BREAST ARTERIAL CALCIFICATIONS IN MAMMOGRAPHY AS CARDIOVASCULAR RISK FACTOR

NEW YORK, NY — Breast arterial calcification (BAC) on digital mammography is better than standard cardiovascular risk factors and as good as two commonly used risk calculators for identifying women with coronary artery calcification (CAC), a new study shows.^[1]

"Women's cardiac health has been relatively neglected both in research and in practice, and this is potentially a very accessible way with no extra money, no extra radiation to determine a women's risk factor for cardiovascular disease, so I think the time perhaps really is right for it," lead author and radiologist Dr Laurie Margolies (Icahn School of Medicine at Mount Sinai, New York City) told heartwire from Medscape.

There are other data showing a link between BAC and coronary artery disease and a few studies correlating BAC with CAC, but this is the first study to demonstrate the strong quantitative association of BAC with CAC, the authors report in an article published online March 24, 2016 in the JACC: Cardiovascular Imaging and scheduled for presentation at the upcoming American College of Cardiology 2016 Scientific Sessions.

Radiologists must distinguish BAC from calcification in breast tissue when reading a mammogram, but BAC findings are not currently reported.

Margolies is hoping increased attention to this issue will spur demand for BAC to be routinely included in mammography reports, just as reporting of breast density is now required in at least 20 US states.

During a press briefing highlighting the research, American College of Cardiology vice president Dr Mary Norine Walsh (St Vincent Heart Center, Indianapolis, IN) said screening for breast cancer and heart disease at the same time might be considered a "twofer" for women and that the study results could be "practice changing, life changing, and maybe guidelines changing for frequency of and who should be screened for mammography going forward."

Measuring Breast and Coronary Calcium

The study involved 325 asymptomatic women who had both a digital mammogram and a nongated chest computed tomography scan within 1 year of the other. A total of 33 women had established coronary artery disease, leaving 292 women (mean age, 61.5 years) for the primary analysis.

A score of 4 or higher denoted moderate CAC, which was calculated using the 12-point ordinal scoring system. CAC was noted in 47.6% of women.

BAC was also scored on a 12-point scale based on the number of breast vessels involved, the length of the vessel involved, and the density of calcium in the lumen. As with the CAC score, BAC results were divided into three categories of increasing severity: 0, 1 to 3, and 4 to 12.

BAC was present in 42.5% of women and was associated with increasing age (P<0 .0001="" hypertension="" i="">P

=0.0007), and chronic kidney disease (P<0 .0001="" p="">

Agreement between the BAC and CAC scores was also highly significant (P<0 .0001="" authors="" p="" report.="" the="">

No particular pattern has been observed for BAC, but "even if you had a tiny bit, that correlated with having calcification in the coronary arteries," Margolies said.

The overall accuracy of BAC higher than 0 for CAC higher than 0 was 70%, with sensitivity, specificity, and positive and negative predictive values of 63%, 76%, 70%, and 69%, respectively.

In unadjusted analyses, BAC from 4 to 12, age, hypertension, diabetes, and chronic kidney disease were significant for having CAC higher than 0, but after adjustment, only BAC from 4 to 12 (odds ratio [OR] 3.2), age (OR 2.0), and hypertension (OR 2.2) remained significant.

The authors then examined the relationship between BAC and CAC and the Framingham Risk Score (FRS) and 2013 Cholesterol Guidelines Pooled Cohort Equations (PCE).

For all patients, agreements for FRS risk categories with CAC and BAC risk categories were only 57% for CAC and 55% for BAC.

Agreement with PCE risk categories was even lower, at 47% for CAC and 54% for BAC.

"The relatively poor agreement of BAC and CAC risk categories with the FRS and PCE risk categories parallels the generally poor correlation of calcified plaque with risk-factor–based algorithms," the authors explain.

BAC was equivalent to both risk-factor–based paradigms for the identification of women with a CAC higher than 0, with an area under the curve of 0.73 compared with 0.72 for the FRS and 0.71 for PCE.

Notably, a further analysis that also included the 33 patients with established coronary artery disease revealed significant additive value of BAC to both FRS and PCE.

Why Is BAC Uptake Lagging?

Part of the reason BAC has not taken off is that coronary artery calcium itself has not fully penetrated cardiology, despite CAC testing being included in guidelines, study coauthor and cardiologist Dr Harvey Hecht (also with Mount Sinai) told heartwire .

"Given that it's a leap for cardiologists to understand the concept of [CAC] and act upon it, it's a further leap to go from [BAC] detected on a scan for which it was not the primary indication and incorporate that into medical practice," he added.

Other stumbling blocks are the lack of randomized trials showing BAC improves outcomes, something cardiologists are still looking to trials such as the ongoing ROBINSCA study to provide for coronary artery calcium, Hecht noted.

"Remaining a silent bystander waiting for another study and preserving the status quo should not be an option," Dr Khurram Nasir and Dr John McEvoy (Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD) write in an accompanying editorial.^[2]

They argue that the most implicating finding of the current study is BAC's robust positive predictive value of nearly 70% for identifying women with presence of CAC. Even among younger women, one in two with BAC had demonstrable CAC.

The finding of BAC in 42.5% of women is higher than estimates in the literature of 10% to 12%, the editorialists acknowledge, but suggest this may be attributable to the use of digital mammography and a risk-enriched cohort requiring chest computed tomography scans.

Still, they estimate that two to three million women would be identified with premature coronary atherosclerotic disease if BAC were found in even 10% of the roughly 37 million mammograms performed each year.

"You could initiate preventive strategies in nearly 2 to 3 million women each year without any other further intervention. This is low-hanging fruit," Nasir told heartwire . "It needs to be recognized, our medical communities need to be educated, and it needs to be incorporated into standards of care and traditional pathways."

The editorialists go one step further suggesting that in selected women, triple computed tomography screening for breast cancer, lung cancer, and atherosclerosis "seems like a viable and realistic option," although Nasir admits this may be years off.

"We need to streamline efforts among all our communities and break the silos [between] what's happening in radiology, oncology, cardiology, and primary prevention and come together to work on this very important issue," he added.

The study was funded by the Flight Attendants Medical Research Institute. Margolies has disclosed no relevant financial relationships; Hecht is a consultant for Philips Medical Systems. Disclosures for the coauthors are listed in the article. Nasir reports advising for Quest Diagnostics and consulting for Regeneron. McEvoy reports no relevant financial relationships.