Breast Arterial Calcification as a Cardiovascular Risk Factor

Despite significant progress, cardiovascular disease remains the leading cause of death among women.¹ For many women, the first indication of a problem comes only when they are diagnosed with a heart attack or a stroke. But what if these same women had been notified years earlier about their elevated risk for cardiovascular disease (CVD), based on data from routine health screenings? Could some of these life-altering events have been prevented?

Breast arterial calcification (BAC), often seen as an “incidental” finding on standard screening mammograms, has an increasing body of work to support its use as an imaging biomarker of CVD risk.² Given that a large percentage of women over 40 years of age undergo annual mammograms, BAC is widely accessible without the need for additional testing or radiation. However, its implementation in clinical practice remains virtually nonexistent.

Why are we allowing this risk marker to remain overlooked? While significant work remains to fully realize the potential of BAC, we urge the medical community to prioritize and implement systematic reporting of this important marker. Even in the absence of a perfect, evidence-based pathway for reporting and addressing BAC, we believe there are still compelling reasons to begin reporting it and considering it as a cardiovascular risk factor. Despite the challenges and the work that needs to be done, incorporating BAC into clinical practice today can already enhance the evaluation and management of cardiovascular risk in women.

BAC is associated with CVD outcomes and mortality even among women not considered to be at high risk, such as younger women and those without diabetes, hypertension, hyperlipidemia, chronic kidney disease, or known CVD.³ In fact, some studies have found that BAC is most predictive of outcomes in younger women (40-59 years of age), although it remains a predictor at older ages as well. This is one of the key reasons that BAC is an attractive candidate for identifying CVD risk in women who may not yet be aware they are at risk.

Among patients in higher risk categories, BAC can further refine risk assessment. For example, in women with diabetes, the presence of BAC was associated with a 2.5 times increased risk of cardiovascular events or all-cause death.³

The contribution of BAC to current cardiovascular risk stratification is an area of ongoing study. However, multivariable analyses have shown that BAC remains an independent predictor of outcomes, even when accounting for traditional CVD risk factors. Further research is needed to determine the extent to which BAC contributes to risk reclassification.

An interesting feature of BAC is that it seems to be especially predictive of heart failure, perhaps even more so than of atherosclerotic CVD.3, 4, 5 When BAC is associated with heart failure, some studies have shown that it is more strongly associated with nonischemic than ischemic heart failure. BAC, which accumulates in the media of blood vessels, may be more reflective of vascular stiffness and endothelial dysfunction, compared with coronary artery calcification, which resides in the intima of vessels and is more associated with atherosclerotic processes. The pathophysiology of BAC may reflect a stiff vasculature, which could explain its link to heart failure, but may also suggest an association with coronary microvascular dysfunction in women. The relation with heart failure also provides a framework for developing preventive algorithms in women with BAC, since we now have many examples of effective tools to intervene early and reduce development of heart failure in various at-risk populations.6, 7, 8, 9

There are significant advantages to using BAC for CVD risk stratification. It is widely available in women over 40 years of age, many of whom already undergo annual screening mammography for breast cancer detection, so it requires no additional cost or radiation exposure. Additionally, since most women have serial mammograms, BAC could be monitored over time—although the impact of longitudinal assessments on risk stratification is as yet unclear.

Another key benefit of BAC is that it may appear earlier than other traditional cardiovascular risk factors, making it a potentially valuable early biomarker of CVD risk. While BAC prevalence increases with age, it can already be found in up to 10% of women by the age of 40. Early identification of CVD risk could lead to early lifestyle and pharmacologic interventions for primary prevention. Furthermore, since BAC is predictive of outcomes in both low-risk and high-risk women, it could help those at risk for CVD who might otherwise be missed by current risk stratification methods.

