The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review

References

• Minsker DH, MacDonald JS, Robertson RT, et al. Mevalonate supplementation in pregnant rats suppresses the teratogenicity of mevinolinic acid, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase. Teratology. 1983;28(3):449–456.
   PubMedGoogle Scholar
• Dostal LA, Schardein JL, Anderson JA. Developmental toxicity of the HMG-CoA reductase inhibitor, atorvastatin, in rats and rabbits. Teratology. 1994;50(6):387–394.
   PubMedGoogle Scholar
• Ghidini A, Sicherer S, Willner J. Congenital abnormalities (VATER) in baby born to mother using lovastatin. Lancet. 1992;339(8806):1416–1417.
   PubMed Web of Science ®Google Scholar
• Karalis DG, Hill AN, Clifton S, et al. The risks of statin use in pregnancy: a systematic review. J Clin Lipidol. 2016;10:1081–1090.
   PubMed Web of Science ®Google Scholar
• Zarek J, Koren G. The fetal safety of statins: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2014;36(5):506–509.
   PubMedGoogle Scholar
• Department of Health & Human Services, F., Highlights of prescribing information: altroprev (lovastatin extended-release) Tablets. 2012. p. 20.
   Google Scholar
• Marrs CC, Costantine MM. Should we add pravastatin to aspirin for preeclampsia prevention in high-risk women? Clin Obstet Gynecol. 2016;60(1):161-168.
   Web of Science ®Google Scholar
• Eunice Kennedy Shriver Natl Inst, Costantine MM, Cleary K. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol. 2013;121(2):349–353.
   PubMed Web of Science ®Google Scholar
• Lefkou E, Mamopoulos A, Dagklis T, et al. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy. J Clin Invest. 2016;126(8):2933–2940.
   PubMed Web of Science ®Google Scholar
• Napoli C, Glass CK, Witztum JL, et al. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: fate of early lesions in children (FELIC) study. Lancet. 1999;354(9186):1234–1241.
   PubMed Web of Science ®Google Scholar
• Leiva A, Salsoso R, Sáez T, et al. Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation. Placenta. 2015;36(8):895–902.
   PubMed Web of Science ®Google Scholar
• Leiva A, De Medina CD, Salsoso R, et al. Maternal hypercholesterolemia in pregnancy associates with umbilical vein endothelial dysfunction: role of endothelial nitric oxide synthase and arginase II. Arterioscler Thromb Vasc Biol. 2013;33(10):2444–2453.
   PubMed Web of Science ®Google Scholar
• Catov JM, Bodnar LM, Kip KE, et al. Early pregnancy lipid concentrations and spontaneous preterm birth. Am J Obstet Gynecol. 2007;197(6):610.e1-7.
   PubMed Web of Science ®Google Scholar
• Spracklen CN, Smith CJ, Saftlas AF, et al. Maternal hyperlipidemia and the risk of preeclampsia: a meta-analysis. Am J Epidemiol. 2014;180(4):346–358.
   PubMed Web of Science ®Google Scholar
• Costantine MM, Ananth CV. The early developments of preeclampsia drugs. Expert Opin Investig Drugs. 2016;25(8):867–870.
   PubMed Web of Science ®Google Scholar
• Tadjuidje E, Hollemann T. Cholesterol homeostasis in development: the role of Xenopus 7-dehydrocholesterol reductase (Xdhcr7) in neural development. Dev Dyn. 2006;235(8):2095–2110.
   PubMed Web of Science ®Google Scholar
• Riobo NA. Cholesterol and its derivatives in Sonic Hedgehog signaling and cancer. Curr Opin Pharmacol. 2012;12(6):736–741.
   PubMed Web of Science ®Google Scholar
• Beverly BEJ, Lambright CS, Furr JR, et al. Simvastatin and dipentyl phthalate lower ex vivo testicular testosterone production and exhibit additive effects on testicular testosterone and gene expression via distinct mechanistic pathways in the fetal rat. Toxicol Sci. 2014;141(2):524–537.
