UC San Diego

Objective: Reproductive events have been linked with increased cardiovascular risk in women, but whether they are associated with pre-clinical peripheral arterial disease (PAD) has been understudied. We evaluated associations between reproductive factors and later-life ankle-brachial index (ABI), femoral artery intima-media thickness (fIMT), and femoral plaques. Methods: Cross-sectional analysis of 707 multiethnic women who participated in a follow-up exam of the San Diego Population Study in 2007-2011. To assess associations between reproductive factors (age at menarche, parity, age at menopause, surgical menopause, hormone therapy) with ABI, and Doppler ultrasound measurements of common and superficial fIMT, linear regression was used; for femoral plaque presence, logistic regression was used. Models were adjusted for age, race/ethnicity, and cardiometabolic factors. We tested interactions of reproductive factors with menopause type (natural vs. surgical). Results: Women were on average 71 years old, and 56% were non-Hispanic White. Reproductive factors were not associated with fIMT, femoral plaque presence, or ABI. There were significant interactions between menopause type (surgical vs. natural) and oral contraceptive use (-β: 0.04, p = 0.03) for ABI, as well as between menopause type and parity (β: 0.11, p = 0.05) and age at menopause (β: 0.001, p = 0.05) for fIMT. Among women with natural menopause, oral contraceptive use was associated with higher ABI (β: 0.03, p = 0.007) and older age at natural menopause was related to greater fIMT (β: 0.009, p = 0.06). Among women with surgical menopause, nulliparity was marginally associated with greater fIMT (β: 0.33, p = 0.07). Conclusions: Reproductive history may not be independently associated with later-life lower extremity atherosclerosis in women. Studies are necessary to confirm findings and examine pregnancy-related exposures in relation to pre-clinical PAD.