Clinical Imaging 49 (2018) 48–53

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Clinical Imaging
journal homepage: www.elsevier.com/locate/clinimag

Breast Arterial Calcification on screening mammography can predict MARK

significant Coronary Artery Disease in women
⁎
Brendan S. Kellya,c, , Emer ScanlONb, Helen Heneghanc, Ciaran E. Redmonda, Gerard M. Healya,
Enda Mc Dermottc, Eric J. Heffernana, Ruth Prichardc, Sorcha Mc Nallya,d
a
Department of Radiology, St Vincent's University Hospital, Elm Park Dublin 4, Ireland
b
School of Medicine and Medical Science, UCD, Belfield D4, Ireland
c
Department of Breast, Endocrine and General Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
d
Breast Check, St Vincent's Healthcare Group, Elm Park Dublin 4, Ireland

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Breast Arterial Calcification (BAC) on digital mammography has been associated with an increased
Breast Arterial Calcification risk of Coronary Artery Disease (CAD). We aimed to investigate the association of BAC with findings on Coronary
Computed Tomography Coronary Angiography Computed Tomography Angiography (CCTA) within a cohort of women from the national breast screening
Breast cancer screening program.
Outcomes research
Methods: Symptomatic women (chest pain) aged between 50 and 65 who underwent a CCTA and who also had a
Coronary Artery Disease
screening mammography between 2014 and 2015 were recorded. BAC and CAD-RADS™: Coronary Artery
Disease–Reporting and Data System were scored by separate blinded specialist radiologists. Cardiac risk factors
were recorded. Patients' cardiac follow up (with Exercise Stress Test, Percutaneous Coronary Intervention or
echocardiography) and cardio-protective medications were also documented.
Results: 219 eligible women underwent a CCTA. Of these, 104 patients also underwent digital mammography.
Using standard linear regression BAC was identified as a significant predictor of CAD-RADs ≥3 disease. Using
binomial logistic regression, BAC remained associated with CAD-RADs ≥3 (p = 0.023). A significantly higher
proportion of patients with BAC > 1 were on cardio-protective medications (p = 0.041) and had medications
initiated or changed, or had further cardiac investigation (p = 0.037 and p = 0.019, respectively) than those
with no BAC, after a mean follow-up of 20.6 (range 15–27) months.
Conclusion: BAC diagnosed on 2 yearly screening mammography predicts CAD-RADs ≥3 disease in sympto-
matic patients.

1. Introduction cancer-specific mortality is well established [6] and is currently re-

Coronary Artery Disease (CAD) remains a leading cause of death in
women [1]. While several risk factors have been identified [2], for
many patients the first presentation of Coronary Artery Disease is a
cardiac event [3]. The incidence of CAD is declining in men, this is not
the case in women [4]. A calcium score derived from Computed To-
mography Coronary Angiography (CCTA) predicts risk over and above
the Framingham Risk factors [5] but carries a radiation burden and
issues of timely access. The calcium score is calculated from non-con-
trast studies, rather than being a luminal assessment like CCTA.
The efficacy of screening mammography in decreasing breast-
commended by the European Society of Breast Imaging [7].
BreastCheck is the state-body tasked with its implementation in the
Republic of Ireland. The potential benefits of breast cancer screening
are clear, with all women aged 50–65 years (at the time of data col-
lection) being offered biennial mammograms.
Since the 1990s, an association between Breast Arterial Calcification
(BAC) identified on screening mammography and CAD has been pro-
posed [8]. Recent studies have added further weight to the argument
that BAC predicts calcium scoring on CCTA [9,10]. It appears to do so
over and above traditional Framingham risk factors [10]. BAC is age-
dependent [10], and whether these risk factors are pertinent to women