   PubMed Web of Science ®Google Scholar
• Hanaka S, Abe T, Itakura H, et al. Gene expression related to cholesterol metabolism in mouse brain during development. Brain Dev. 2000;22(5):321–326.
   PubMed Web of Science ®Google Scholar
• Wolf G. The function of cholesterol in embryogenesis. J Nutr Biochem. 1999;10(4):188–192.
   PubMed Web of Science ®Google Scholar
• Roux C, Wolf C, Mulliez N, et al. Role of cholesterol in embryonic development. Am J Clin Nutr. 2000;71(5 Suppl):1270s–9s.
   PubMed Web of Science ®Google Scholar
• Signore IA, Jerez C, Figueroa D, et al. Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish. Birth Defects Res A Clin Mol Teratol. 2016;106(10):814–830.
   PubMedGoogle Scholar
• Forbes K, Shah VK, Siddals K, et al. Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. Mol Hum Reprod. 2015;21(1):105–114.
   PubMed Web of Science ®Google Scholar
• Kusters DM, Hassani Lahsinoui H, Van De Post JAM, et al. Statin use during pregnancy: a systematic review and meta-analysis. Expert Rev Cardiovasc Ther. 2012;10(3):363–378.
   PubMedGoogle Scholar
• Morton S, Thangaratinam S. Statins in pregnancy. Curr Opin Obstet Gynecol. 2013;25(6):433–440.
   PubMed Web of Science ®Google Scholar
• Rynn L, Cragan J, Correa A. Update on overall prevalence of major birth defects — Atlanta, Georgia, 1978–2005. Center for Disease Control (CDC); MMWR. 2008;57(1):1-5.
   Google Scholar
• Taguchi N, Rubin ET, Hosokawa A, et al. Prenatal exposure to HMG-CoA reductase inhibitors: effects on fetal and neonatal outcomes. Reprod Toxicol. 2008;26(2):175–177.
   PubMed Web of Science ®Google Scholar
• Yu Z, Han S, Zhu J, et al. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS One. 2013;8(4):e61627.
   PubMed Web of Science ®Google Scholar
• Seghieri G, Anichini R, De Bellis A, et al. Relationship between gestational diabetes mellitus and low maternal birth weight. Diabetes Care. 2002;25(10):1761–1765.
   PubMed Web of Science ®Google Scholar
• Costantine MM, Zhang Z, Rosenblatt K, et al. Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol. 2016;214(6):720.e1-720.e17.
   Web of Science ®Google Scholar
• The University of Texas Medical Branch, G., Pravastatin for the Prevention of Preeclampsia in High-Risk Women: A Phase I Pilot Study | ClinicalTrials.gov ID: NCT01717586. 2016, University of Texas, University of Pittsburgh, Northwestern University.
   Google Scholar
• Ahmed A, Statins to Ameliorate early onset Pre-eclampsia | EudraCT nr: 2009-012968-13. 2014, Aston University.
   Google Scholar
• Ramma W, Ahmed A. Therapeutic potential of statins and the induction of heme oxygenase-1 in preeclampsia. J Reprod Immunol. 2014;101-102(1):153–160.
   PubMedGoogle Scholar
• Luttun A, Carmeliet P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Invest. 2003;111(5):600–602.
   PubMed Web of Science ®Google Scholar
• Kendall RL, Wang G, Thomas KA. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun. 1996;226(2):324–328.
   PubMed Web of Science ®Google Scholar
• Gallo DM, Wright D, Casanova C, et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19–24 weeks’ gestation. Am J Obstet Gynecol. 2016;214(5):619.e1–619.e17.
   PubMed Web of Science ®Google Scholar
• Tsiakkas A, Saiid Y, Wright A, et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30–34 weeks’ gestation. Am J Obstet Gynecol. 2016;215(1):87.e1–87.e17.
   PubMed Web of Science ®Google Scholar
• Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–649.
   PubMed Web of Science ®Google Scholar
• Girardi G. Can statins prevent pregnancy complications? J Reprod Immunol. 2014;101-102(1):161–167.
