Abstract
Preeclampsia and cardiovascular disease (CVD) might share heritable underlying mechanisms. We investigated whether preeclampsia in daughters is associated with CVD in parents. In a register-based cohort study, we used Cox regression to compare rates of CVD (ischemic heart disease, ischemic stroke, myocardial infarction) in parents with ≥ 1 daughters who had preeclampsia and parents whose daughters did not have preeclampsia in Denmark, 1978-2018. Our cohort included 1,299,310 parents, of whom 87,251 had ≥ 1 daughters with preeclampsia and 272,936 developed CVD during 20,252,351 years of follow-up (incidence rate 135/10,000 person-years). Parents with one daughter who had preeclampsia were 1.19 times as likely as parents of daughters without preeclampsia to develop CVD at age < 55 years (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.25). Having ≥ 2 daughters who had preeclampsia yielded an HR of 1.88 (95% CI 1.39-2.53). The corresponding HRs for CVD at ≥ 55 years of age were 1.13 (95% CI 1.12-1.15) and 1.27 (95% CI 1.16-1.38). Patterns of association were similar for all CVD subtypes. Effect magnitudes did not differ for mothers and fathers (p = 0.52). Analyses by timing of preeclampsia onset in daughters suggested a tendency toward stronger associations with earlier preeclampsia onset, particularly in parents < 55 years. Preeclampsia in daughters was associated with increased risks of CVD in parents. Increasing strength of association with increasing number of affected daughters, equally strong associations for mothers and fathers, and stronger associations for CVD occurring before age 55 years suggest that preeclampsia and CVD share common heritable mechanisms.