Abbreviations: BAC, Breast Arterial Calcification; CAD, Coronary Artery Disease; CAD-RADS, Coronary Artery Disease – Reporting and Data System: An Expert Consensus Document of
the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed
by the American College of Cardiology; CCTA, Coronary Computed Tomography Angiogram; EST, Exercise Stress Test; PCI, Percutaneous Coronary Intervention
⁎
Corresponding author at: Department of Radiology, St Vincent's University Hospital, Elm Park Dublin 4, Ireland.
E-mail address: brendanskelly@me.com (B.S. Kelly).

https://doi.org/10.1016/j.clinimag.2017.10.021
Received 23 August 2017; Received in revised form 15 October 2017; Accepted 30 October 2017
0899-7071/ © 2017 Elsevier Inc. All rights reserved.
B.S. Kelly et al.
of screening age remains to be identified. Therefore, any extra potential
benefit gleaned from the investigation will be at no extra radiation
exposure to the patient or cost to the state. If mammography can be
shown to predict CT findings it has the potential to give information
about risk of developing CAD without extra radiation exposure.
No evidence exists linking BAC to the recently published CAD-RADs
[11] scoring system. CAD-RADs > 3 prompts functional assessment and
may be of interest to cardiologists or primary care physicians when
assessing cardiovascular risk. There are little data outlining outcomes
for those patients with BAC and whether this increased risk translates
into changes in clinical decision making or further investigation re-
mains unknown.
Our study aimed to identify if there was an association between BAC
on breast screening mammography and CAD-RADs score in sympto-
matic women. We also followed up our patients for a minimum of
15 months (range 15–27 mean 20.6) to determine if there was any
change in their cardiac management compared to those who do not
have BAC.
2. Method
2.1. Study population
Ethical approval for this retrospective cohort study was obtained
from our Institutional Review Board. The institution's Picture Archive
and Communication System (PACS) was searched for female patients
who were underwent CCTA in 2014 and 2015, yielding 484 patients.
The indication for CCTA in every case was “chest pain” i.e. all patients
included were symptomatic of cardiac disease. Of these, 219 women
were within the BreastCheck screening age and 110 had a digital
screening mammogram examination within the study period. Six pa-
tients were excluded due to incomplete data and a total of 104 women
were included for analysis (Fig. 1). Demographic, cardiac risk factors,
current cardiac medications and alterations were collected and ana-
lyzed. Cardio-protective medications included low dose aspirin or other
anti-platelet, lipid lowering therapies, anti-arrhythmic and anti-
hypertensive agents.
2.2. Reporting protocol
Fig. 2A and B outline the BAC and CCTA scoring systems used.
Mammograms were scored by a specialist breast radiologist for the
presence or absence of BAC, and then graded 1–4 according to Mostavi
et al. [12]. Digital mammography was performed using either Hologic
Selenia Dimensions or Siemens Mammomat Inspiration mammography
systems. CCTA were all performed using Siemens Somatom single
source 64 Slice CT, with retrospective ECG gating, mAs 800–850, kVp
120, gantry rotation 330 milliseconds, with a slice overlap of
Fig. 1. Flow chart showing inclusion of patients in our sample.
49
Clinical Imaging 49 (2018) 48–53
0.3–0.5 mm and collimation 0.6–0.75 mm. All studies were reported by
one of 2 specialist cardiac radiologists and scored according to the CAD-
RADs reporting system. Both the breast and cardiac radiology specia-
lists were blinded to all other information about the patients.
2.3. Statistical analysis
Data were analyzed using IBM SPSS software version 23.0 (IBM
Corp, New York, United States). Continuous variables are described as
mean (standard deviation) or median (range) values, and compared by
Student t-test or Mann-Whitney U test, depending on distribution of the
data. Categorical variables are reported as percentages and compared
by x2 test. Linear regression was used to determine which variables
were associated with a CAD-RADs score of 3 or greater. Binomial lo-
gistic regression was then used to identify clinical or radiological fac-
tors associated with CAD-RADs controlling for confounding variables.
To determine if the grade of BAC was associated with CAD-RADs,
Pearson's correlation coefficient was measured. To identify a potential
difference between the groups' cardiac management a One-Way
Analysis of Variance (ANOVA) was used. All analyses were 2-tailed with
the threshold of significance < 0.05.
3. Results
3.1. Study cohort
Table 1 outlines the demographics and cardiac risk factors for the
total study population, and for the subgroups differentiated by the
presence or absence of BAC. Table 2 demonstrates these data according
to patients' CAD-RADs score (CAD-RADs > 3 vs. CAD-RADs < 3). The
grading of BAC and CAD in this population is illustrated in Table 3.
The prevalence of BAC was 14%, and CADRADs > 3 disease was
identified in 8%. Mean age was 58.93 (50–65) years. In terms of ab-
solute numbers, among the BAC-positive population, there was a higher
prevalence of hypertension, dyslipidaemia, diabetes mellitus, smoking
status, known cardiovascular disease and family history of cardiovas-
cular disease. However, there was no statistically significant difference
in the prevalence of these risk factors between those patients with or
without BAC. ANOVA to find any potential difference between the two
groups overall was also not significant (p = 0.14).
3.2. Associations
Linear regression analysis identified BAC as the only variable sig-
nificantly associated with CAD-RADs. Within this our sample the effect
of traditional risk factors was not seen, possibly due to Type II error as a
trend to significance was seen. Binary logistic regression was performed
to control for potentially confounding CAD risk factors and this de-
monstrated that BAC remained associated with CAD-RADs 3 or greater.
There was also a strong positive correlation between BAC and CAD-
RADs score, Pearson's correlation coefficient 0.354, p < 0.001.
3.3. Clinical outcomes
At a mean of 20.6 months following CCTA 44% of patients were
taking some cardio-protective medication. A significantly higher pro-
portion of these (p = 0.041) had a BAC score > 1. By the end of follow
up, 36.5% of patients had a change in their medications or had a car-
diac medication initiated in the time from the CCTA. This proportion
was also significantly higher in the patients with BAC than those
without (57 Vs 33.3% p = 0.037). Finally, a significantly greater pro-
portion of the BAC + group had further functional imaging within the
follow-up period compared to the BAC-group (71% vs. 36.67% re-
spectively, p = 0.019) (Table 4).
B.S. Kelly et al. Clinical Imaging 49 (2018) 48–53