   PubMedGoogle Scholar
• Costantine MM, Tamayo E, Lu F, et al. Using pravastatin to improve the vascular reactivity in a mouse model of soluble fms-like tyrosine kinase-1-induced preeclampsia. Obstet Gynecol. 2010;116(1):114–120.
   PubMed Web of Science ®Google Scholar
• Fox K, Longo M, Tamayo E, et al. Pravastatin upregulates eNOS activity in the sFLT-1 mouse model of preeclampsia. Am J Obstet Gynecol. 2011;204:S23–S23.
   PubMed Web of Science ®Google Scholar
• Carver AR, Tamayo E, Perez-Polo JR, et al. The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia. Int J Dev Neurosci. 2014;33:33–40.
   PubMed Web of Science ®Google Scholar
• Carver A, Tamayo E, Gamble P, et al. Maternal pravastatin therapy prevents altered brain development of the offspring in a murine model of preeclampsia. Am J Obstet Gynecol. 2014;210(1):S25–S26.
   Web of Science ®Google Scholar
• Ekwo EE, Gosselink CA, Moawad A. Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy. Obstet Gynecol. 1992;80(2):166–172.
   PubMed Web of Science ®Google Scholar
• Banach M, Mikhailidis DP, Kjeldsen SE, et al. Time for new indications for statins? Med Sci Monit. 2009;15(12):MS1–5.
   PubMed Web of Science ®Google Scholar
• Banach M, Serban C, Ursoniu S, et al. Statin therapy and plasma coenzyme Q10 concentrations–A systematic review and meta-analysis of placebo-controlled trials. Pharmacol Res. 2015;99:329–336.
   PubMed Web of Science ®Google Scholar
• Abo-Elmatty DM, Badawy EA, Hussein JS, et al. Role of heme oxygenase, leptin, coenzyme Q10 and trace elements in pre-eclamptic women. Indian J Clin Biochem. 2012;27(4):379–384.
   PubMedGoogle Scholar
• Teran E, Racines-Orbe M, Vivero S, et al. Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels. Free Radic Biol Med. 2003;35(11):1453–1456.
   PubMed Web of Science ®Google Scholar
• Teran E, Vivero S, Racines-Orbe M, et al. Coenzyme Q10 is increased in placenta and cord blood during preeclampsia. Biofactors. 2005;25(1–4):153–158.
   PubMed Web of Science ®Google Scholar
• Palan PR, Shaban DW, Martino T, et al. Lipid-soluble antioxidants and pregnancy: maternal serum levels of coenzyme Q10, alpha-tocopherol and gamma-tocopherol in preeclampsia and normal pregnancy. Gynecol Obstet Invest. 2004;58(1):8–13.
   PubMed Web of Science ®Google Scholar
• Teran E, Hernandez I, Nieto B, et al. Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Int J Gynaecol Obstet. 2009;105(1):43–45.
   PubMed Web of Science ®Google Scholar
• Poorolajal J, Jenabi E. The association between body mass index and preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med. 2016;29(22):3670–3676.
   PubMed Web of Science ®Google Scholar
• Canto-Cetina T, Coral-Vázquez RM, Rojano-Mejía D, et al. Higher prepregnancy body mass index is a risk factor for developing preeclampsia in Maya-Mestizo women: a cohort study. Ethn Health. 2017;1–9.
   PubMedGoogle Scholar
• Gostynski M, Gutzwiller F, Kuulasmaa K, et al. Analysis of the relationship between total cholesterol,age, body mass index among males and females in theWHO MONICA project. Int J Obes. 2004;28(8):1082–1090.
   Web of Science ®Google Scholar
• Sheng X, Murphy MJ, MacDonald TM, et al. Effect of statins on total cholesterol concentrations and cardiovascular outcomes in patients with diabetes mellitus: a population-based cohort study. Eur J Clin Pharmacol. 2012;68(8):1201–1208.
