sFlt-1 Levels as an Indicator of the Effectiveness of Antihypertensive Agents in Gestational Hypertension
DOI:
https://doi.org/10.51601/ijhp.v6i3.675Abstract
Gestational hypertension is reported to increase maternal morbidity and mortality, linked to higher levels of soluble fms-like tyrosine kinase-1 (sFlt-1) that lead to endothelial dysfunction. Methyldopa and nifedipine are thought to improve the angiogenic profile, but there are limited data on the effect on the sFlt-1 levels. Therefore, this study aimed to evaluate how methyldopa alone and the combination of methyldopa with nifedipine affect sFlt-1 levels and mean arterial pressure (MAP) in cases of gestational hypertension. This prospective observational study included 30 patients with gestational hypertension who were divided into the methyldopa monotherapy (n=15) and methyldopa-nifedipine combination group (n=15). sFlt-1 levels were calculated utilizing the enzyme-linked immunosorbent assay (ELISA) method in the first 24 hours of hospitalization (prepartum) and 24 hours after delivery (postpartum). The results showed that the combination group experienced a decrease in sFlt-1 levels and MAP by 23.8% (p<0.05) and 13.1% (p<0.001), respectively. These values were greater than those of the monotherapy group, which only reduced sFlt-1 levels by 18.8% (p>0.05) and MAP by 10.4% (p<0.05). A more consistent decrease in sFlt-1 levels was observed in five patients with severe preeclampsia who received additional magnesium sulphate (MgSO₄). In conclusion, methyldopa monotherapy and the combination of methyldopa-nifedipine reduced sFlt-1 and MAP levels. This result made sFlt-1 levels a marker of the effectiveness of antihypertensive therapy in gestational hypertension.
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[1]. Herwati TW, Yulistiani Y, Eddy Zarkaty M. Analysis of methyldopa therapy on sFlt-1 antiangiogenic levels in patients with severe preeclampsia. Folia Med Indones. 2018;54(1).
[2]. Indonesian Ministry of Health. The health profile of Indonesia 2019. Jakarta: Ministry of Health Republic of Indonesia; 2020.
[3]. Zielińska J, Darmochwał-Kolarz D. A review of the diagnosis, risk factors, and role of angiogenetic factors in hypertensive disorders of pregnancy. Med Sci Monit. 2025;31:e945628. doi:10.12659/MSM.945628.
[4]. Longhitano E, Siligato R, Torreggiani M, Attini R, Masturzo B, Casula V, Matarazzo I, Cabiddu G, Santoro D, Versino E, Piccoli GB. The hypertensive disorders of pregnancy: a focus on definitions for clinical nephrologists. J Clin Med. 2022;11(12):3420. doi:10.3390/jcm11123420
[5]. Katsi V, Skalis G, Vamvakou G, Tousoulis D, Makris T. Postpartum hypertension. Curr Hypertens Rep. 2020 Aug 6;22(8):58. doi:10.1007/s11906-020-01058-w
[6]. Possomato-Vieira JS, Khalil RA. Mechanisms of endothelial dysfunction in hypertensive pregnancy and preeclampsia. Adv Pharmacol. 2016;77:361-431.doi:10.1016/bs.apha.2016.04.008
[7]. Guerby P, Tasta O, Swiader A, et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. Redox Biol. 2021 Apr;40:101861. doi:10.1016/j.redox.2021.101861
[8]. Jena MK, Sharma NR, Petitt M, Maulik D, Nayak NR. Pathogenesis of preeclampsia and therapeutic approaches targeting the placenta. Biomolecules. 2020 Jun 24;10(6):953. doi:10.3390/biom10060953
[9]. Ngene NC, Moodley J. Physiology of blood pressure relevant to managing hypertension in pregnancy. J Matern Fetal Neonatal Med. 2019 Apr;32(8):1368-1377. doi:10.1080/14767058.2017.1404569
[10]. MacDonald TM, Walker SP, Hannan NJ, Tong S, Kaitu’u-Lino TJ. Clinical tools and biomarkers to predict preeclampsia. EBioMedicine. 2022;75:103780. doi:10.1016/j.ebiom.2021.103780
[11]. Nunes PR, Bruder RM, Kaihara JNS, de Moraes FR, Tasic L, Bernardino RL, et al. Endothelial responses to angiogenic modulators in preeclampsia. Placenta. 2025;171:178–187. doi:10.1016/j.placenta.2025.09.018
[12]. Dragan I, Wright D, Fiolna M, Leipold G, Nicolaides KH. Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio >38: comparison of performance at 31-34 vs 35-37 weeks' gestation. Ultrasound Obstet Gynecol. 2017 Feb;49(2):209-12. doi:10.1002/uog.17310
[13]. Zeisler H, Llurba E, Chantraine F, et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. New England Journal of Medicine. 2016;374(1):13–22. DOI: 10.1056/NEJMoa1414838
[14]. Tamargo J. Selecting emergency therapy for patients with pre-eclampsia. Expert Opin Pharmacother. 2020;21(10):1119-1122. doi:10.1080/14656566.2020.1727444.
