Affiliation:
1. Department of Pediatrics Cincinnati Children's Hospital Heart InstituteUniversity of Cincinnati College of Medicine Cincinnati OH
2. Department of Pediatrics Division of Gastroenterology Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati College of Medicine Cincinnati OH
3. Department of Medicine Digestive Disease Division University of Cincinnati College of Medicine Cincinnati OH
4. Department of Cardiology Boston Children's HospitalHarvard Medical School Boston MA
5. Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA
6. Gill Heart Institute University of Kentucky Lexington KY
Abstract
Background
Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan‐associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events.
Methods and Results
We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8–34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL,
P
<0.0001), low‐density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL,
P
<0.0001), and high‐density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL,
P
<0.0001) than controls. In those with a Fontan, high‐density lipoprotein cholesterol was inversely correlated with body mass index (
r
=−0.30,
P
<0.0001), high‐sensitivity C‐reactive protein (
r
=−0.27,
P
=0.0006), and alanine aminotransferase (
r
=−0.18,
P
=0.02) but not with other liver disease markers. Lower high‐density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04–1.81 [
P
=0.03]). This relationship was attenuated when log high‐sensitivity C‐reactive protein was added to the model (HR, 1.26; 95% CI, 0.95–1.67 [
P
=0.10]). Total cholesterol, low‐density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome.
Conclusions
The Fontan circulation is associated with decreased cholesterol levels, and lower high‐density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan‐associated liver disease and lipid metabolism.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
8 articles.
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