Fig. 2. A. CAD-RADs scoring system.

B. BAC scoring system: A. Grade 1: No vascular calcifications. B. Grade 2: Few punctate vascular calcifications, no tram track or ring calcifications. C. Grade 3: Coarse or tram track
calcifications affecting < 3 vessels. D. Grade 4: Coarse or tram track calcifications affecting ≥ 3 vessels.

4. Discussion mammography are commenced on medications and proceed to func-

This study demonstrates that in a sample of 104 women who pre-
sented with chest pain and had a subsequent CCTA, BAC identified on
screening mammography predicts a CAD-RADs score of 3 or greater
(Fig. 3). This held true controlling for age and for the Framingham risk
factors. A CAD-RADs score of ≥ 3 prompts consideration of functional
assessment and anti-ischaemic and preventative medications. Further-
more, we have shown that patients with BAC seen on screening
tional imaging more often than those without.
Several studies have proposed a link between BAC and cardiac risk.
In a systematic review of the literature, Hendriks et al. demonstrated an
increased risk of CAD in those women with BAC with an Odds ratio of
1.32–1.44 [13] and large cohort studies have shown that cardiovascular
mortality increases in the presence of BAC [14]. Two meta-analyses of
this data confirm a positive association between BAC and the presence
of cardiac disease [15,16]. Recent data have shown that BAC is

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B.S. Kelly et al. Clinical Imaging 49 (2018) 48–53

Fig. 2. (continued)

Table 1 Table 2
Demographics by BAC status. Demographics by CAD-RADs 0 or > 0.

