Hypercholesterolemia During Pregnancy is Caused by Increased Endogenous Cholesterol Synthesis: Let's Use it for Screening of Familial Hypercholesterolemias Too!

Authors

  • Josef Hyánek Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague
  • František Pehal Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague
  • Ladislava Dubská Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague
  • Blanka Míková Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague
  • Lada Gombíková Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague
  • Stanislav Kubu Department of Clinical Biochemistry, Central Laboratories, Institute for the Care of Mother and Child, Prague
  • Petra Halácková Department of Clinical Biochemistry, Central Laboratories, Institute for the Care of Mother and Child, Prague
  • Jaroslav Feyreisl Department of Clinical Biochemistry, Central Laboratories, Institute for the Care of Mother and Child, Prague
  • Ludek Táborský Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague

DOI:

https://doi.org/10.6000/1929-5634.2017.06.04.1

Keywords:

Hypercholesterolemia during pregnancy, familial hypercholesterolemia, non-cholesterol sterols, lathosterol, desmosterol, campesterol, sitosterol.

Abstract

Abstract: Aims: To demonstrate the origin and the diagnostic significance of non-cholesterol sterols (NCSs) in healthy pregnant women with gestational hypercholesterolemia.

Patients and Methods: Based on a total of 21,000 clinical biochemistry tests of healthy pregnant women with hypercholesterolemia observed during pregnancy, a group of 84 women with TC (total cholesterol) >7.0 mmol/L was recruited to analyze their NCSs using Gas Chromatography–Mass Spectrometry. The NCSs under examination comprised lathosterol (Lat) and desmosterol (Des) as markers of endogenous cholesterol synthesis, and campesterol (Cam) and sitosterol (Sit) as markers for intestinal absorption.

Results: In the total of 21,000 pregnant women, the median values were: TC 6.8 mol/l, LDL-C 4.6 mmol/L, and HDL-C 2.2 mmol/L. In the testing group of 84 women, the average values were: Lat 7.8+/-1.7 μmol/L, Des 4.7+/-0.9 μmol/L, Cam 9.8+/-2.6 μmol/L, and Sit 9.6 +/-3.8 μmol/L. Lat was found to correlate with TC (r = 0.53), LDL-C (r = 0.36), and non-HDL-C (r = 0.35). No such correlations were observed for Sit (r = 0.162) or Cam (r = 0.153).

Conclusion: Our findings show that the high incidence of hypercholesterolemia during pregnancy is caused by increased endogenous cholesterol synthesis via lathosterol. The enormous rise of TC levels during pregnancy can be effectively used to detect familial hypercholesterolemia in women.

