Accepted Manuscript Systematic Review and Meta-analysis on Non-classic Cardiovascular Biomarkers after Hypertensive Pregnancy Disorders Sanne Visser, Wietske Hermes, MD Johannes C.F. Ket, René. H.J. Otten, Maria G. Van Pampus, M., PhD. Kitty W.M. Bloemenkamp, M.,PhD. Arie Franx, MD,PhD. Ben W. Mol, MD.,PhD. Christianne J.M.DE. Groot, MD,PhD PII:

S0002-9378(14)00242-7

DOI:

10.1016/j.ajog.2014.03.032

Reference:

YMOB 9732

To appear in:

American Journal of Obstetrics and Gynecology

Received Date: 11 November 2013 Revised Date:

9 February 2014

Accepted Date: 12 March 2014

Please cite this article as: Visser S, Hermes W, Ket JCF, Otten RHJ, Van Pampus MG, Bloemenkamp KWM, Franx A, Mol BW, Groot CJMD, Systematic Review and Meta-analysis on Non-classic Cardiovascular Biomarkers after Hypertensive Pregnancy Disorders, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.03.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

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Systematic Review and Meta-analysis on Non-classic Cardiovascular Biomarkers

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after Hypertensive Pregnancy Disorders

3 Sanne VISSER1,2, Wietske HERMES, MD1,3, Johannes C.F. KET4, René. H.J. OTTEN4, Maria G.

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VAN PAMPUS, M., PhD.2, Kitty W.M. BLOEMENKAMP, M.,PhD.6,

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Arie FRANX, MD,PhD.5, Ben W. MOL, MD.,PhD.7, Christianne J.M. DE GROOT, MD,PhD1.

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1. Obstetrics and Gynecology, VU University Medical Center, Amsterdam

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2. Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis, Amsterdam

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3. Obstetrics and Gynecology, Medical Center Haaglanden, the Hague

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4. Medical Library, VU University, Amsterdam

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5. Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht

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6. Obstetrics and Gynecology, Leiden University Medical Center, Leiden

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7. Obstetrics and Gynecology, Amsterdam Medical Center, Amsterdam

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Supported by a grant from Nuts Ohra Foundation, the Netherlands

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Corresponding author: Sanne Visser, MD, Onze Lieve Vrouwe Gasthuis, Department of

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Obstetrics and Gynecology, Oosterpark 9, 1091 AC Oost en Watergraafsmeer, Amsterdam,

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The Netherlands; phone: +31 020 5999111, e-mail: [email protected]

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Word Count: 250 (abstract) / 3794 (main text)

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Disclosure Statement: The authors report no conflict of interest.

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CONDENSATION

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Women with a history of hypertensive pregnancy disorders have significant elevated

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homocysteine levels and increased levels of biomarkers in areas of inflammation, thrombosis

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and angiogenesis.

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37 Short Title: Cardiovascular Risk after Pregnancy

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ABSTRACT

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Objective: The aim of this study is to investigate which non-classic cardiovascular biomarkers

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are associated with persistent endothelial dysfunction after pregnancy in women with a

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history of hypertensive pregnancy disorders compared to women with uncomplicated

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pregnancies.

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Study design: Systematic review and meta-analysis of observational studies.

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A search was performed in PubMed, Embase, Cochrane and Cinahl including articles from

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inception to 27 February 2013. Included were cohort studies and case-control studies. Cases

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were women with a history of hypertension in pregnancy, control subjects were women with

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a history of uncomplicated pregnancies.

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Of the 3136 found, 21 studies on 16 non-classic cardiovascular biomarkers are described in

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this review; 12 studies on 5 biomarkers were included in the meta-analysis.

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Results: Women with a history of hypertensive pregnancy disorders had a higher

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homocysteine level compared to women with a history of uncomplicated pregnancies (5

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studies; pooled mean difference 0.77ng/ml; 95% confidence interval 0.27 to 1.26; p 1 (20months)

Homocysteine (means)

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Mean: 7.8

Homocysteine (means) IL-6, PAI-1, TNF-α (medians)

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1 (15months)

Fibrinogen, VWF, tPA ICAM, VCAM, E-selectin (means) PAI-1(medians)

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0.5 (>6months)

Fibrinogen, IL-6, ICAM, VWF (means)

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Range:5-6

IL-6, VWF (medians)

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Mean: 6

PAI-1 (means) Ddimer, Fibrinogen, tPA (medians)

PT+T

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Mean: 6

VCAM, ICAM (means)

Not reported

Not reported

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Median: 4

Homocysteine (means)

Not reported

Not reported

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0.5 (6months)

TNFα (medians)

PT+T

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Median:9.4 (cases) 9.7 (controls)

sFlt , VEGF, E-selectin(medians)

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Cases 22.8 Controls 40.2

*Studies included in meta-analyses

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Systematic review and metaanalysis on nonclassic cardiovascular biomarkers after hypertensive pregnancy disorders.

The aim of this study was to investigate which nonclassic cardiovascular biomarkers are associated with persistent endothelial dysfunction after pregn...
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