Abstract
BACKGROUND: Previous research assessed the relationship between individual complications of pregnancy and risk of cardiovascular disease (CVD). However, complications of pregnancy frequently coexist, and their synergistic effects may potentially amplify the maternal cardiovascular risk. This study aimed to assess the joint effect of multiple complications of pregnancy on future CVD in women. METHODS: We included 157,034 women aged 40-69 years with at least one live birth from the UK Biobank. Cox proportional hazards models were used to assess the joint association between six pregnancy complications (gestational diabetes mellitus, hypertensive disorders of pregnancy, stillbirth, miscarriage, low birth weight, and macrosomia) and subsequent cardiovascular outcomes. Subgroup analyses were performed to examine the effects of pregnancy complications on CVD across different subgroups. RESULTS: Compared to those without pregnancy complications, women with three or more complications had higher risks of total CVD (hazard ratio: 1.66; 95 % confidence interval: 1.40-1.96), coronary artery disease (1.79; 1.39-2.32), stroke (1.73; 1.12-2.70), atherosclerotic cardiovascular disease (ASCVD) (1.90; 1.54-2.34), and non-ASCVD (1.65; 1.34-2.04). A stronger association was noted in women aged 40-49 years for total CVD (2.35; 1.64-3.37) than other age groups. In addition, the associations between multiple complications of pregnancy and total CVD were partly mediated by hypertension, dyslipidemia, and diabetes in middle life (proportion of mediation: 7.8 %, 2.5 %, and 11.6 %). CONCLUSIONS: Women with a higher number of pregnancy complications demonstrated progressively increased risks of cardiovascular outcomes, which were partly mediated by hypertension, dyslipidemia, and diabetes in middle life. These findings underscore the importance of monitoring CVD in women with multiple complications of pregnancy.