TY - JOUR
T1 - Fontan-associated dyslipidemia
AU - Lubert, Adam M.
AU - Alsaied, Tarek
AU - Palermo, Joseph J.
AU - Anwar, Nadeem
AU - Urbina, Elaine M.
AU - Brown, Nicole M.
AU - Alexander, Craig
AU - Almeneisi, Hassan
AU - Wu, Fred
AU - Leventhal, Andrew R.
AU - Aldweib, Nael
AU - Mendelson, Michael
AU - Opotowsky, Alexander R.
N1 - Publisher Copyright:
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2021
Y1 - 2021
N2 - BACKGROUND: Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocho-lesterolemia 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 func-tional 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.
AB - BACKGROUND: Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocho-lesterolemia 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 func-tional 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.
KW - Adult congenital heart disease
KW - Fontan
KW - High-density lipoprotein cholesterol
KW - Lipids
KW - Single ventricle
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U2 - 10.1161/JAHA.120.019578
DO - 10.1161/JAHA.120.019578
M3 - Article
C2 - 33787283
AN - SCOPUS:85104047554
SN - 2047-9980
VL - 10
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 7
M1 - e019578
ER -