Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study

Abstract

IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTSThis 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.EXPOSURES Presence or absence of preeclampsia among women with 1 or more pregnancies. MAIN OUTCOMES AND MEASURES Incident stroke in later life.RESULTS 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 cholesterollowering 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). CONCLUSIONS AND RELEVANCEThe 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.

Information needs and experiences from pregnancies complicated by hypertensive disorders: a qualitative analysis of narrative responses

“…This is a critical time in the natural history of HDP as blood pressure is often higher and eclampsia is more likely to occur postpartum [ 25 , 26 ] reinforcing the need for targeted communication and postpartum monitoring. Responders also requested information regarding their long-term health, specifically cardiovascular disease, for which women with preeclampsia are at risk of [ 27 – 32 ]. Several also indicated poor counseling regarding the recurrence of HDP [ 33 , 34 ] and some were incorrectly informed that HDP would not recur.…”

“…Indeed, HDPs represent a unique pregnancy complication as they can present heterogeneously, progress rapidly, and have immediate high acuity impact on both mother and fetus, requiring complex medical decision-making. HDPs also have long-term impact on maternal and offspring health [ 30 – 32 , 35 ], adding complexity to communications. As most pregnancies proceed without incident, diagnosing HDP can be challenging, especially in nulliparas.…”

Impact of preeclampsia/eclampsia on hemorrhagic and ischemic stroke risk: A 17 years follow-up nationwide cohort study

“…Reviewing the literature, previous studies reported the stroke risk for 3 months antepartum, and 3 days, 6 weeks, 6 months, and 12 months postpartum [ 14 ]. For follow up time exceeded one year after delivery, only one longitudinal cohort study recently had ever reported the later-life stroke incidence [ 24 ], but their study did not compare stroke risk in different time intervals. Because no specific time division criteria could be referred, we conventionally divided the follow-up time into 0–5, 5–10, and 10–15 years, and further divided the 0–5 years close to delivery into 0–1, 1–3, and 3–5 years.…”

Is there a role of proinflammatory cytokines on degenerin‐mediated cerebrovascular function in preeclampsia?

“…Cerebrovascular disorders are the leading cause of maternal mortality in PE, predominantly as a consequence of intracerebral hemorrhage or stroke (Bushnell et al, 2014; Duley, 2009; Fishel Bartal & Sibai, 2020; Miller, 2019). According to a recent cohort study based on the data of Framingham Heart Study, women with PE have a more than threefold higher risk for future stroke (de Havenon et al, 2021). Cerebrovascular disorders of PE include increased blood‐brain barrier (BBB) permeability, subsequent brain edema, visual disturbances, seizures (eclampsia), neurovascular dysfunction, perivascular microhemorrhage, microinfarcts, arteriolar vasculopathy, and stroke (Hammer & Cipolla, 2015; Kontos et al, 1978; Kontos et al, 1981; Logue et al, 2016; Mahendra et al, 2021; Miller, 2019; Paulson, 2002; Ryan et al, 2011; Warrington et al, 2014; Younes & Ryan, 2019; Zunker et al, 2000).…”