suspected acute myocardial infarction. Int J Cardiol 1998;67:237–240. 5. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and
stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81–106. 6. Fifth ACCP consensus conference on anti-thrombotic therapy. Chest 1998; 114:612S-633S. 7. Pendergrass P, DiGuiseppi C. Aspirin prophylaxis for the primary prevention of myocardial infarction. In: Guide to Preventive Services: Report of the U. S. Preventive Services Task Force. Baltimore: Williams & Wilkens, 1996:845– 851. 8. Hennekens C, Dyken M, Fuster V. AHA scientific statement: aspirin as a therapeutic agent in cardiovascular disease. Circulation 1997;96:2751–2753. 9. He J, Whelton P, Vu B, Klag M. Aspirin, and risk of hemorrhagic stroke. JAMA 1998;280:1930 –1934. 10. Hansson L, Zanchetti A, Carruthers G, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn K, Wedel H, Westerling S. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment randomised trial. Lancet 1998;351:1755– 1762. 11. Manson JE, Stampfer MJ, Colditz GA, Willett W, Rosner B, Speizer F, Hennekens C. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. JAMA 1991;266:521–527. 12. The Medical Research Council’s General Practice Research Framework. Thrombosis Prevention Trial. Randomized trial of low intensity oral anticoagulation with warfarin and low dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet 1998;351:233–241. 13. Stalnikowicz-Darvasi R. Gastrointestinal bleeding during low-dose aspirin administration for the prevention for arterial occlusive events. A critical analysis. J Clin Gastroenterol 1995;21:13–16. 14. Aspirin Myocardial Infarction Study Research Group. A randomized, controlled trial of aspirin in patients recovered from myocardial infarction. JAMA 1980;243:661– 669. 15. Insull W. The problem of compliance to cholesterol altering therapy. J Intern Med 1996;24:317–325. 16. Lane DS, Polendak AP, Burg MA. Effect of continuing medical education and cost reduction on physician compliance with mammography screening guidelines. J Fam Pract 1991;33:359 –368. 17. Holt WS Jr. Factors affecting compliance with screening sigmoidoscopy. J Fam Pract 1991;32:585–589. 18. Fix KN, Oberman A. Barriers to following ACEP guidelines: appraisal of poor physician compliance. Arch Intern Med 1992;152:2385–2387.
Breast Artery Calcium on Routine Mammography as a Potential Marker for Increased Risk of Cardiovascular Disease Pavel Crystal,
MD,
Eugene Crystal, MD, Jonathan Leor, MD, Michael Friger, George Katzinovitch, MD, and Selwyn Strano, MD
awareness about breast cancer and greater compliance in screening programs has resulted in Ithencreased increase of the absolute number of women undergoing mammography. This screening tool for early detection of breast cancer is recommended annually for all women beginning at age 40 years,1 which has been found to be the age when the risk of cardiovascular disorders becomes significant.2 Thus, it seems very attractive to take advantage of this already routine screening tool to detect mammographic signs of atherosclerosis. Breast artery calcium (BAC) was indeed proposed as a marker for increased risk of cardiovascular morbidity and mortality.3,4 However, this study was based on mammograms performed ⬎20 From the Comprehensive Breast Center, Cardiology Department, Soroka Medical Center Department of Epidemiology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva; and Rachel Nash Comprehensive Breast Center, Jerusalem, Israel. Dr. Crystal’s address is: Cardiology Department, Soroka Medical Center, Beer Sheva, Israel. E-mail: [email protected]. Manuscript received October 22, 1999; revised manuscript received and accepted January 31, 2000.
