Journal
HYPERTENSION
Volume 63, Issue 2, Pages 346-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.113.01787
Keywords
angiogenesis; angiogenic factors; antiangiogenic factors; hypertension; preeclampsia; pregnancy; sFlt1-PlGF ratio
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Funding
- Roche Diagnostics, Germany
- [RVO-VFN64165/2012]
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To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at <= 33 and >= 85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of <= 33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values >= 85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at <= 33 and >= 110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.
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