title: Altered Cholesterol Metabolism and Hypocholesterolemia in Patients with Single Ventricle following Fontan Palliation.
abstract: OBJECTIVE
  To assess whether an abnormality in cholesterol absorption or synthesis may be associated with hypocholesterolemia in patients with single ventricle anatomy following Fontan palliation.
  
  
  METHODS
  This is a cross-sectional study of 21 patients with hypocholesterolemia following Fontan procedure and age/sex-matched healthy controls, with median age of 13.4 (IQR 10.6-16.1) years. Laboratory values of several biomarkers, including phytosterols and 5-α-cholestanol (for cholesterol absorption) and lathosterol (for cholesterol biosynthesis), as well as cholesterol levels, inflammatory markers, and indices of liver function were compared between patients following Fontan procedure and controls.
  
  
  RESULTS
  The Fontan cohort had significantly lower total cholesterol (mean 117 ± SD 13.9, vs 128 ± 19.2 mg/dL, P = .03) and free cholesterol (35.5 ± 4.5 vs 39.2 ± 5.4 mg/dL, P = .02) compared with control patients. There was an increase in normalized 5-α-cholestanol (1.51 ± 0.6 vs 1.14 ± 0.37 μg/mL, P = .02), and a significantly lower lathosterol/5-α-cholestanol ratio (0.70 ± 0.38 vs 1.11 ± 0.76, P = .04). There was a strong correlation (r = 0.78, P < .0001) between lathosterol and cholesterol levels in the Fontan cohort, not seen in controls (r = 0.47, P = .04). The Fontan cohort also had significantly higher C-reactive protein, transaminases, total bilirubin, and gamma-glutamyl transferase levels.
  
  
  CONCLUSIONS
  Patients with hypocholesterolemia following Fontan procedure have evidence of increased cholesterol absorption and decreased cholesterol synthesis. As cholesterol absorption efficiency is a regulated process, this finding suggests an upregulation of cholesterol absorption as a result of decreased cholesterol production. In the setting of elevated liver indices and possible inflammation, this finding supports a growing body of data suggesting development of liver disease in patients receiving Fontan.
authors.affiliation: The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: wendy.whiteside@cchmc.org.
authors.forename: Wendy
authors.initials: W
authors.lastname: Whiteside
authors.affiliation: Division of Metabolism Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: Meng
authors.initials: M
authors.lastname: Tan
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University, St. Louis, MO.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Ostlund
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, MI.
authors.forename: Sunkyung
authors.initials: S
authors.lastname: Yu
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University, St. Louis, MO.
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, MI.
authors.forename: Albert
authors.initials: A
authors.lastname: Rocchini
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D004083:Cholestanol / Q000097:blood; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D018729:Fontan Procedure / Q000379:methods*; D006801:Humans; D007009:Hypolipoproteinemias / Q000628:therapy*; D007249:Inflammation; D008099:Liver / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D010840:Phytosterols / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D010840:Phytosterols; C001521:lathosterol; D004083:Cholestanol; D002097:C-Reactive Protein; D002784:Cholesterol