[15]. Wen J, Li X. Effect of magnesium sulfate combined with phentolamine and nifedipine for gestational hypertension and serum levels of LIF and apelin. J Coll Physicians Surg Pak. 2019;29(3):231-234. doi:10.29271/jcpsp.2019.03.231.
[16]. Khalil A, Muttukrishna S, Harrington K, Jauniaux E. Effect of antihypertensive therapy with alpha methyldopa on angiogenic factors in hypertensive pregnancies. PLoS One. 2008;3(7):e2766.doi:10.1371/journal.pone.0002766
[17]. Shen X, Yan J, Ren A. Effect of long-acting nifedipine on blood pressure level, eutocia rate and neonatal health status in patients with pregnancy-induced hypertension. Int J Clin Exp Med. 2019;12(3):2605-2611
[18]. Indonesian Heart Association. Guidelines for the management of cardiovascular disease in pregnancy. Jakarta: Indonesian Heart Association; 2021.
[19]. American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia. Obstet Gynecol. 2020;135(6):222
[20]. Perhimpunan Obstetri dan Ginekologi Indonesia (POGI). Pedoman klinis untuk operasi caesar. Jakarta: Perhimpunan Obstetri dan Ginekologi Indonesia; 2016.
[21]. Namazov A, Grin L, Karakus R, Uludogan M, Ayvaci H. Effect of maternal nifedipine therapy on fetoplacental blood flow. Arch Gynecol Obstet. 2018;298(4):685–688. doi:10.1007/s00404-018-4839-9
[22]. Wang Y, Bao J, Peng M. Effect of magnesium sulfate combined with labetalol on serum sFlt-1/PlGF ratio in early-onset severe preeclampsia. Exp Ther Med. 2020;20:276. doi:10.3892/etm.2020.9406
[23]. Saleh L, van den Meiracker AH, Geensen R, Kaya A, Roeters van Lennep JE, Duvekot JJ, Verdonk K, Steegers EAP, Russcher H, Danser AHJ, Visser W. Soluble fms-like tyrosine kinase-1 and placental growth factor kinetics during and after pregnancy in women with suspected or confirmed pre-eclampsia. Ultrasound Obstet Gynecol. 2018 Jun;51(6):751-7. doi:10.1002/uog.17547.
[24]. Lykou D, Kirk M, Koulouraki S, Rode L, Andersson M, Hansson E, et al. Evaluation of dynamic patterns of sFlt-1, PlGF and their ratio in maternal plasma from diagnosis to postpartum as a new tool for preeclampsia management. Hypertens Pregnancy. 2025;44(1):2579976. doi:10.1080/10641955.2025.2579976.
[25]. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and risk of preeclampsia. N Engl J Med. 2004;350(7):672–683. doi:10.1056/NEJMoa031884
[26]. Ngene NC, Moodley J. Physiology of blood pressure relevant to managing hypertension in pregnancy. J Matern Fetal Neonatal Med. 2019 Apr;32(8):1368-1377. doi:10.1080/14767058.2017.1404569
[27]. Tomimatsu T, Mimura K, Matsuzaki S, Endo M, Kumasawa K, Kimura T. Preeclampsia: maternal systemic vascular disorder caused by generalized endothelial dysfunction due to placental antiangiogenic factors. Int J Mol Sci. 2019 Aug 30;20(17):4246. doi:10.3390/ijms20174246
[28]. American College of Obstetricians and Gynecologists. Chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):203
[29]. Lopes Perdigao J, Chinthala S, Mueller A, Minhas R, Ramadan H, Nasim R, Naseem H, Young D, Shahul S, Chan SL, Yeo KJ, Rana S. Angiogenic factor estimation as a warning sign of preeclampsia-related peripartum morbidity among hospitalized patients. Hypertension. 2019Apr;73(4):868-877. doi:10.1161/HYPERTENSIONAHA.118.12205
[30]. Minhas R, Young D, Naseem R, Mueller A, Chinthala S, Perdigao JL, Yeo KJ, Chan SL, Tung A, White JB, Shahul S, Rana S. Association of antepartum blood pressure levels and angiogenic profile among women with chronic hypertension. Pregnancy Hypertens. 2018 Oct;14:110-114. doi:10.1016/j.preghy.2018.09.003
[31]. Awaludin A, Rahayu C, Daud NAA, Zakiyah N. Antihypertensive medications for severe hypertension in pregnancy: a systematic review and meta-analysis. Healthcare (Basel). 2022 Feb 9;10(2):325. doi:10.3390/healthcare10020325
[32]. Pangkahila E, Saspriyana KY, Amanda C, Septiani W. Effect of magnesium sulfate (MgSO4) on nitric oxide and prostacyclin levels in preeclampsia. Andalas Obstet Gynecol J. 2025;9(1):1–15. doi:10.25077/aoj.9.1.1-15.2025.
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