Department of Pediatrics Cincinnati Children's Hospital Heart InstituteUniversity of Cincinnati College of Medicine Cincinnati OH.
Department of Pediatrics Division of Gastroenterology Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati College of Medicine Cincinnati OH.
J Am Heart Assoc. 2021 Apr 6;10(7):e019578. doi: 10.1161/JAHA.120.019578. Epub 2021 Mar 31.
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, <0.0001), low-density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, <0.0001), and high-density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, <0.0001) than controls. In those with a Fontan, high-density lipoprotein cholesterol was inversely correlated with body mass index (=-0.30, <0.0001), high-sensitivity C-reactive protein (=-0.27, =0.0006), and alanine aminotransferase (=-0.18, =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 [=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 [=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.
低胆固醇血症是肝脏疾病的标志物，接受 Fontan 循环的患者可能因 Fontan 相关肝病或炎症而出现低胆固醇血症。我们研究了 Fontan 循环成人的循环脂质，并评估了其与临床特征和不良事件的相关性。
我们招募了 164 名年龄≥18 岁的 Boston 成人先天性心脏病生物库的 Fontan 循环门诊患者，并将其与 81 名健康对照者进行了比较。结局是无选择性心血管住院或死亡的联合结局。Fontan 组（中位年龄 30.3[四分位间距 22.8-34.3 岁]，42%为女性）的总胆固醇（149.0±30.1mg/dL 比 190.8±41.4mg/dL，<0.0001）、低密度脂蛋白胆固醇（82.5±25.4mg/dL 比 102.0±34.7mg/dL，<0.0001）和高密度脂蛋白胆固醇（42.8±12.2mg/dL 比 64.1±16.9mg/dL，<0.0001）均低于对照组。在 Fontan 组中，高密度脂蛋白胆固醇与体重指数（=-0.30，<0.0001）、高敏 C 反应蛋白（=-0.27，=0.0006）和丙氨酸氨基转移酶（=-0.18，=0.02）呈负相关，但与其他肝病标志物无关。在调整年龄、性别、体重指数和功能分级后，较低的高密度脂蛋白胆固醇与联合结局的风险增加独立相关（每降低 10mg/dL 的风险比[HR]，1.37；95%CI，1.04-1.81[=0.03]）。当将 log 高敏 C 反应蛋白添加到模型中时，这种关系减弱（HR，1.26；95%CI，0.95-1.67[=0.10]）。总胆固醇、低密度脂蛋白胆固醇和三酰甘油与联合结局无关。
Fontan 循环与胆固醇水平降低有关，而较低的高密度脂蛋白胆固醇与不良结局有关。这种关联可能是由炎症引起的。需要进一步研究来了解 Fontan 相关肝病的严重程度与脂质代谢之间的关系。