   PubMed Web of Science ®Google Scholar
• Barter PJ, Brandrup-Wognsen G, Palmer MK, et al. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER database. J Lipid Res. 2010;51(6):1546–1553.
   PubMed Web of Science ®Google Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Circulation. 2014;129:S1–S45SS1–S45.
   Web of Science ®Google Scholar
• Sauser K, Levine DA, Hayward RA. A review of the clinical evidence related to early treatment of elevated LDL for cardiovascular primary prevention. Evid Based Med. 2015;20(5):162–169.
   PubMedGoogle Scholar
• Hermes W, Tamsma JT, Grootendorst DC, et al. Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study. BMC Pregnancy Childbirth. 2013;13(126):1–11.
   PubMedGoogle Scholar
• De Vera MA, Choi H, Abrahamowicz M, et al. Statin discontinuation and risk of acute myocardial infarction in patients with rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis. 2011;70(6):1020–1024.
   PubMed Web of Science ®Google Scholar
• Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2016;37(11):908–916.
   PubMed Web of Science ®Google Scholar
• Gomez Sandoval YH, Braganza MV, Daskalopoulou SS. Statin discontinuation in high-risk patients: a systematic review of the evidence. Curr Pharm Des. 2011;17(33):3669–3689.
   PubMed Web of Science ®Google Scholar
• Frantz E, Menezes HS, Lange KC, et al. The effect of maternal hypercholesterolemia on the placenta and fetal arteries in rabbits. Acta Cir Bras. 2012;27(1):7–12.
   PubMed Web of Science ®Google Scholar
• Napoli C, D’Armiento FP, Mancini FP, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. J Clin Invest. 1997;100(11):2680–2690.
   PubMed Web of Science ®Google Scholar
• Martino F, Magenta A, Pannarale G, et al. Epigenetics and cardiovascular risk in childhood. J Cardiovasc Med. 2016;17:539–546.
   Google Scholar
• Wild R, Weedin EA, Wilson D. Dyslipidemia in pregnancy. Endocrinol Metab Clin N Am. 2016;45:55–63.
   PubMed Web of Science ®Google Scholar
• France M, Rees A, Datta D, et al. HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom. Atherosclerosis. 2016;255:128–139.
   PubMed Web of Science ®Google Scholar
• Fischer S, Julius U. Management of patients with statin intolerance. Atheroscler Suppl. 2017;30:33–37.
   PubMed Web of Science ®Google Scholar
• Nicolaides K, Randomised Controlled Trial with Pravastatin versus Placebo for PreventIon of Pre-eclampsia | Eudract No. 2015-005130-22 | ISRCTN No. ISRCTN17787139. 2016, Fundación para la Formación e Investigación Sanitaria (FFIS).
   Google Scholar
• Kim EN, Yoon BH, Jeon EJ, et al. Placental deposition of C-reactive protein is a common feature of human pregnancy. Placenta. 2015;36:704–707.
   PubMed Web of Science ®Google Scholar
• Udenze I, Amadi C, Awolola N, et al. The role of cytokines as inflammatory mediators in preeclampsia. Pan Afr Med J. 2015;20(219).
   PubMedGoogle Scholar
• Asher J, Houston M. Statins and C-reactive protein levels. J Clin Hypertens. 2007;9(8):622–628.
   Google Scholar
• Banach M, Rizzo M, Toth PP, et al. Statin intolerance - an attempt at a unified definition. Position paper from an international lipid expert panel. Arch Med Sci. 2015;11(1):1–23.
   PubMed Web of Science ®Google Scholar
• Banach M, Aronow WS, Serban M-C, et al. Lipids, blood pressure and kidney update 2015. Lipids Health Dis. 2015;14:167.
   PubMed Web of Science ®Google Scholar
• Rosenson RS, Baker S, Banach M, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70(10):1290–1301.
   PubMed Web of Science ®Google Scholar
• Hobbs FD, Banach M, Mikhailidis DP, et al. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate. BMC Med. 2016;14:4.
   Web of Science ®Google Scholar