Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker
Background We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.020302 |
| _version_ | 1797810185714008064 |
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| author | Tess Cruickshank Teresa M. MacDonald Susan P. Walker Emerson Keenan Kirsten Dane Anna Middleton Valerie Kyritsis Jenny Myers Catherine Cluver Roxanne Hastie Lina Bergman Damanpreet Garcha Ping Cannon Elizabeth Murray Tuong‐Vi Nguyen Richard Hiscock Natasha Pritchard Natalie J. Hannan Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino |
| author_facet | Tess Cruickshank Teresa M. MacDonald Susan P. Walker Emerson Keenan Kirsten Dane Anna Middleton Valerie Kyritsis Jenny Myers Catherine Cluver Roxanne Hastie Lina Bergman Damanpreet Garcha Ping Cannon Elizabeth Murray Tuong‐Vi Nguyen Richard Hiscock Natasha Pritchard Natalie J. Hannan Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino |
| author_sort | Tess Cruickshank |
| collection | DOAJ |
| description | Background We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF‐15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt‐1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF‐15×sFlt‐1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF‐15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF‐15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF‐15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt‐1/PlGF ratio. |
| first_indexed | 2024-03-13T07:05:24Z |
| format | Article |
| id | doaj.art-66a4629a4d3e44588e70e5f1551eddcf |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-13T07:05:24Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-66a4629a4d3e44588e70e5f1551eddcf2023-06-06T12:10:51ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-08-01101610.1161/JAHA.120.020302Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease BiomarkerTess Cruickshank0Teresa M. MacDonald1Susan P. Walker2Emerson Keenan3Kirsten Dane4Anna Middleton5Valerie Kyritsis6Jenny Myers7Catherine Cluver8Roxanne Hastie9Lina Bergman10Damanpreet Garcha11Ping Cannon12Elizabeth Murray13Tuong‐Vi Nguyen14Richard Hiscock15Natasha Pritchard16Natalie J. Hannan17Stephen Tong18Tu’uhevaha J. Kaitu’u‐Lino19Translational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaThe Department of Obstetrics and Gynaecology Mercy Hospital for WomenUniversity of Melbourne AustraliaThe Department of Obstetrics and Gynaecology Mercy Hospital for WomenUniversity of Melbourne AustraliaThe Department of Obstetrics and Gynaecology Mercy Hospital for WomenUniversity of Melbourne AustraliaMercy Perinatal Mercy Hospital for Women Heidelberg Victoria AustraliaThe Department of Obstetrics and Gynaecology Mercy Hospital for WomenUniversity of Melbourne AustraliaMercy Perinatal Mercy Hospital for Women Heidelberg Victoria AustraliaSt Mary's Hospital Manchester Academic Health Science CentreUniversity of Manchester United KingdomTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaDepartment of Obstetrics and Gynecology Tygerberg Hospital Stellenbosch University Cape Town South AfricaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaThe Department of Obstetrics and Gynaecology Mercy Hospital for WomenUniversity of Melbourne AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaBackground We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF‐15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt‐1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF‐15×sFlt‐1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF‐15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF‐15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF‐15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt‐1/PlGF ratio.https://www.ahajournals.org/doi/10.1161/JAHA.120.020302biomarkerplacental growth factorpreeclampsiapregnancy |
| spellingShingle | Tess Cruickshank Teresa M. MacDonald Susan P. Walker Emerson Keenan Kirsten Dane Anna Middleton Valerie Kyritsis Jenny Myers Catherine Cluver Roxanne Hastie Lina Bergman Damanpreet Garcha Ping Cannon Elizabeth Murray Tuong‐Vi Nguyen Richard Hiscock Natasha Pritchard Natalie J. Hannan Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease biomarker placental growth factor preeclampsia pregnancy |
| title | Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker |
| title_full | Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker |
| title_fullStr | Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker |
| title_full_unstemmed | Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker |
| title_short | Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker |
| title_sort | circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis implications as a disease biomarker |
| topic | biomarker placental growth factor preeclampsia pregnancy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.020302 |
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