Wendy Whiteside1, Meng Tan2, Richard E Ostlund3, Sunkyung Yu4, Lina Ma3, Albert Rocchini4. 1. The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: wendy.whiteside@cchmc.org. 2. Division of Metabolism Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. 3. Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University, St. Louis, MO. 4. Division of Pediatric Cardiology, Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, MI.
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. STUDY DESIGN: 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.
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. STUDY DESIGN: 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: Yongmei Liu; Josef Coresh; Joseph A Eustace; J Craig Longenecker; Bernard Jaar; Nancy E Fink; Russell P Tracy; Neil R Powe; Michael J Klag Journal: JAMA Date: 2004-01-28 Impact factor: 56.272
Authors: Jack Rychik; Gruschen Veldtman; Elizabeth Rand; Pierre Russo; Jonathan J Rome; Karen Krok; David J Goldberg; Anne Marie Cahill; Rebecca G Wells Journal: Pediatr Cardiol Date: 2012-04-26 Impact factor: 1.655
Authors: Miriam Michel; Karl-Otto Dubowy; Manuela Zlamy; Daniela Karall; Mark Gordian Adam; Andreas Entenmann; Markus Andreas Keller; Jakob Koch; Irena Odri Komazec; Ralf Geiger; Christina Salvador; Christian Niederwanger; Udo Müller; Sabine Scholl-Bürgi; Kai Thorsten Laser Journal: Ther Adv Chronic Dis Date: 2020-04-27 Impact factor: 5.091
Authors: Adam M Lubert; Tarek Alsaied; Joseph J Palermo; Nadeem Anwar; Elaine M Urbina; Nicole M Brown; Craig Alexander; Hassan Almeneisi; Fred Wu; Andrew R Leventhal; Nael Aldweib; Michael Mendelson; Alexander R Opotowsky Journal: J Am Heart Assoc Date: 2021-03-31 Impact factor: 5.501
Authors: Nicholas Felici; Da Liu; Josh Maret; Mariana Restrepo; Yuliya Borovskiy; Jihane Hajj; Wesley Chung; Krzysztof Laudanski Journal: Front Cardiovasc Med Date: 2021-11-15
Authors: Evi Ritmeester; Veerle A Veger; Jelle P G van der Ven; Gabrielle M J W van Tussenbroek; Carine I van Capelle; Floris E A Udink Ten Cate; Willem A Helbing Journal: Front Cardiovasc Med Date: 2022-03-22