| Summary: | <h4>Background</h4>There is increasing evidence that breast arterial calcification (BAC), an incidental finding on 3-29% of mammograms, could be used to screen for coronary artery disease (CAD). We conducted a systematic review to assess the associations between BAC and CAD and its risk factors (hypertension, hypercholesterolemia, diabetes mellitus and smoking).<h4>Methods and findings</h4>MEDLINE and EMBASE databases and references of relevant papers were searched up to 18 February 2020 for English language studies that evaluated the associations of BAC and CAD and its risk factors. A single reviewer extracted all data and assessed study quality with verification by another independent reviewer, if required. Across 31 studies (n = 35,583; 3 longitudinal and 28 cross-sectional studies) that examined the association of BAC and CAD, the OR was 2.61 (95% CI 2.12-3.21; I2 = 71%). Sub-analysis of studies that graded BAC severity using the 4- (4 studies) or 12-point scale systems (3 studies) revealed an association with CAD and moderate-severe BAC (OR 4.83 (95%CI 1.50-15.54) and OR 2.95 (95%CI 1.49-5.84), respectively) but not mild BAC (OR 2.04 (95%CI 0.82-5.05) and OR 1.08 (95%CI 0.42-2.75), respectively). BAC was associated with hypertension (42 studies; n = 32,646; OR 1.80; 95% CI 1.47-2.21; I2 = 85%) and diabetes mellitus (51 studies; n = 53,464; OR 2.17; 95% CI 1.82-2.59; I2 = 75%) but not with hypercholesterolemia (OR 1.31; 95%CI 0.97-1.77; I2 = 67%). Smoking was inversely associated with BAC (35 studies; n = 40,002; OR 0.54; 95% CI 0.42-0.70; I2 = 83%). Studies mostly included symptomatic women. Marked heterogeneity existed and publication bias may be present.<h4>Conclusions</h4>BAC is associated with CAD, diabetes mellitus and hypertension and inversely associated with smoking. Whether BAC could screen for CAD cannot be determined from current published data due to the lack of larger prospective studies. A consensus approach to quantifying BAC may also facilitate further translation into clinical care. PROSPERO: CRD42020141644.
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