Reproductive factors and the risk of incident peripheral arterial disease hospitalisation or death: A cohort study of UK Biobank participants.

Abstract

Objectives: Associations between reproductive factors and risk of peripheral arterial disease (PAD) are not well established. This study examined reproductive factors and hormone use in relation to incident PAD risk in women.

Study design: UK Biobank cohort study, excluding participants with prior diagnosis of PAD. Self-reported reproductive factors included were age at menarche, parity-related factors (including live birth, miscarriages, stillbirths, abortions), menopause-related factors (including reproductive years, age at menopause, hysterectomy and oophorectomy) and exogenous hormone use (including OCP and HRT use). Participant baseline data were linked with hospital admission data and the national death register to identify first record of PAD. Poisson regression estimated sex-specific incidence rates (IRs) of PAD per 10,000 person years and Cox proportional hazard regressions estimated confounder-adjusted hazard ratios (adjHRs) linking reproductive factors with incident PAD. The association between number of children and PAD was also examined for men and compared between the sexes.

Results: Over a median follow-up of 13·2 years 2,942/272,557 women and 5,432/227,403 men developed PAD. Early and late menarche (age <12 and >14 years) was associated with increased PAD risk (adj HR 1·43 95% CI[1·32, 1·55], p<·001, 1·36 [1·23, 1·49], p<·001, respectively). Reduction in PAD risk was observed for an older age at first birth (adjHR 0·95 [0·94, 0·96], p<·001, per year). While, cumulative increased PAD risk was observed per miscarriage (adjHR 1·06 [1·01, 1·11] p=·027), per stillbirth (adjHR 1·18 [1·03, 1·36] p=·014) and per abortion (adjHR 1·09 [1·01, 1·18], p=·028). A longer duration of reproductive years, later natural menopause, and use of oral contraceptives (adjHR 0·85 [0·78, 0·93], p<·001) were associated with reduced PAD risk. Hysterectomy or oophorectomy were associated with increased PAD risk (adjHR 1·24 [1·13, 1·35], p<·001, 1·24 [1·10, 1·39], p<·001, respectively). Associations between the number of children and PAD were U-shaped and similar for both sexes, with a multiple-adjusted HR of 1·13 ([1·00, 1·25], p=·041) for women and 1·25 ([1·16, 1·34], p<·001) for men, with 4 or more children.

Conclusions: Reproductive factors are associated with increased risk of PAD and should be considered in future risk stratification.