All BAC + (%) BAC − (%) p value All CAD + (%) CAD − (%) p value

N 104 14 90 N 104 37 67
Age 58.93 59.4 58.87 0.83 Age 58.93 59.1 57.8 0.78
HTN 70 10 (71) 60 (67) 0.71 HTN 70 25 (68) 45 (67) 0.96
Hyperlipid 41 8 (57) 33 (37) 0.148 Hyperlipid 41 16 (43) 25 (37) 0.556
DM 26 5 (36) 20 (22) 0.319 DM 26 6 (16) 20 (30) 0.09
Smoking 17 4 (29) 13 (14) 0.263 Smoking 17 5 (14) 12 (18) 0.54
CVD 36 5 (36) 31 (34) 0.926 CVD 36 12 (32) 24 (36) 0.726

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B.S. Kelly et al. Clinical Imaging 49 (2018) 48–53

Table 3
Prevalence of BAC and CAD-RADs scores in our sample.

No % p value

BAC 1 90 87 0.78
2 8 8 0.96
3 6 6 0.556
4 0 0 0.09
CAD 0 67 64 0.54
1 24 23 0.726
2 4 4
3 7 7
4 A/B 1 1

Table 4
Summary of follow-up (outcomes) data.

All BAC+ BAC- p value

n 104 14 90
Cardiac med 46 (44) 10 (71) 36 (40) 0.041
Change in med w/i 1 year 38 (36.5) 8 (57) 30 (33.3) 0.037
Functional imaging 43 (41) 10 (71) 33 (36.67) 0.019

significantly associated with coronary artery calcification scores on

CCTA in varied populations; first in a cohort of American women [17]
and more recently in heterogeneous American populations [9,10]. De-
spite Zgheib et al. refuting the significance of BAC on mammography
[18], the weight of evidence is in favor of an association between BAC
and CAD. A range of grading systems for Breast Arterial Calcification
has been proposed. Most papers refer either to the presence or absence
[9] of BAC or to a 1–4 grading system [12] or alternative system enu-
merating calcified arteries [10]. Regarding CCTA, a calcium score de-
rived from this imaging modality has been increasingly used as a sur-
rogate marker for CAD. The Agaston Score of coronary artery
calcification is also used as an indicator of CAD [9]. Others use non-
gated CCTA scans and derive a calcium score from these [10]. Due to
the potential for inter-reader variability in the reporting of stenosis on
CCTA the American College of Radiology proposed the CAD-RADs
scoring system in 2016 to standardize reporting of CCTA. This scoring
system stratifies patients based on the vessel with maximum stenosis or
other clinically relevant stenosis.
The data clearly show that in this cohort of patients BAC is asso-
ciated with CAD-RADs. We demonstrated this in two ways. The simplest
is through Pearson Correlation which shows that as the BAC score in-
creased from 1 to 4 the CAD-RADs score also increased. The correlation
coefficient of 0.354, while moderate, was highly significant and sug-
gests that the data for our sample are likely to representative of the
population. Secondly using simple linear regression the only variable
that appeared to significantly contribute to the model predicting CAD- Fig. 3. A. A high grade BAC 3 lesion and its associated CCTA (panel B) demonstrating
RADs > 3 disease controlling for age and other cardiac risk factors was plaque in the left anterior descending artery from one patient in our sample.
BAC. Furthermore this held true for the binary logistic regression that
again showed association of BAC and CAD-RADs. Previous research out that these mechanisms of calcification have modifiable risk factors
outlined above has shown a strong association between age and BAC. in common with breast cancer- the initial reason for the mammogram.
This was not evident in our cohort most likely due to our cohort coming This indicates the potential for the screening mammogram to be a
from the screening population aged 50–65. platform to reduce the risk for both breast cancer and cardiovascular
The mechanism through which BAC may be associated with CAD is disease by identifying common risk factors for separate pathogenic
complex and incompletely understood. It is likely that the pathogenesis processes.
of BAC and CAD are separate as BAC is medial arterial calcification A common criticism [20] for the associations of BAC and CAD is the
compared to the intimal calcification that causes coronary disease [19]. variability in definitions for both conditions. This study utilizes two
While both are associated with increased morbidity and mortality, in- objective scoring systems to quantify BAC and CAD. This should
timal calcification is associated more with atheromatous disease and hopefully add to the reproducibility of the current study. The grade 1–4
medial more with diabetic calcification. Both processes are different system proposed by [12] has been used in previous research. We chose
from the malignant type of calcification seen in breast cancer [19]. to use this scoring system as it presents an objective method of grada-
While this may mean that potential treatment for conditions associated tion of BAC. There have been calls for a gradation of BAC that would
with different types of calcification differ they share common risk fac- not compromise workflow [20] such as a mild, moderate severe scoring
tors. Indeed in an editorial in Circulation in 2017 [20] it was pointed system. This is similar to that employed in the current study (with the