Importantly, women are interested in knowing about their BAC status. A recent survey of women undergoing mammography found that 96% would want to know if they had BAC, including 100% of the women without known CVD.¹⁰

Approximately 30% of women who get a mammogram are aged 40 to 60 years. Of these, approximately 10% will have BAC, and at least half of those will also have additional, yet potentially unidentified, cardiovascular risk factors.² Starting today, when a woman is found to have BAC, it can serve as a valuable signal to take a closer look at her. This could include taking a detailed family and medical history (including asking about cardiometabolic disorders of pregnancy), performing blood work, checking blood pressure, and discussing lifestyle factors such as diet, exercise, and smoking. It can also include asking about symptoms and educating about the signs and symptoms of heart disease. This does not, and should not, automatically trigger advanced imaging such as a computed tomography coronary calcium score or the immediate initiation of statin therapy. However, it absolutely should prompt a comprehensive cardiovascular risk assessment—just as we would for any other patient identified with a significant cardiovascular risk factor.

Even if BAC's sole role today is to prompt clinicians to address and manage well-known risk factors such as inactivity, hypertension, and hyperlipidemia, its impact would be tremendously beneficial. Currently, only about 40% of adults with hypertension know they have it, and only one-fifth of those with hypertension have it under control.¹¹ Many women who do not regularly see a primary care provider still undergo annual mammograms. Reporting BAC on mammogram results could serve as an impetus to trigger an evaluation for known risk factors. This simple step could help identify at-risk women earlier and improve management of their cardiovascular risk factors. It might also encourage women to reconnect with or establish care with a primary care provider—where a comprehensive approach to risk factor modifications can begin. This would be a huge gain for cardiovascular health—and one that we can begin to reap today.

There is still much we do not know about BAC, and as we gather more data, the questions continue to multiply. Does the progression of BAC offer prognostic value beyond baseline measurements? How does the rate of BAC progression vary among women, and can this variability offer deeper insights into future cardiovascular risk? Do other risk markers modify the association of BAC with CVD outcomes? How do lifestyle and pharmacologic interventions influence the relationship between BAC and cardiovascular outcomes? Moreover, how do lifestyle changes and pharmacologic interventions impact BAC progression and associated outcomes? Finally, can we identify a specific subgroup of women with BAC who would benefit most from early interventions?

Currently, radiologists rarely report BAC, if at all. A recent survey by the Society of Breast Imaging found that while 85% of breast imaging radiologists were aware of the association between BAC and CVD, only 15% routinely included BAC data on their mammogram reports.¹² Assessing BAC adds time and complexity to a radiologist's workflow. Automated BAC assessment tools have been developed and may be crucial for seamless integration into workflows, though it could introduce additional costs.

So far, there is no consensus on how to report BAC. Similar to coronary artery calcification, both qualitative and quantitative methods can be used to assess and report BAC. The degree of BAC provides more information than its mere presence—though even simply identifying its presence is a valuable indication of risk.³ Ultimately, the radiology, cardiovascular, and primary care communities must collaborate to establish a practical workflow where reporting leads to meaningful action. These guidelines would pave the way for implementation and outcome studies, leading to the development of evidence-based treatment pathways. With time and further research, we can better understand the nuances of BAC interpretation, including how to tailor responses for younger vs older women, as well as in other patient subsets. Clear guidance is needed to help women and their clinicians interpret BAC findings and respond in ways that are both effective and cost-effective. Additional research is critical to support the development of these guidelines. Achieving this will take time, purposeful investigation, and coordinated efforts to build and implement care pathways. Without intentional efforts, care pathways will remain undeveloped.

Given that cardiovascular disease is the leading cause of death in women, we cannot afford to overlook any tool that could help identify risk and improve outcomes. While we work toward developing pathways and comprehensive guidelines for tomorrow, we must start using what we already know about BAC to inform care and reduce risk today. This is a call to action for clinicians and investigators to prioritize reporting and capturing BAC, ensuring that we use every available resource to combat this pervasive threat to women's health. Our patients deserve nothing less than our full commitment to leverage every opportunity to save lives.

Funding support and author disclosures

Dr Daniels has served as a consultant for CureMetrix. Dr Itchhaporia has reported that she has no relationships relevant to the contents of this paper to disclose.