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For other articles and previous issues click here. June 28, 2004 Is There
a Future for Cardio-Mammography? Several studies have found a connection between mammography-detected breast calcifications and coronary artery disease. Are there any clear answers? New research suggests that the presence of breast arterial calcifications on mammograms may be an indicator of an increased risk for cardiovascular disease. In a Mayo Clinic study of 1,880 women who had previously undergone coronary angiograms, reviews of the women’s mammograms showed that those with arterial calcifications in one or more major arteries of the breast were 60% more likely to have coronary artery disease than those without breast calcifications. When the researchers corrected for age, those with major arterial breast calcifications had a 20% increased risk of cardiovascular disease compared with those without calcifications. The jury is still out on how accurate mammograms alone are for predicting heart disease risk. But Mayo Clinic researchers say breast arterial calcifications could be one factor that indicates increased heart disease risk. “Smoking, high blood pressure, hypertension, high cholesterol, and diabetes are all more important risk factors than breast arterial calcifications,” says Kirk Doerger, MD, a Mayo Clinic radiology resident and author of the study. “But, the presence of breast arterial calcifications in young women who have not been screened for heart disease and have no other risk factors may be an indicator that their cardiovascular risk should be checked.” Previous studies have shown that women with breast arterial calcifications have a 40% increased risk of dying from heart disease. Although the Mayo Clinic study supports these earlier findings, questions remain about just how useful mammograms alone could be in predicting heart disease risk—especially in the general population. “The clinical implications of breast arterial calcifications are still not clear,” Doerger says. “But there’s no harm in taking note of them—especially in asymptomatic women.” An important bias of the Mayo Clinic study was that participants may have already been at higher-than-average risk for heart disease since they were undergoing coronary angiograms. “The results from the population in our study may not be applicable to the general population of women undergoing mammograms,” says Doerger. In their analysis of the study results, the authors also found that breast calcification is most likely a risk factor for coronary artery disease but may not correlate to the amount of disease. “The amount of risk and who’s at risk must be clarified,” says study coauthor Dana Whaley, MD, senior associate consultant in radiology at the Mayo Clinic, Rochester, Minn. “It appears that the amount of calcification in the breasts is not as important as whether or not calcification is present.” To further elucidate the role of breast arterial calcifications in predicting heart disease risk, the researchers are designing a study in which randomly selected women will be assessed for coronary artery disease risk factors via mammograms over an extended time period. The women’s mammograms will be assessed every year for 10 years, and the women will be prospectively followed. “If we can identify patients who are at increased risk due to breast arterial calcifications and show that they have more heart attacks, then five, 10, or 15 years down the road, we may be able to advise them to start exercising and treat risk factors such as high cholesterol aggressively,” Whaley says. Whaley also cautions that women who have breast arterial calcifications are not at immediate risk for coronary artery disease. “It’s a long-term risk,” he says. “The major value of our study is that we can say that breast arterial calcification is one more piece of the puzzle that we have to consider in deciding whether or not patients might be at increased risk for heart disease.” Peter Berger, MD, a cardiologist and professor of medicine at the Mayo Clinic and a study coauthor, agrees that breast arterial calcification may one day have a role in helping to assess heart disease risk. “Vascular calcifications are, without question, a sign of atherosclerosis,” he says. “With the current recommendations, in which women over the age of 45 undergo mammography every year, we have a wonderful and inexpensive tool to detect unsuspected atherosclerosis without additional testing.” However, Berger acknowledges that questions remain about whether or not atherosclerosis in the breast is associated with atherosclerosis in the peripheral and cerebral vascular beds. “I suspect it is,” he says. “That’s why women who have breast arterial calcifications might need to undergo further evaluation.” “Certainly, there’s something going on [with breast arterial calcification] that needs to be studied in depth,” Whaley adds. “It may be a complex relationship. Is breast arterial calcification a marker for an unknown risk factor or is it its own risk factor?” One of the first major studies on breast arterial calcification and heart disease began 20 years ago in the Netherlands and found a 40% increased risk of mortality from coronary artery disease in women with breast arterial calcifications. The group of scientists that conducted this research published a paper on the relationship between breast arterial calcifications, diabetes mellitus, and cardiovascular and noncardiovascular mortality in the October 1996 issue of Radiology. In this study of 12,239 women aged 50 to 68, the researchers found that breast arterial calcifications were present in 9% of all women and in more than 15% of diabetic women. In all women, breast arterial calcifications were associated with a 40% increased risk of dying from heart disease. In diabetic women, the presence of breast arterial calcification was associated with a 90% increase in cardiovascular mortality. All the women were screened with xeromammograms during two visits between 1975 and 1978. Breast arterial calcification was regarded as being present if the characteristic pattern of two parallel calcific lines (the artery wall imaged longitudinally) or a calcific ring configuration (the artery wall imaged en face) was present on the mammogram of the right, left, or both breasts. The researchers then followed the women through a mortality register established through general practitioners in the city of Utrecht. The results indicated that breast