Abstract
Contemporary research suggests an association between preeclampsia and later-life stroke among women. To our knowledge, no research to date has accounted for the time-varying nature of shared risk factors for preeclampsia and later-life stroke incidence. To assess the relative risk of incident stroke in later life among women with and without a history of preeclampsia after accounting for time-varying covariates. This population-based cohort study was a secondary analysis of data from the Framingham Heart Study, which was conducted from 1948 to 2016. Women were included in the analysis if they were stroke free at enrollment and had a minimum of 3 study visits and 1 pregnancy before menopause, hysterectomy, or age 45 years. Data on vascular risk factors, history of preeclampsia, and stroke incidence were collected biannually. Participants were followed up until incident stroke or censorship from the study. Marginal structural models were used to evaluate the relative risk of incident stroke among participants with and without a history of preeclampsia after accounting for time-varying covariates. Data were analyzed from May 2019 to December 2020. Presence or absence of preeclampsia among women with 1 or more pregnancies. Incident stroke in later life. A total of 1435 women (mean [SD] age, 44.4 [7.7] years at the beginning of the study; 100% White) with 41 422 person-years of follow-up were included in the analytic sample. Of those, 169 women had a history of preeclampsia, and 231 women experienced strokes during follow-up. At baseline, women with preeclampsia were more likely to be younger, to be receiving cholesterol-lowering medications, to have lower cholesterol and higher diastolic blood pressure, and to currently smoke. The association between preeclampsia and stroke in the marginal structural model was only evident when adjustment was made for all vascular risk factors over the life course, which indicated that women with a history of preeclampsia had a higher risk of stroke in later life compared with women without a history of preeclampsia (relative risk, 3.79; 95% CI, 1.24-11.60). The findings of this cohort study suggest that preeclampsia may be a risk factor for later-life stroke among women after adjustment for time-varying vascular and demographic factors. Future research is warranted to fully explore the mediation of this association by midlife vascular risk factors.
Highlights
Hypertensive disorders of pregnancy are a major cause of morbidity and mortality in the peripartum period and predispose women to an elevated risk of cardiovascular, cerebrovascular, and renal disease later in life.[1]
The association between preeclampsia and stroke in the marginal structural model was only evident when adjustment was made for all vascular risk factors over the life course, which indicated that women with a history of preeclampsia had a higher risk of stroke in later life compared with women without a history of preeclampsia
The findings of this cohort study suggest that preeclampsia may be a risk factor for later-life stroke among women after adjustment for time-varying vascular and demographic factors
Summary
Hypertensive disorders of pregnancy are a major cause of morbidity and mortality in the peripartum period and predispose women to an elevated risk of cardiovascular, cerebrovascular, and renal disease later in life.[1]. Preeclampsia can result in acute cerebrovascular complications, including stroke and intracranial vasculopathy,[2] and has been associated with an increase in the risk of stroke in later life. Existing research has not fully accounted for time-varying midlife risk factors that could bias the association between preeclampsia and later-life stroke.[2,3,4,5] To address this limitation, we used data from the Framingham Heart Study (FHS), which enrolled 2873 women who had up to 32 follow-up visits every other year. Data were collected on cardiovascular risk factors and stroke incidence.[6] We hypothesized that preeclampsia was associated with later-life stroke after adjustment for time-dependent covariates at every study visit
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