216
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 July 15, 2000
PhD,
years previously. The increased resolution of modern mammography has improved the visibility of microcalcifications, with possible detection of size ⬍100 m in diameter.5,6 Consequently, detection of BAC is better. The objective of our study was to estimate the value of BAC, detected on state of the art equipment as a marker for women at particular cardiovascular risk. •••
Eight hundred sixty-five consecutive women referred for mammography were asked to complete a questionnaire assessing major risk factors for atherosclerosis (age, hypertension, smoking, diabetes mellitus, family history of atherosclerotic cardiovascular disease [ASCVD], dyslipidemia, and menopause). A history of ASCVD (angina pectoris, previous myocardial infarction, abnormal coronary angiography, coronary bypass surgery, or stroke) was also obtained. The mammograms were obtained on 2 mammography units (GE 600 HF, General Electric Medical Systems, Milwaukee, Wisconsin or Gloria, Elscint Inc., Haifa, 0002-9149/00/$–see front matter PII S0002-9149(00)00860-2
TABLE I Prevalence of Main Risk Factors and Cardiovascular Morbidity in BAC-Positive and BAC-Negative Subgroups
Mean age (yrs ⫾ SD) Systemic hypertension Family history for ASCVD Smoking, current and previous Dyslipidemia Diabetes mellitus Menopause Angina pectoris History of myocardial infarction Abnormal coronary angiography Coronary bypass surgery Stroke
BAC Positive (n ⫽ 152)
BAC Negative (n ⫽ 713)
p Value
65 ⫾ 8 79 (52%)
54 ⫾ 9 177 (25%)
⬍0.0001 ⬍0.0001
43 (28%)
288 (40%)
0.007
14 (9%)
212 (30%)
⬍0.0001
180 38 484 36 24
0.02 0.005 ⬍0.0001 ⬍0.0001 0.008
53 18 138 23 13
(35%) (13%) (91%) (15%) (9%)
(25%) (5%) (68%) (5%) (3%)
TABLE II Results of Multiple Logistic Regression Analysis of Risk Factors and BAC for ASCVD Variable
10 (7%)
11 (2%)
0.0007
9 (6%)
17 (2%)
0.04
8 (5%)
8 (1%)
0.002
Israel). The mammograms were analyzed independently for the presence of BAC by 2 experienced mammographers (PC, SS), who were blinded to the results of the questionnaire. BAC was defined as a presence of linear calcium deposit along the periphery of tapered structures whose configuration was typical of arteries, distinct from breast ducts.7 We interpreted the mammography as BAC-positive if the BAC was found on 1 of the 2 standard views in the right or left breast, or both of them.8 The association between BAC and the above-mentioned risk factors and ASCVD was examined. The variables studied in the BAC-positive and BAC-negative subgroups are presented in Table I. The BAC-positive group appears to be older, and the presence of 4 of 6 analyzed major risk factors was notably greater in this population. BAC was associated with near-twofold increase in the existence of ASCVD or ⱖ2 major risk factors (42% vs 23%, p ⬍0.001). Logistic regression analysis was performed to determine the independent association of the studied variables on ASCVD occurrence. The results are presented in Table II. The presence of BAC appeared to be closely associated with the presence of ASCVD, second only in significance to family history. BAC was clearly more strongly significant when compared with all other analyzed risk factors. •••
The reported prevalence of BAC in our study is considerably higher than previously reported (17% vs ⬃8%).3,7–10 This may be partly explained by the enhanced sensitivity of modern mammography. Also, in our study population, there is a greater prevalence of
BAC Age Systemic hypertension Family history of ASCVD Smoking, current and previous Dyslipidemia Diabetes mellitus Menopause
Odds Ratio CI (95%) 2.11 1.06 1.15 3.38 1.04 0.98 1.11 1.08
p Value
1.22–3.66 0.008 1.03–1.10 ⬍0.001 0.93–1.43 0.2 2.05–5.57 ⬍0.001 0.59–1.84 0.892 0.93–1.04 0.579 1.01–1.21 0.035 1.02–1.15 0.007
CI ⫽ confidence interval.
