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Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
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2016 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, article id e009880Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population.

DESIGN: Cohort study.

SETTING: Sweden.

POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion.

METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking.

MAIN OUTCOME MEASURES: Dementia, CVD, stroke.

RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81).

CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.

Place, publisher, year, edition, pages
2016. Vol. 6, no 1, article id e009880
National Category
General Practice Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-278956DOI: 10.1136/bmjopen-2015-009880ISI: 000369993900137PubMedID: 26801467OAI: oai:DiVA.org:uu-278956DiVA, id: diva2:907254
Funder
EU, European Research Council, 259679Swedish Research Council, 2014-3561Available from: 2016-02-26 Created: 2016-02-26 Last updated: 2018-02-22Bibliographically approved
In thesis
1. Preeclampsia and the Brain: Epidemiological and Magnetic Resonance Studies
Open this publication in new window or tab >>Preeclampsia and the Brain: Epidemiological and Magnetic Resonance Studies
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.

This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).

In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.

In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.

In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.

In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.

Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1432
Keywords
preeclampsia, eclampsia, seizure, MRI, MRS, IVIM, dementia, cardiovascular disease, magnesium, cerebral organic osmolytes, perfusion
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-341999 (URN)978-91-513-0245-4 (ISBN)
Public defence
2018-04-13, Gustavianum, auditorium minus, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 2014-3561
Available from: 2018-03-22 Created: 2018-02-22 Last updated: 2018-04-24Bibliographically approved

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Nelander, MariaÅkerud, HelenaWikström, JohanWikström, Anna-Karin

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