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
1
Systematic Review and Meta-analysis on Non-classic Cardiovascular Biomarkers
2
after Hypertensive Pregnancy Disorders
3 Sanne VISSER1,2, Wietske HERMES, MD1,3, Johannes C.F. KET4, René. H.J. OTTEN4, Maria G.
5
VAN PAMPUS, M., PhD.2, Kitty W.M. BLOEMENKAMP, M.,PhD.6,
6
Arie FRANX, MD,PhD.5, Ben W. MOL, MD.,PhD.7, Christianne J.M. DE GROOT, MD,PhD1.
RI PT
4
7
1. Obstetrics and Gynecology, VU University Medical Center, Amsterdam
9
2. Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis, Amsterdam
SC
8
3. Obstetrics and Gynecology, Medical Center Haaglanden, the Hague
11
4. Medical Library, VU University, Amsterdam
12
5. Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht
13
6. Obstetrics and Gynecology, Leiden University Medical Center, Leiden
14
7. Obstetrics and Gynecology, Amsterdam Medical Center, Amsterdam
M AN U
10
15 16
Supported by a grant from Nuts Ohra Foundation, the Netherlands
17
Corresponding author: Sanne Visser, MD, Onze Lieve Vrouwe Gasthuis, Department of
19
Obstetrics and Gynecology, Oosterpark 9, 1091 AC Oost en Watergraafsmeer, Amsterdam,
20
The Netherlands; phone: +31 020 5999111, e-mail: [email protected].
22
Word Count: 250 (abstract) / 3794 (main text)
24 25 26 27 28
Disclosure Statement: The authors report no conflict of interest.
AC C
23
EP
21
TE D
18
29 30 31 32 1
ACCEPTED MANUSCRIPT
33
CONDENSATION
34
Women with a history of hypertensive pregnancy disorders have significant elevated
35
homocysteine levels and increased levels of biomarkers in areas of inflammation, thrombosis
36
and angiogenesis.
38
RI PT
37 Short Title: Cardiovascular Risk after Pregnancy
39 40
SC
41 42 43
M AN U
44 45 46 47 48 49
TE D
50 51 52
55 56 57 58 59 60
AC C
54
EP
53
61 62 63 64 2
ACCEPTED MANUSCRIPT
ABSTRACT
66
Objective: The aim of this study is to investigate which non-classic cardiovascular biomarkers
67
are associated with persistent endothelial dysfunction after pregnancy in women with a
68
history of hypertensive pregnancy disorders compared to women with uncomplicated
69
pregnancies.
70
Study design: Systematic review and meta-analysis of observational studies.
71
A search was performed in PubMed, Embase, Cochrane and Cinahl including articles from
72
inception to 27 February 2013. Included were cohort studies and case-control studies. Cases
73
were women with a history of hypertension in pregnancy, control subjects were women with
74
a history of uncomplicated pregnancies.
75
Of the 3136 found, 21 studies on 16 non-classic cardiovascular biomarkers are described in
76
this review; 12 studies on 5 biomarkers were included in the meta-analysis.
77
Results: Women with a history of hypertensive pregnancy disorders had a higher
78
homocysteine level compared to women with a history of uncomplicated pregnancies (5
79
studies; pooled mean difference 0.77ng/ml; 95% confidence interval 0.27 to 1.26; p 1 (20months)
Homocysteine (means)
168
Mean: 7.8
Homocysteine (means) IL-6, PAI-1, TNF-α (medians)
18
17
1 (15months)
Fibrinogen, VWF, tPA ICAM, VCAM, E-selectin (means) PAI-1(medians)
340
113
0.5 (>6months)
Fibrinogen, IL-6, ICAM, VWF (means)
28
20
Range:5-6
IL-6, VWF (medians)
PT + T
65
54
Mean: 6
PAI-1 (means) Ddimer, Fibrinogen, tPA (medians)
PT+T
58
49
Mean: 6
VCAM, ICAM (means)
Not reported
Not reported
16
17
Median: 4
Homocysteine (means)
Not reported
Not reported
37
37
0.5 (6months)
TNFα (medians)
PT+T
16
18
Median:9.4 (cases) 9.7 (controls)
sFlt , VEGF, E-selectin(medians)
EP
TE D
M AN U
SC
168 63 +105
AC C
Cases 22.8 Controls 40.2
*Studies included in meta-analyses
2
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
1
Systematic Review and Meta-analysis on Non-classic Cardiovascular Biomarkers
2
after Hypertensive Pregnancy Disorders
3 Sanne VISSER1,2, Wietske HERMES, MD1,3, Johannes C.F. KET4, René. H.J. OTTEN4, Maria G.
5
VAN PAMPUS, M., PhD.2, Kitty W.M. BLOEMENKAMP, M.,PhD.6,
6
Arie FRANX, MD,PhD.5, Ben W. MOL, MD.,PhD.7, Christianne J.M. DE GROOT, MD,PhD1.
