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Objective:
Cardiovascular disease (CVD) remains the leading cause of death in the United States and reductions in female cardiovascular mortality have lagged behind men, highlighting the need for improved CVD risk assessment among women. Benign axillary lymph nodes (LNs) enlarged by radiolucent hilar fat deposition are an emerging marker of adiposity that can be incidentally detected on routine screening mammograms. However, it is not known if fat-enlarged LNs are associated with cardiovascular disease risk.

Materials and Methods:
We performed a retrospective review of all women aged 40–75 years without known coronary artery disease who had a routine screening mammogram, and cardiovascular risk factors available in the EMR within 1 year of the index mammogram from January 1, 2011 to December 31, 2012. We evaluated major adverse cardiovascular events (MACE) within 10 years of the index mammogram. We used clinical parameters at the time of the index mammogram to determine high estimated CVD risk via the pooled cohort equation (PCE), defined by the American Heart Association as > 7.5% likelihood of MACE within 10 years. Screening mammograms were evaluated by two breast imagers to measure the length of the largest visible axillary LN in each breast in the mediolateral oblique view. The largest visible node was chosen for analysis for each patient. The association between lymph node size, 10-year CVD risk, MACE, Type 2 diabetes (T2DM), hypertension (HTN), low density lipoprotein (LDL), age, and BMI was examined by logistic regression.

Results:
Among 1216 women included in our cohort, 907 (74.6%) had a visible axillary LN on the index mammogram, and 232 (19.1%) women had fat-enlarged nodes, defined as > 20 mm in length due to an expanded fatty hilum. Women with fat-enlarged nodes had a high risk of CVD defined by PCE (OR = 2.6, 95% CI 1.5–4.2), as well as a higher prevalence of T2DM (OR = 4, 95% CI 2.1–7.7) and HTN (OR = 2.5, 95% CI 1.6–4.0). Fat-enlarged nodes were also associated with a trend toward higher risk of MACE (OR = 1.7, 95% CI 0.9–3.1) and LDL (OR = 1.4, 95% CI 0.9–2.1).

Conclusion:
Fat-enlarged axillary nodes on screening mammograms are a predictor of high CVD risk, T2DM, and HTN. Fat-enlarged axillary nodes may represent an opportunistic imaging biomarker of T2DM and CVD risk in women who undergo screening mammography, a widely utilized screening examination among 76.4% of eligible women in the U.S. If validated in larger studies, incorporating fat-enlarged nodes into CVD risk models has the potential to improve CVD risk stratification without additional cost or additional testing. Fat-enlarged axillary lymph nodes visualized on screening mammography may increase the ability to identify women who would benefit from CVD risk reduction strategies and more intensive risk assessment with coronary artery CT. These results support further investigation of fat-enlarged lymph nodes, particularly with studies leveraging AI evaluation of mammographic fat-enlarged LNs and cardiometabolic disease.