TY - JOUR
T1 - Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia
T2 - INOVASIA study
AU - Akbar, Muhammad Ilham Aldika
AU - Yosediputra, Angelina
AU - Pratama, Raditya Ery
AU - Fadhilah, Nur Lailatul
AU - Sulistyowati, Sulistyowati
AU - Amani, Fariska Zata
AU - Dachlan, Erry Gumilar
AU - Dikman Angsar, Muhammad
AU - Dekker, Gustaaf Albert
N1 - Funding Information:
We thank Prof. Dr. Hendy Hendarto dr. SpOG(K) as the head of the department who supports and permits to perform this study. We thank Prof. Chris Redman MB, BChir, FRCP, FRCOG, (emeritus) for his contribution and advice in writing and increasing the quality of this manuscript. We thank all staff in the Department Obstetrics & Gynecology Faculty of Medicine Universitas Airlangga–RSUD Dr. Soetomo–RS UNAIR for their genuine support for this study. We thank our resident in training and the research team for their hard work in collecting data in this study; and we would like to thank all the patients who were involved in this study, without their participation the study could never be completed.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Introduction: The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO). Methods: Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11–20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination). Result: The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p =.013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p =.177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p =.006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p =.594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p =.044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p =.002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p =.402. Control: 3.38 (0.83) vs. 3.06 (0.74), p =.287). Conclusion: Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.
AB - Introduction: The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO). Methods: Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11–20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination). Result: The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p =.013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p =.177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p =.006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p =.594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p =.044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p =.002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p =.402. Control: 3.38 (0.83) vs. 3.06 (0.74), p =.287). Conclusion: Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.
KW - Pravastatin
KW - endothelin-1 (ET-1)
KW - interleukin-6 (IL-6)
KW - nitric oxide (NO)
KW - vascular endothelial growth factor (VEGF)
UR - http://www.scopus.com/inward/record.url?scp=85100187445&partnerID=8YFLogxK
U2 - 10.1080/14767058.2021.1879785
DO - 10.1080/14767058.2021.1879785
M3 - Article
AN - SCOPUS:85100187445
SN - 1476-7058
VL - 35
SP - 5375
EP - 5382
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 25
ER -