Department Obstetrics & Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Department Obstetrics & Gynecology, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):5375-5382. doi: 10.1080/14767058.2021.1879785. Epub 2021 Jan 31.
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).
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).
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, = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 = .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), = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), = .287).
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.
印度尼西亚 INOVASIA 研究是一项正在进行的多中心随机、开放对照试验，研究普伐他汀在被认为高危的患者中预防子痫前期的作用。在这里，我们评估普伐他汀对循环炎症和内皮标志物的影响，即血管内皮生长因子（VEGF）、白细胞介素-6（IL-6）、内皮素-1（ET-1）和一氧化氮（NO）。
根据胎儿医学基金会子痫前期筛查试验或早产子痫前期病史，或临床危险因素联合 11-20 周妊娠时子宫动脉多普勒血流模式异常，招募被认为有发生子痫前期高风险的孕妇。这是一项较大试验（INOVASIA）中的嵌套队列研究；连续招募了 38 名患者，并将其分为普伐他汀组和对照组。普伐他汀组患者在 14 至 20 周时开始服用普伐他汀（2×20mg po），同时服用标准剂量的阿司匹林（80mg po）和钙（1g po），直至分娩。在开始研究药物治疗前和分娩前（前后测试检查），连续采集血液样本以测量各种生物标志物。
在两个时间点测量各种生物标志物的样本数为：VEGF：38，IL-6：30，ET-1：38，NO：35。普伐他汀组的 IL-6 水平显著降低（均值±标准差）：（191.87±82.99 与 151.85+48.46，=0.013），而对照组的水平没有明显变化（中位数（四分位距））（144.17（53.91）与 140.82（16.18），=0.177）。普伐他汀组的 ET-1 水平显著降低（3.64±0.85 与 3.01±0.74，=0.006），而对照组的水平相对稳定（3.57±1.12 与 3.78±0.73，=0.594）。NO 是唯一在两组中都显示出显著变化的血清标志物。普伐他汀组的 NO 水平升高（11.30（17.43）与 41.90（53.18），=0.044），对照组的 NO 水平降低（38.70（34.80）与 10.03（26.96），=0.002）。VEGF 水平在两组中似乎呈现出相反的趋势（无统计学意义）（普伐他汀：3.22（0.62）与 3.28（0.75），=0.402.对照组：3.38（0.83）与 3.06（0.74），=0.287）。
给予 40mg 普伐他汀可改善 NO 水平，并降低 IL-6 和内皮素（ET-1）水平。普伐他汀对这些生物标志物的作用方向似乎支持普伐他汀在预防子痫前期中的有益作用。
