Breast arterial calcifications as a biomarker of cardiovascular risk: radiologists’ awareness, reporting, and action. A survey among the EUSOBI members

Cardiovascular disease still represents the leading cause of death for women [1]. Disparities in mortality rates still subsist by sex among age groups, with less favourable trends in young women [2, 3]. Recommended risk stratification algorithms—including traditional risk factors, sex, race, and ethnicity—do not adequately perform in women, leading to potential risk underestimation and subsequent undertreatment [4, 5]. Likely, traditional cardiovascular risk factors actually confer different risks for women and men. On the other hand, unique non-traditional risk factors such as pregnancy complications, oral contraception, hormonal fertility, menopausal therapies, and systemic autoimmune disorders play a crucial role in the complex biological pathway towards cardiovascular disease in women [6]. Moreover, the estrogenic dysregulation occurring in menopause—but also in premature ovarian insufficiency and obesity—favours breast arterial calcifications (BAC) development [7‐10].

BAC on mammography are known to be strongly associated with cardiovascular disease, independently from other known cardiovascular risk factors [11], and their inclusion in cardiovascular risk algorithms has been advocated to improve cardiovascular outcomes in women [12, 13]. The current strength of this association, however, is not sufficient to warrant a clinical application in preventive cardiology. Indeed, the lack of validated and reproducible quantification methods allowing for risk stratification still represents an open issue. Nevertheless, no universal recommendations do exist on whether and how to report BAC and how to deal with them, discuss with women, or refer to cardiologists [5, 7].

In this context, the European Society of Breast Imaging (EUSOBI) launched a survey among its members to investigate the radiologist attitude about BAC awareness, reporting, communication, and actions. The results of this survey are reported in this paper.

The response rate to this survey, reaching more than a third of all EUSOBI members, shows a relatively high interest of breast radiologists towards BAC. Over 80% of participants were aware of the association between BAC and cardiovascular risk and over 60% declared to include BAC in mammography reports when they are present. Such data show how even in an era of highly specialised medicine and radiological subspecialties, about 30% of EUSOBI members display a comprehensive approach towards disease prevention, beginning to consider mammography as a tool that could combine breast cancer prevention with cardiovascular prevention in women.

There is robust evidence linking BAC with well-known cardiovascular risk factors, such as increasing age, parity, diabetes mellitus, and hyperlipidaemia, all associated with a higher BAC prevalence [5, 7, 11] than that (12.7%) currently reported among the general female population attending breast cancer screening programmes [11]. Several studies suggested that BAC presence is associated with a risk of coronary heart disease up to three times higher than in the general population [8, 14‐16], independently from other known cardiovascular risk factors and from the presence of coronary artery disease [14, 15].

Notably, BAC and coronary atherosclerotic plaques are the expression of two different pathophysiological processes. While BAC are the consequence of Mönckeberg medial calcific sclerosis—a non-occlusive disease resulting in thicker and stiffer vessels—coronary plaques involve the vascular intima, leading to luminal narrowing and vessel occlusion [17].

This survey also revealed that, among radiologists reading in a population-based screening mammography programme, the majority is aware of BAC cardiovascular meaning and includes BAC in mammogram reports (when BAC are present), even if report forms, per se, do not provide such input. This is a positive proactive behaviour. First of all, this improves primary care physicians’ perception of BAC meaning and potential. Secondly, it facilitates the creation of large datasets, encouraging prospective studies with known cardiovascular outcomes to ascertain if BAC may improve cardiovascular risk stratification over traditional approaches. Finally, from the patient’s perspective, receiving such information is desirable. A recent study centred on a self-administered survey involving 419 women undergoing screening or diagnostic mammography highlighted how women have an overwhelming preference to be informed if BAC are found in their mammograms [18]. Of note, while cardiovascular risk awareness among women remains low despite the high toll paid in terms of cardiovascular mortality [19, 20], findings by Margolies et al [18] strongly hint that, if properly informed, women would become actively involved in tailored preventive strategies focused on cardiovascular disease, beginning to consider it not only as a “male problem”.

