American Journal of Preventive Cardiology · Nov 18, 2025

Endothelial dysfunction and cardiovascular outcomes in pre-menopausal women with high vs low breast fat accumulation: The role of TSP-1

By Sardu C, Nicoletti GF, Trotta MC et al.

BACKGROUND: In premenopausal women, adipose tissue accumulation of the breast gland is an independent risk factor for cardiovascular diseases (CVDs) and major-adverse-cardiac-events (MACE). AIMS: We aimed to evaluate endothelial dysfunction (ED) via brachial artery flow-mediated dilation (FMD), and to assess serum endothelin-1 (ET-1), thrombospondin-1 (TSP-1), and MACE at 5-year follow-up among women with different degrees of breast fat accumulation (BFA). METHODS: Women aged 40-55 years undergoing mammography were consecutively enrolled and classified into high-BFA and low-BFA groups; those with baseline ED were excluded. ED, inflammatory markers, ET-1, TSP-1, and MACE were reassessed at 5-year follow-up. RESULTS: At follow-up, ED occurred in 44 % of high-BFA vs. 28.3 % of low-BFA women, and MACE in 11.2 % vs. 2.5 % (p < 0.05). ED was independently predicted by pre-diabetes (HR 1.14, 95 % CI 1.03-1.68) and TSP-1 (HR 1.08, 95 % CI 1.01-1.12). Predictors of MACE included impaired FMD (HR 1.19, 95 % CI 1.06-1.46), reduced LVEF (HR 1.03, 95 % CI 1.01-1.06), elevated WBC (HR 1.61, 95 % CI 1.40-1.83), ET-1 (HR 1.46, 95 % CI 1.21-1.77), TSP-1 (HR 1.17, 95 % CI 1.01-1.32), and high BFA (HR 1.968, 95 % CI 1.96-2.01). CONCLUSIONS: Women with High-BFA vs Low-BFA showed higher rates of ED and MACE, along with increased inflammatory/oxidative markers and elevated ET-1 and TSP-1 levels. TSP-1 independently predicted both ED (HR 1.081) and MACE (HR 1.170). ET-1 levels predicted greater risk of MACE (HR 1.459). High BFA (HR 1.65) and impaired FMD (HR 1.189) independently predicted MACE at 5 years.

doi.org/10.1016/j.ajpc.2025.101349Open accessPubMed 41378318Populations