risk factors such as diabetes that can affect prevalence of BAC.9 The significant parallelism of the presence of BAC and most of the major risk factors is striking. The impressively higher cardiovascular morbidity, found in the subgroup of BAC-positive women in our study confirmed this relation. The negative association between BAC and smoking is unexpected but consistent with the finding of Kemmeren et al.4 The major limitation of our study is a potential bias of risk factor data obtained by questionnaire rather than direct and objective measurement. Our findings suggest that BAC may be a practical and inexpensive screening tool for the detection of cardiovascular risk in women. The existence of BAC on mammography may be a useful marker of women at higher risk for ASCVD or with unrecognized heart disease. 1. Feig SA, D’Orsi CJ, Hendrick RE, Jackson VP, Kopans DB, Monsees B. American College of Radiology guidelines for breast cancer screening. Am J Roentgenol 1998;171:29 –33. 2. Eaker ED, Chesebro JH, Sacks FM, Wenger NK, Whisnant JP, Winston M. Cardiovascular disease in women. Circulation 1993;88:1999 –2009. 3. 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;5:483– 487. 4. Kemmeren JM, van Noord PA, Beijerinck D, Fracheboud J, Banga J, van der Graaf Y. Arterial calcifications found on breast cancer screening mammograms and cardiovascular mortality in women. The DOM Project. Am J Epidemiol 1998;147:333–341. 5. Cowen AR, Launders JH, Jadav M, Brettle DS. Visibility of microcalcifications in computed and screen-film mammography. Phys Med Biol 1997;42:1533– 1548. 6. Shaw CC, Wang T, King JL, Breitenstein DS, Chang TS, Harris KM, Baratz AB, Ganott MA, Reginella R, Simkin JH, Gur D. Computed radiography versus screen-film mammography in detection of simulated microcalcifications: a receiver operating characteristic study based on phantom images. Acad Radiol 1998;5:173–180. 7. Leinster SJ, Whitehouse GH. Factors which influence the occurrence of vascular calcification in breast. Br J Radiol 1987;60:457– 458. 8. Kemmeren JM, Beijerinck D, van Noord PA, Banga J, Deurenberg JM, Pameijer FA, Graaf Y. Breast arterial calcifications. Association with diabetes mellitus and cardiovascular mortality. Radiology 1996;201:75–78. 9. Baum JK, Comstock CH, Joseph L. Intramammary arterial calcifications associated with diabetes. Radiology 1980;136:61– 62. 10. Shmitt EL, Norbeck JM, Threatt B. Incidence of mammary intraarterial calcification: an age-matched control study. South Med J 1985;78:1440 –1442.
BRIEF REPORTS
217
stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81–106. 6. Fifth ACCP consensus conference on anti-thrombotic therapy. Chest 1998; 114:612S-633S. 7. Pendergrass P, DiGuiseppi C. Aspirin prophylaxis for the primary prevention of myocardial infarction. In: Guide to Preventive Services: Report of the U. S. Preventive Services Task Force. Baltimore: Williams & Wilkens, 1996:845– 851. 8. Hennekens C, Dyken M, Fuster V. AHA scientific statement: aspirin as a therapeutic agent in cardiovascular disease. Circulation 1997;96:2751–2753. 9. He J, Whelton P, Vu B, Klag M. Aspirin, and risk of hemorrhagic stroke. JAMA 1998;280:1930 –1934. 10. Hansson L, Zanchetti A, Carruthers G, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn K, Wedel H, Westerling S. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment randomised trial. Lancet 1998;351:1755– 1762. 11. Manson JE, Stampfer MJ, Colditz GA, Willett W, Rosner B, Speizer F, Hennekens C. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. JAMA 1991;266:521–527. 12. The Medical Research Council’s General Practice Research Framework. Thrombosis Prevention Trial. Randomized trial of low intensity oral anticoagulation with warfarin and low dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet 1998;351:233–241. 13. Stalnikowicz-Darvasi R. Gastrointestinal bleeding during low-dose aspirin administration for the prevention for arterial occlusive events. A critical analysis. J Clin Gastroenterol 1995;21:13–16. 14. Aspirin Myocardial Infarction Study Research Group. A randomized, controlled trial of aspirin in patients recovered from myocardial infarction. JAMA 1980;243:661– 669. 15. Insull W. The problem of compliance to cholesterol altering therapy. J Intern Med 1996;24:317–325. 16. Lane DS, Polendak AP, Burg MA. Effect of continuing medical education and cost reduction on physician compliance with mammography screening guidelines. J Fam Pract 1991;33:359 –368. 17. Holt WS Jr. Factors affecting compliance with screening sigmoidoscopy. J Fam Pract 1991;32:585–589. 18. Fix KN, Oberman A. Barriers to following ACEP guidelines: appraisal of poor physician compliance. Arch Intern Med 1992;152:2385–2387.