Oral communication with women about their BAC status is pursued by 45.5% of respondents which routinely include BAC in mammography reports, even though in 47.2% of cases doing it only when BAC burden or progression is deemed severe. If so, 44.2% proceed to investigate cardiovascular anamnesis and 39.5% refer women to a cardiologist. Interestingly, all these action habits were more frequently undertaken in Eastern European countries and by radiologists working in private hospitals and private practice. Such findings may be partially explained considering that these three geographic areas (Western Europe, Eastern Europe, and non-European countries) do not mirror official indications, rather reflect a similarity of routine practices both in screening and diagnostic setting.

Italy, along with the UK, had the greater number of respondents to this survey (53/378, 14.0% Italian and 38/378, 10.1% English respondents), as for the greater number of members within EUSOBI (187/1084, 17.2% Italian and 80/1084, 7.4% English members). This result could also be influenced by the lesser diffusion of organised screening programmes in some countries, as well as by differences in the number of examinations and allotted time performed in private setting, factors which unfortunately do not emerge from our survey. Finally, different socio-cultural contexts or medico-legal issues may also come into play.

Most of the respondents, 64.8%, qualitatively describe BAC as “present”, while just over a fourth assess them through an ordinal visual scale, the latter undoubtedly representing a considerable step from a mere subjective and qualitative evaluation towards a semi-quantitative assessment. Only one radiologist (0.4%) declared to manually perform a quantitative assessment, while computer-aided tools were absolutely missing.

Binary BAC classifications hinder the comprehensive stratification of women into multiple cardiovascular risk levels and the identifications of women who would mostly benefit from a tailored disease prevention [7]. The target population for a cost-effective further risk assessment is primarily represented by individuals at intermediate cardiovascular risk; indeed, in a low-risk population, the rationale for preventive intervention is missing, while in a high-risk population, further risk assessment would not reasonably impact on a formerly recommended pharmacological treatment [21]. Nevertheless, the major source of bias for qualitative or semi-quantitative methods for BAC evaluation has been—up to now—their poor reproducibility [7, 22]. Albeit easily detectable on mammography, BAC topological complexity and vessel overlap on two-dimensional mammographic projections make both the identification and quantification of BAC quite difficult to standardise, preventing robust validation and subsequent clinical application [5, 7]. A sound and reproducible BAC quantification, ideally through a continuous scale, is paramount for cardiovascular risk stratification. Valuable information on this issue will probably come from the MINERVA study, the first large prospective study using a continuous mass (in milligrams) score for BAC assessment. These results will hopefully contribute to determine whether this validated method [23] is indeed capable of predicting coronary heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, and total cardiovascular disease on a large population. Answers to these questions will also clarify if adding BAC burden classification to prediction models based on traditional risk factors effectively stimulates a reclassification of cardiovascular disease risk in women [24].

An automated tool could also represent a useful solution for BAC quantification and is what we must strive for. Recently, the use of artificial intelligence systems for BAC segmentation was investigated. In particular, a deep convolutional neural network was trained to discriminate between BAC and non-BAC pixels from digital mammography images, obtaining good performances both in BAC detection and calcium mass quantification [25]. However, such systems, although promising, are still far from being validated and subsequently applied, large-scale studies being needed to obtain further improvements.

Limitations of this survey include, first, a potential selection bias among radiologist members of the EUSOBI, who of course supposedly display special interest in breast imaging and in keeping updated with correlated research on such topic. Therefore, awareness about BAC meaning and reporting attitude are potentially overestimated and not generalisable to the whole radiological community. Secondly, the response rate was below 50%, as indeed typically observed in similar surveys [26], with our 35.2% response rate being higher than expected and representing an excellent data. Finally, more detailed questions about education, habits, and technical challenges were avoided to reach a good compliance in terms of response rate.

In conclusion, this survey illustrated that, among EUSOBI members, more than 80% of respondents are aware of BAC implications in terms of cardiovascular risk, and that more than 60% include BAC on mammogram reports when they are present. However, BAC quantitative estimates are not performed, with very few exceptions.

Large-scale studies are now needed to ascertain the role of BAC assessment in the comprehensive framework of female cardiovascular disease prevention, provided that BAC quantitative methods are available. Furthermore, efforts should be pursued in discussing with women their BAC status and its meaning. Reporting BAC may prove a step towards promoting cardiovascular disease prevention in women via mammography. This would ultimately confer the ability to concomitantly influence the course of two leading causes of death in women, i.e. breast cancer and cardiovascular disease, to a widely diffused and endorsed population-based screening programme.