RI PT
4
7
1. Obstetrics and Gynecology, VU University Medical Center, Amsterdam
9
2. Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis, Amsterdam
SC
8
3. Obstetrics and Gynecology, Medical Center Haaglanden, the Hague
11
4. Medical Library, VU University, Amsterdam
12
5. Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht
13
6. Obstetrics and Gynecology, Leiden University Medical Center, Leiden
14
7. Obstetrics and Gynecology, Amsterdam Medical Center, Amsterdam
M AN U
10
15 16
Supported by a grant from Nuts Ohra Foundation, the Netherlands
17
Corresponding author: Sanne Visser, MD, Onze Lieve Vrouwe Gasthuis, Department of
19
Obstetrics and Gynecology, Oosterpark 9, 1091 AC Oost en Watergraafsmeer, Amsterdam,
20
The Netherlands; phone: +31 020 5999111, e-mail: [email protected].
22
Word Count: 250 (abstract) / 3794 (main text)
24 25 26 27 28
Disclosure Statement: The authors report no conflict of interest.
AC C
23
EP
21
TE D
18
29 30 31 32 1
ACCEPTED MANUSCRIPT
33
CONDENSATION
34
Women with a history of hypertensive pregnancy disorders have significant elevated
35
homocysteine levels and increased levels of biomarkers in areas of inflammation, thrombosis
36
and angiogenesis.
38
RI PT
37 Short Title: Cardiovascular Risk after Pregnancy
39 40
SC
41 42 43
M AN U
44 45 46 47 48 49
TE D
50 51 52
55 56 57 58 59 60
AC C
54
EP
53
61 62 63 64 2
ACCEPTED MANUSCRIPT
ABSTRACT
66
Objective: The aim of this study is to investigate which non-classic cardiovascular biomarkers
67
are associated with persistent endothelial dysfunction after pregnancy in women with a
68
history of hypertensive pregnancy disorders compared to women with uncomplicated
69
pregnancies.
70
Study design: Systematic review and meta-analysis of observational studies.
71
A search was performed in PubMed, Embase, Cochrane and Cinahl including articles from
72
inception to 27 February 2013. Included were cohort studies and case-control studies. Cases
73
were women with a history of hypertension in pregnancy, control subjects were women with
74
a history of uncomplicated pregnancies.
75
Of the 3136 found, 21 studies on 16 non-classic cardiovascular biomarkers are described in
76
this review; 12 studies on 5 biomarkers were included in the meta-analysis.
77
Results: Women with a history of hypertensive pregnancy disorders had a higher
78
homocysteine level compared to women with a history of uncomplicated pregnancies (5
79
studies; pooled mean difference 0.77ng/ml; 95% confidence interval 0.27 to 1.26; p 1 (20months)
Homocysteine (means)
168
Mean: 7.8
Homocysteine (means) IL-6, PAI-1, TNF-α (medians)
18
17
1 (15months)
Fibrinogen, VWF, tPA ICAM, VCAM, E-selectin (means) PAI-1(medians)
340
113
0.5 (>6months)
Fibrinogen, IL-6, ICAM, VWF (means)
28
20
Range:5-6
IL-6, VWF (medians)
PT + T
65
54
Mean: 6
PAI-1 (means) Ddimer, Fibrinogen, tPA (medians)
PT+T
58
49
Mean: 6
VCAM, ICAM (means)
Not reported
Not reported
16
17
Median: 4
Homocysteine (means)
Not reported
Not reported
37
37
0.5 (6months)
TNFα (medians)
PT+T
16
18
Median:9.4 (cases) 9.7 (controls)
sFlt , VEGF, E-selectin(medians)
EP
TE D
M AN U
SC
168 63 +105
AC C
Cases 22.8 Controls 40.2
*Studies included in meta-analyses
2