Breast Artery Calcium on Routine Mammography as a Potential Marker for Increased Risk of Cardiovascular Disease Pavel Crystal,
MD,
Eugene Crystal, MD, Jonathan Leor, MD, Michael Friger, George Katzinovitch, MD, and Selwyn Strano, MD
awareness about breast cancer and greater compliance in screening programs has resulted in Ithencreased increase of the absolute number of women undergoing mammography. This screening tool for early detection of breast cancer is recommended annually for all women beginning at age 40 years,1 which has been found to be the age when the risk of cardiovascular disorders becomes significant.2 Thus, it seems very attractive to take advantage of this already routine screening tool to detect mammographic signs of atherosclerosis. Breast artery calcium (BAC) was indeed proposed as a marker for increased risk of cardiovascular morbidity and mortality.3,4 However, this study was based on mammograms performed ⬎20 From the Comprehensive Breast Center, Cardiology Department, Soroka Medical Center Department of Epidemiology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva; and Rachel Nash Comprehensive Breast Center, Jerusalem, Israel. Dr. Crystal’s address is: Cardiology Department, Soroka Medical Center, Beer Sheva, Israel. E-mail: [email protected]. Manuscript received October 22, 1999; revised manuscript received and accepted January 31, 2000.
216
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 July 15, 2000
PhD,
years previously. The increased resolution of modern mammography has improved the visibility of microcalcifications, with possible detection of size ⬍100 m in diameter.5,6 Consequently, detection of BAC is better. The objective of our study was to estimate the value of BAC, detected on state of the art equipment as a marker for women at particular cardiovascular risk. •••
Eight hundred sixty-five consecutive women referred for mammography were asked to complete a questionnaire assessing major risk factors for atherosclerosis (age, hypertension, smoking, diabetes mellitus, family history of atherosclerotic cardiovascular disease [ASCVD], dyslipidemia, and menopause). A history of ASCVD (angina pectoris, previous myocardial infarction, abnormal coronary angiography, coronary bypass surgery, or stroke) was also obtained. The mammograms were obtained on 2 mammography units (GE 600 HF, General Electric Medical Systems, Milwaukee, Wisconsin or Gloria, Elscint Inc., Haifa, 0002-9149/00/$–see front matter PII S0002-9149(00)00860-2
TABLE I Prevalence of Main Risk Factors and Cardiovascular Morbidity in BAC-Positive and BAC-Negative Subgroups
Mean age (yrs ⫾ SD) Systemic hypertension Family history for ASCVD Smoking, current and previous Dyslipidemia Diabetes mellitus Menopause Angina pectoris History of myocardial infarction Abnormal coronary angiography Coronary bypass surgery Stroke
BAC Positive (n ⫽ 152)
BAC Negative (n ⫽ 713)
p Value
65 ⫾ 8 79 (52%)
54 ⫾ 9 177 (25%)
⬍0.0001 ⬍0.0001
43 (28%)
288 (40%)
0.007
14 (9%)
212 (30%)
⬍0.0001
180 38 484 36 24
0.02 0.005 ⬍0.0001 ⬍0.0001 0.008
53 18 138 23 13
(35%) (13%) (91%) (15%) (9%)
(25%) (5%) (68%) (5%) (3%)
TABLE II Results of Multiple Logistic Regression Analysis of Risk Factors and BAC for ASCVD Variable
10 (7%)
11 (2%)
0.0007
9 (6%)
17 (2%)
0.04
8 (5%)
8 (1%)
0.002
Israel). The mammograms were analyzed independently for the presence of BAC by 2 experienced mammographers (PC, SS), who were blinded to the results of the questionnaire. BAC was defined as a presence of linear calcium deposit along the periphery of tapered structures whose configuration was typical of arteries, distinct from breast ducts.7 We interpreted the mammography as BAC-positive if the BAC was found on 1 of the 2 standard views in the right or left breast, or both of them.8 The association between BAC and the above-mentioned risk factors and ASCVD was examined. The variables