52
B.S. Kelly et al.
inclusion of an “absent” grade).
This study for the first time, in relation to BAC, uses CAD-RADs, a
scoring system in the mold of BI-RADs which has standardized the re-
porting of breast pathology to great effect and has been successfully
replicated with LI-RADs and TI-RADs (and others) for liver and thyroid
pathology. We believe that the correlation of the two scoring systems
adds weight to their veracity as descriptors of BAC and CAD on CCTA
respectively.
BAC predicted CAD-RADs 3 or greater in our sample. This is sig-
nificant because a CAD-RADs of ≥3 prompts consideration of func-
tional assessment and anti-ischaemic and preventative medications.
Had the patients' cardiologists or primary care physicians been aware of
the presence of BAC then they could potentially have had initiated risk
reducing therapy or functional imaging before presentation with a
cardiac event. Many low risk women who do not reach the criteria for
risk modifying therapy have cardiac events as their index presentation
[3]. Knowledge of the BAC score in light of this and other recent evi-
dence could well be taken into consideration either by the general
practitioner seeing a patient routinely or indeed by the cardiologist
faced with a symptomatic patient in the emergency department. While
our cohort is comprised of symptomatic patients, further research is
needed to demonstrate whether our data are generalizable to the wider
screening population beyond those with chest pain. A 2013 review [21]
suggested that the presence of BAC on mammography be taken into
account when assessing cardiac risk but did not advocate the reverse
and we feel our data support this.
This study has several limitations, including a relatively small
sample size and the retrospective nature of the study. Despite increasing
utilization of CCTA it is still an uncommonly performed test and used
predominantly in symptomatic patients. Given that our study cohort
were all symptomatic, it is not yet possible to generalize the study
findings to the wider breast screening population. Certainly before any
recommendation of clinical intervention based on BAC in an asymp-
tomatic patient could be made a larger prospective trial is needed.
There is a likely selection bias in this study population given that in-
cluded patients were symptomatic of CAD and opted into the breast
cancer screening program. CAD-RADs score is merely a surrogate for
CAD, and before BAC can be used in clinical practice as a novel cardiac
risk factor then relevant clinical outcomes must also be proven to have
an association with BAC. This study is the first to demonstrate an as-
sociation between clinical outcomes and BAC, but without a national
database we cannot be certain that patients did not present to other
hospitals. We echo previous calls for a bias-free outcomes trial to fur-
ther elucidate the strength of BAC as a cardiac risk factor [10].
5. Conclusion
Within our relatively small study cohort of symptomatic patients
BAC on screening mammography was associated with a CAD-RADs
score of ≥ 3 and demonstrated a positive correlation with CAD-RADs
score. Furthermore, at a mean of 20.6 months' follow-up a significantly
higher proportion of patients with BAC were on cardiac medications or
had those medications increased. They were also more likely to have
undergone functional cardiac imaging. These data add weight to the
argument of a positive independent relationship of BAC to CAD and
suggest the screening mammogram is a potential source of information
about women's cardiac risk.
53
Clinical Imaging 49 (2018) 48–53
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