References

[1] Amundsen AL, Khoury J, Iversen P-O, et al. Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia. Atherosclerosis 2006; 189: 451-7.
https://doi.org/10.1016/j.atherosclerosis.2006.01.002
[2] Avis HJ, Hutten BA, Twickler MT, Kastelein JJP, et al. Pregnancy in women suffering from familial hypercholesterolemia: a harmful period for both mother and newborn? Curr Opinion Lipid 2009; 20: 484-490.
https://doi.org/10.1097/MOL.0b013e3283319127
[3] Desoye G, Schweditsch M, Pfeiffer K. Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and postpartum. J Clin Endocrin Metab 1987; 64: 704-12.
https://doi.org/10.1210/jcem-64-4-704
[4] Napoli C, Glass CK, WEitzum JL. et al. Influence of maternal hypercholesterolemia during pregnancy on progression of early atherosclerotic lesions in childhood. Fate of early lesions in children (FELIC) study. Lancet 1999; 354: 1234-41.
https://doi.org/10.1016/S0140-6736(99)02131-5
[5] Woollett LA. Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation. Am J Clin Nutr 2005; 82: 1155-1161. Schattauer. Fridrichsdorf, 2004.
[6] Bertrand N, Dahmane N. Sonic Hedgehog signalizing in forebrain development and its interactions with pathways that modify its effects. Trends Cell Biol 2006; 16: 597-605.
https://doi.org/10.1016/j.tcb.2006.09.007
[7] Chiang C. Cyclopia and defective axial pattering in mice lacking Sonic hedgehog gene function. Nature 1996; 383: 407-413.
https://doi.org/10.1038/383407a0
[8] Toleikyte I, Retterstol K, Leren TP, et al. Pregnancy outcomes in familial hypercholesterolemia. A register-based study. Circulation 2011; 124: 1606-14.
https://doi.org/10.1161/CIRCULATIONAHA.110.990929
[9] Anneda A, Mura S, Marcello C. HELP LDL-apheresis in two cases of familial hypercholesterolemic pregnant women. Transfusion Apheresis Sci 2011; 44: 21-24.
https://doi.org/10.1016/j.transci.2010.12.004
[10] Beigel Y, Bar J, Cohen Hod M. Pregnancy outcome in familial homozygous hypercholesterolemic females treated with long-term plasma exchange. Act Obst Gynecol Scand 1995; 77: 603-608.
https://doi.org/10.1034/j.1600-0412.1998.770605.x
[11] Bláha V, Bláha M, Lánská M, et al. LDL-afereza v lé?b? familiárních hyperlipoproteinemií [available only in Czech]. Vnit?ní lék 2014; 60: 970-975.
[12] Teunissen CE, Regente J, Bergman K, et al. Serum cholesterol precursors and metabolites and cognitive performance in an aging population. Neurobiol Aging 2003; 24: 147-55.
https://doi.org/10.1016/S0197-4580(02)00061-1
[13] Folch J, Lees M. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509.
[14] Thompson RH, Merola GV. A simplified alternative to the AOAC official method for cholesterol in multi-component food. AOAC Int 1993; 76: 1057-68.
[15] Hušek P, Chlormraven?any v analytické chemii jako ?inidla rychlé esterifikace Chloroformates in analytical chemistry as fast esterification agents . Unpublished PhD thesis. 1996. Available only in Czech in the archives of the Institute of Endocrinology, Prague, Czech Repulic.
[16] Hyánek J, Pehal, Dubská, et al. Lathosterol and nonchlesterol sterols in routine use for the differentiation and monitoring of dietary and drug induced treatment of hypercholesterolemias in children and adolescents. J Nutr Therap 2014; 3: 1-12.
https://doi.org/10.6000/1929-5634.2014.03.01.1
[17] deAssis SM, Seguro AC, Helou CMB. Effects of maternal hypercholesterolemia on pregnancy and development of offsprings. Pediatr Nephrol 2003; 18: 328-34.
[18] Khoury J, Henriksen T, Christophersen B, et al. Effect of a cholesterol-lowering diet on maternal cord, and neonatal lipids, and pregnancy outcome: A randomized clinical trial. Amer J Obstet Gynecol 2005; 193: 1292-301.
https://doi.org/10.1016/j.ajog.2005.05.016
[19] Mudd LM, Holzman CB, Catov JM, et al. Maternal lipids at mid-pregnancy and the risk of preterm delivery. Obstet Gynecol Scand 2012; 91: 726-735.
https://doi.org/10.1111/j.1600-0412.2012.01391.x
[20] Palinski W, Dármiento FP, Vitzum JL, et al. Maternal hypercholesterolemia and treatment during pregnancy influence the long-term progression of atherosclerosis in offspring of rabbits. Circ Res 2001; 89: 991-996.
https://doi.org/10.1161/hh2301.099646
[21] Catov JM, Bodnar LM, Kevin E, et al. Early pregnancy lipid concentrations and spontaneous preterm birth. Amer J Obstet Gynecol 2007; 197: 610e1-7.
[22] Edison RJ, Berg K, Remaley A, et al. Adverse birth outcome among mothers with low serum choleserol. Pediatrics 2007; 120: 723-733.
https://doi.org/10.1542/peds.2006-1939
[23] Hyánek J, Dubská L, Pejznochová H, et al. Hypercholesterolemie v t?hotenství – pathobiochemické a pathofyziologické zajímavosti pro vývoj aterosklerózy a její hodnocení v metabolické ambulanci [in Czech, English summary]. Klin Biochem Metab 2013; 21(42): 208-214.

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2018-01-05

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