Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia: INOVASIA study

Muhammad Ilham Aldika Akbar, Angelina Yosediputra, Raditya Ery Pratama, Nur Lailatul Fadhilah, Sulistyowati Sulistyowati, Fariska Zata Amani, Erry Gumilar Dachlan, Muhammad Dikman Angsar, Gustaaf Albert Dekker

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6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5375-5382
Number of pages8
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume35
Issue number25
DOIs
Publication statusPublished - 2022

Keywords

  • Pravastatin
  • endothelin-1 (ET-1)
  • interleukin-6 (IL-6)
  • nitric oxide (NO)
  • vascular endothelial growth factor (VEGF)

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