Abstract

Introduction: Reductions in cardiovascular mortality among women lag behind men. There is a critical need for improved primary prevention of major adverse cardiovascular events (MACE) in women. We examined if breast artery calcification (BAC), detected on screening mammograms, prognosticates long-term MACE. Methods: In this retrospective study of consecutive women age 40-75 years without coronary disease from 2011-12, followed for 10 years at Dartmouth-Hitchcock Medical Center, we recorded baseline mammograms, clinical parameters and 10-year MACE risk was estimated via the pooled cohort equation (PCE). The association of BAC and MACE was examined by a multivariable, interactive logistic regression model with MACE as dependent variable, adjusting for confounders and an interaction of BAC with 3 strata of PCE predicted risk: low (<5%), moderate (5-7.5%) and high (>7.5%). The primary endpoint was MACE over 10 years. Results: Among 1216 women, 19% had BAC. Women with BAC were older, had more hypertension and diabetes, and a higher baseline PCE score. Over 10 years of follow-up, 21% of women with BAC developed MACE compared to 11% women without BAC (p<0.001). This association was independent of risk factors and statin use. Among women with low (< 5%) risk of MACE, those with BAC had an 18% incidence of MACE, compared to 7% in women without BAC (OR 2.8, 95% CI 1.5 - 5.0) (Fig 1A). The incremental increase in MACE in patients with BAC decreased with higher PCE-predicted risk. Peak interaction occurred at a PCE-predicted risk of 10% (Fig 1B). Among women with a PCE-predicted risk <10%, BAC was a strong predictor of MACE with an attributable fraction of 20% (Fig 1B). Conclusions: BAC is a strong, independent predictor of MACE, particularly in women at low risk by PCE. Although PCE is used widely to risk stratify women for MACE, our study suggests it severely underestimates risk in women with a low PCE score. Further prospective trials are needed to validate these findings.

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