Introduction:
Breast arterial calcifications (BAC) are a type of medial arterial calcification observed at mammography. They are more prevalent among diabetes patients and thought to be associated with increased cardiovascular risk, but high quality longitudinal studies are scarce. We aimed to investigate the association of BAC with risk of different types of cardiovascular outcomes.
Methods:
We performed a series of case-cohort studies nested within the PROSPECT-EPIC cohort, including a random subcohort (n = 1672), and incident cases of coronary heart disease (n=1050), stroke (n=399) peripheral artery disease (n=257), cardiovascular mortality (n=250), and type 2 diabetes (n=526). At baseline BAC was scored as absent, mild, moderate or severe by experienced radiologists. The average follow-up time was 12.0(±1.9) years. We calculated hazard ratios(HRs) using Cox proportional hazards models, adapted to the case-cohort design through Prentice-weighting and adjusting for traditional cardiovascular risk factors.
Results:
Of the women in the sub cohort with mammograms available (n=1540), 133 women (8.6%) had BAC in at least one breast. Grade was scored as mild in 75 women (4.9%), moderate in 39 women (2.5%) and severe in 19 women (1.2%). BAC presence was borderline significantly (0.05<p<0.10) associated with risk of coronary heart disease, stroke and cardiovascular mortality, with adjusted HR estimates ranging from 1.42 to 1.58. Much larger effect sizes were found for women with the most severe grade of BAC, as they had a HR of 3.43 (95% CI 1.85-6.37) for coronary heart disease, a HR of 3.19 (95% CI 1.52-6.72) for stroke, a HR of 2.92 (95%CI 1.02-8.35) for peripheral artery disease and a HR of 3.55 (95%CI 1.48-8.52) for cardiovascular mortality compared to women without BAC.
Conclusions:
BAC presence is modestly associated with cardiovascular disease, with an approximately 3-fold increased risk for the severest grade of BAC, independent of traditional risk factors. This indicates a possible contribution of a medial, non-atherosclerotic pathway to cardiovascular disease events. Whether BAC is a marker of medial arterial calcification in different vascular beds needs to be further investigated.