studied in the BAC-positive and BAC-negative subgroups are presented in Table I. The BAC-positive group appears to be older, and the presence of 4 of 6 analyzed major risk factors was notably greater in this population. BAC was associated with near-twofold increase in the existence of ASCVD or ⱖ2 major risk factors (42% vs 23%, p ⬍0.001). Logistic regression analysis was performed to determine the independent association of the studied variables on ASCVD occurrence. The results are presented in Table II. The presence of BAC appeared to be closely associated with the presence of ASCVD, second only in significance to family history. BAC was clearly more strongly significant when compared with all other analyzed risk factors. •••
The reported prevalence of BAC in our study is considerably higher than previously reported (17% vs ⬃8%).3,7–10 This may be partly explained by the enhanced sensitivity of modern mammography. Also, in our study population, there is a greater prevalence of
BAC Age Systemic hypertension Family history of ASCVD Smoking, current and previous Dyslipidemia Diabetes mellitus Menopause
Odds Ratio CI (95%) 2.11 1.06 1.15 3.38 1.04 0.98 1.11 1.08
p Value
1.22–3.66 0.008 1.03–1.10 ⬍0.001 0.93–1.43 0.2 2.05–5.57 ⬍0.001 0.59–1.84 0.892 0.93–1.04 0.579 1.01–1.21 0.035 1.02–1.15 0.007
CI ⫽ confidence interval.
risk factors such as diabetes that can affect prevalence of BAC.9 The significant parallelism of the presence of BAC and most of the major risk factors is striking. The impressively higher cardiovascular morbidity, found in the subgroup of BAC-positive women in our study confirmed this relation. The negative association between BAC and smoking is unexpected but consistent with the finding of Kemmeren et al.4 The major limitation of our study is a potential bias of risk factor data obtained by questionnaire rather than direct and objective measurement. Our findings suggest that BAC may be a practical and inexpensive screening tool for the detection of cardiovascular risk in women. The existence of BAC on mammography may be a useful marker of women at higher risk for ASCVD or with unrecognized heart disease. 1. Feig SA, D’Orsi CJ, Hendrick RE, Jackson VP, Kopans DB, Monsees B. American College of Radiology guidelines for breast cancer screening. Am J Roentgenol 1998;171:29 –33. 2. Eaker ED, Chesebro JH, Sacks FM, Wenger NK, Whisnant JP, Winston M. Cardiovascular disease in women. Circulation 1993;88:1999 –2009. 3. 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;5:483– 487. 4. Kemmeren JM, van Noord PA, Beijerinck D, Fracheboud J, Banga J, van der Graaf Y. Arterial calcifications found on breast cancer screening mammograms and cardiovascular mortality in women. The DOM Project. Am J Epidemiol 1998;147:333–341. 5. Cowen AR, Launders JH, Jadav M, Brettle DS. Visibility of microcalcifications in computed and screen-film mammography. Phys Med Biol 1997;42:1533– 1548. 6. Shaw CC, Wang T, King JL, Breitenstein DS, Chang TS, Harris KM, Baratz AB, Ganott MA, Reginella R, Simkin JH, Gur D. Computed radiography versus screen-film mammography in detection of simulated microcalcifications: a receiver operating characteristic study based on phantom images. Acad Radiol 1998;5:173–180. 7. Leinster SJ, Whitehouse GH. Factors which influence the occurrence of vascular calcification in breast. Br J Radiol 1987;60:457– 458. 8. Kemmeren JM, Beijerinck D, van Noord PA, Banga J, Deurenberg JM, Pameijer FA, Graaf Y. Breast arterial calcifications. Association with diabetes mellitus and cardiovascular mortality. Radiology 1996;201:75–78. 9. Baum JK, Comstock CH, Joseph L. Intramammary arterial calcifications associated with diabetes. Radiology 1980;136:61– 62. 10. Shmitt EL, Norbeck JM, Threatt B. Incidence of mammary intraarterial calcification: an age-matched control study. South Med J 1985;78:1440 –1442.
BRIEF REPORTS
217