arterial calcifications and the mortality rate showed a strong increase with advancing age, especially in diabetic women. The researchers found an increased cardiovascular mortality of 40% for all women with breast arterial calcification after adjustment for age, smoking, parity, and obesity. In their discussion, the researchers noted that intimal arterial calcification, a hallmark of atherosclerotic disease, has been strongly associated with increased mortality from cardiovascular disease. Yet, medial arterial calcification (the type present in breast arterial calcification) has been regarded as a normal feature of aging with little or no clinical importance. The researchers concluded that their study revealed that breast arterial calcification could be an additional independent risk factor for coronary artery disease in women older than 50, especially in women with diabetes. As well as having a 90% increased risk of cardiovascular mortality, women with diabetes and breast arterial calcifications had an 80% increased risk of noncardiovascular mortality when compared with women with diabetes but without breast arterial calcification. Whaley notes that this earlier study relied on initial single-view mammograms performed from 1975 to 1977. Modern mammograms are obtained with film screen or digital techniques using two views per breast, which may alter the amount of calcification detected. The population undergoing screening has also changed dramatically in terms of lifestyle risk for heart disease. Thus, the significance of breast arterial calcifications seen on mammograms may now be somewhat different, he says. A more recent study also found that breast arterial calcifications seen on today’s more sophisticated mammograms may be an indicator of increased cardiovascular risk. Pavel Crystal, MD, and a team of Israeli researchers conducted the study, which was published in the American Journal of Cardiology in July 2000. In the study, researchers asked 865 randomly selected women referred for mammography to complete a questionnaire assessing major risk factors for atherosclerosis—including age, hypertension, smoking, diabetes, family history of heart disease, dyslipidemia, and menopause. Data on women with histories of myocardial infarction, angina pectoris, abnormal coronary angiography, coronary bypass surgery, and stroke were also collected. The researchers noted that modern mammography’s increased resolution has improved the visibility of microcalcifications. Today, microcalcifications as small as 100 micrometers in diameter can be visualized. The objective of this study was to estimate the value of breast arterial calcifications pictured on today’s state-of-the-art equipment, the researchers said. Two experienced mammographers, blinded to the questionnaire results, analyzed the women’s mammograms independently for the presence of breast arterial calcifications. They defined breast arterial calcification as the presence of linear calcium deposit along the periphery of tapered structures whose configuration was typical of arteries, distinct from breast ducts. The mammograms were designated as positive for breast arterial calcification if calcifications were found on one of the two standard views in the right or left breast or in both breasts. When the researchers analyzed the data, they discovered that women whose mammograms were positive for breast arterial calcifications were older (a mean age of 65 vs. 54) than those whose mammograms were negative. The presence of four out of six analyzed major risk factors was notably greater in women whose mammograms were positive for breast arterial calcifications. Breast arterial calcifications were also associated with a nearly twofold increase in the existence of atherosclerotic cardiovascular disease or greater than two major risk factors for heart disease. The researchers noted that the prevalence of breast arterial calcifications (17% of the women had positive mammograms) in their study was significantly higher than previously reported. “This fact may be partly explained by the enhanced sensitivity of modern mammography. Also, in our study population, there is a greater prevalence of risk factors such as diabetes that can affect prevalence of breast arterial calcifications,” they wrote. However, the presence of breast arterial calcifications—along with most of the major risk factors for heart disease—was “striking,” the researchers said. They concluded that mammograms may be a practical and inexpensive screening tool for the detection of cardiovascular risk in women. “The existence of breast arterial calcification on mammography may be a useful marker of women at higher risk for atherosclerotic cardiovascular disease or with unrecognized heart disease,” they wrote. In interviews, however, Crystal noted that mammography is not a reliable means of screening patients who are already known to have heart disease. In these cases, exams such as electrocardiogram, exercise stress test, and CT are clearly superior in monitoring heart disease and damage. When Crystal’s study was presented at the European Congress of Radiology in Vienna, Austria, in 2001, scientists voiced concerns similar to those of the Mayo Clinic researchers. How much breast artery calcium should be considered normal or abnormal? Or, is any breast arterial calcification a sign of increased heart disease risk? The questions remain unanswered. If mammograms are to serve as useful tools for detecting heart disease risk, standards will have to be set and followed by each radiologist who reads mammogram films to determine which women should be referred for further testing. In the end, answers to questions about the possible use of mammography as a screening tool for heart disease need to be found in further research, Mayo Clinic scientists say. “We need much more information about the significance of breast arterial calcification,” Whaley says. Thus, the researchers hope to start their large prospective study as soon as possible and will tie it to an already ongoing coronary angiography study. “This issue is too important to wait a long time for answers,” Whaley says. “We need to know how useful the association between breast and arterial calcification and increased cardiovascular risk truly is.” — Barbara Boughton is an award-winning medical writer living in the San Francisco area. She has contributed to The Lancet, Oncology, and the book Dr. Koop’s Self-Care Advisor. |
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