Aims

The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women.

Methods and results

We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing. Among 4908 women, 354 incident cases of AF (7%) were ascertained after a mean (standard deviation) of 7 (2) years of follow-up. In Cox regression adjusting for a propensity score for BAC, BAC presence vs. absence was not significantly associated with AF [hazard ratio (HR) = 1.12; 95% confidence interval (CI), 0.89-1.42; P = 0.34]. However, a significant (a priori hypothesized) age by BAC interaction was found (P = 0.02) such that BAC presence was not associated with incident AF in women aged 60-69 years (HR = 0.83; 95% CI, 0.63-1.15; P = 0.26) but was significantly associated with incident AF in women aged 70-79 years (HR = 1.75; 95% CI, 1.21-2.53; P = 0.003). No evidence of dose-response relationship between BAC gradation and AF was noted in the entire cohort or in age groups separately.

Conclusion

Our results demonstrate, for the first time, an independent association between BAC and AF in women over age 70 years.

Background

Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD.

Methods

A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD.

Results

Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status.

Conclusions

Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

Background

Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown.

Methods

Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD.

Results

After 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4-10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48-5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37-3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83-12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22-11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33-8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66-8.59; p < 0.0001). No significant association was found between hsTnI and BAC. Adding hsTnI to a model containing the Pooled Cohorts Equation resulted in significant and clinical important improved calibration, discrimination (Δ C_index = 6.5; p = 0.02) and reclassification (bias-corrected clinical NRI = 0.18; 95% CI, -0.13-0.49 after adding hsTnI categories).

Conclusions

Our results support the consideration of hsTnI as a risk enhancing factor for CVD in asymptomatic women that could drive preventive or therapeutic decisions.