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High-Sensitivity Cardiac Troponin I Enhances Preeclampsia Prediction Beyond Maternal Factors and the sFlt-1/PlGF
Lucas Bacmeister1, Alina Goßling2, Annette Buellesbach1
1Clinic for Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany (L.B., A. Buellesbach, D.W.).
Insights
High-sensitivity cardiac troponin I (hs-cTnI) shows promise in predicting preeclampsia, especially preterm preeclampsia. This cardiac biomarker may enhance existing prediction models or serve as an alternative where angiogenic biomarkers are unavailable.
Area of Science:
- Cardiovascular Medicine
- Obstetrics and Gynecology
- Biomarker Discovery
Background:
- Preeclampsia shares risk factors with cardiovascular diseases.
- High-sensitivity cardiac troponin I (hs-cTnI) is a potential biomarker for cardiovascular health.
- The utility of hs-cTnI in predicting preeclampsia requires investigation.
Purpose of the Study:
- To assess the predictive value of hs-cTnI levels during pregnancy for preeclampsia occurrence.
- To evaluate hs-cTnI as a potential biomarker for preeclampsia, particularly preterm preeclampsia.
- To compare the performance of hs-cTnI with established angiogenic biomarkers in preeclampsia prediction models.
Main Methods:
- Measured hs-cTnI levels in 2245 pregnant women across 4 international prospective cohorts.
- Employed cross-sectional, longitudinal, and predictive modeling analyses.
- Incorporated hs-cTnI, maternal factors, and the sFlt-1/PlGF ratio in prediction models.
Main Results:
- Elevated hs-cTnI levels were associated with higher odds of preeclampsia, particularly preterm preeclampsia (OR, 5.78).
- A prediction model with hs-cTnI and maternal factors showed comparable performance to the sFlt-1/PlGF ratio.
- A comprehensive model including hs-cTnI, sFlt-1/PlGF, and maternal factors improved prediction accuracy (AUC, 0.78).
Conclusions:
- hs-cTnI shows potential as a complementary biomarker for preeclampsia prediction.
- hs-cTnI may substitute for or enhance existing prediction models, especially in resource-limited settings.
- Further validation in prospective studies is warranted to establish hs-cTnI's clinical utility.
Background:
Preeclampsia shares numerous risk factors with cardiovascular diseases. Here, we aimed to assess the potential utility of high-sensitivity cardiac troponin I (hs-cTnI) values during pregnancy in predicting preeclampsia occurrence.
Methods:
This study measured hs-cTnI levels in 3721 blood samples of 2245 pregnant women from 4 international, prospective cohorts. Three analytical approaches were used: (1) a cross-sectional analysis of all women using a single blood sample, (2) a longitudinal analysis of hs-cTnI trajectories in women with multiple samples, and (3) analyses of prediction models incorporating hs-cTnI, maternal factors, and the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio.
Results:
Women with hs-cTnI levels in the upper quarter had higher odds ratios for preeclampsia occurrence compared with women with levels in the lower quarter. Associations were driven by preterm preeclampsia (odds ratio, 5.78 [95% CI, 2.73-12.26]) and remained significant when using hs-cTnI as a continuous variable adjusted for confounders. Between-trimester hs-cTnI trajectories were independent of subsequent preeclampsia occurrence. A prediction model incorporating a practical hs-cTnI level of detection cutoff (≥1.9 pg/mL) alongside maternal factors provided comparable performance with the sFlt-1/PlGF ratio. A comprehensive model including sFlt-1/PlGF, maternal factors, and hs-cTnI provided added value (cross-validated area under the receiver operator characteristic, 0.78 [95% CI, 0.73-0.82]) above the sFlt-1/PlGF ratio alone (cross-validated area under the receiver operator characteristic, 0.70 [95% CI, 0.65-0.76]; P=0.027). As assessed by likelihood ratio tests, the addition of hs-cTnI to each prediction model significantly improved the respective prediction model not incorporating hs-cTnI, particularly for preterm preeclampsia. Net reclassification improvement analyses indicated that incorporating hs-cTnI improved risk prediction predominantly by correctly reclassifying women with subsequent preeclampsia occurrence.
Conclusions:
These exploratory findings uncover a potential role for hs-cTnI as a complementary biomarker in the prediction of preeclampsia. After validation in prospective studies, hs-cTnI, alongside maternal factors, may either be considered as a substitute for angiogenic biomarkers in health care systems where they are sparce or unavailable, or as an enhancement to established prediction models using angiogenic markers.
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