Functional and morphological vascular changes in pediatric nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has been consistently found to be associated with features of the metabolic syndrome (MS), a condition carrying a high risk of cardiovascular events. The present study aimed to determine whether, in children and adolescents, NAFLD is atherogenic beyond its association with MS and its components. We assessed both flow‐mediated dilation of the brachial artery (FMD) and carotid intima‐media thickness (cIMT), along with lipid profile, glucose, insulin, insulin resistance, and high‐sensitivity C‐reactive protein (CRPHS), in 250 obese children, 100 with and 150 without NAFLD, and 150 healthy normal‐weight children. NAFLD was diagnosed by ultrasound examination and persistently elevated alanine aminotransferase, after exclusion of infectious and metabolic disorders. Compared to controls and children without liver involvement, those with ultrasound‐diagnosed NAFLD (and elevated alanine aminotransferase) demonstrated significantly impaired FMD and increased cIMT. Patients with NAFLD had more features of MS and elevated CRPHS levels. In addition, percent FMD was remarkably reduced, whereas cIMT was increased in obese children with MS compared to those without MS. Using logistic regression analysis, the presence of NAFLD was found to be an independent predictor of low percent FMD (odds ratio, 2.25 [95% confidence interval, 1.29 to 3.92]; P = 0.004) as well as of increased cIMT (1.98 [1.16 to 3.36]; P = 0.031), after adjustment for age, gender, Tanner stage, and presence of MS. When we analyzed the relations between cIMT and measures of FMD in patients with NAFLD, the disease was associated with increased cIMT in children with impaired FMD status. Conclusion: The presence of liver disease entails more severe functional and anatomic changes in the arterial wall. Its detection may help identify individuals with increased cardiometabolic risk. (HEPATOLOGY 2010.)

[1]  S. Grundy Metabolic syndrome scientific statement by the American Heart Association and the National Heart, Lung, and Blood Institute. , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[2]  G. Grugni,et al.  Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test , 2000, International Journal of Obesity.

[3]  F. Ippoliti,et al.  Increased T-helper interferon-γ-secreting cells in obese children , 2006 .

[4]  G. Targher,et al.  Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. , 2007, Atherosclerosis.

[5]  A. Koçyiğit,et al.  Intima-Media Thickness of Carotid Artery and Susceptibility to Atherosclerosis in Obese Children With Nonalcoholic Fatty Liver Disease , 2008, Journal of pediatric gastroenterology and nutrition.

[6]  L. N. Valenti,et al.  Carotid artery intima-media thickness in nonalcoholic fatty liver disease. , 2008, The American journal of medicine.

[7]  Terho Lehtimäki,et al.  Conventional Cardiovascular Risk Factors and Metabolic Syndrome in Predicting Carotid Intima-Media Thickness Progression in Young Adults: The Cardiovascular Risk in Young Finns Study , 2009, Circulation.

[8]  V. Cantisani,et al.  Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children , 2008, Pediatric Research.

[9]  J. Schwimmer,et al.  Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease , 2008, Circulation.

[10]  T. Laitinen,et al.  Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. , 2003, JAMA.

[11]  T. Reinehr,et al.  Relationship between metabolic syndrome definitions for children and adolescents and intima-media thickness. , 2008, Atherosclerosis.

[12]  A. Folsom,et al.  The continuum of risk: vascular pathophysiology, function, and structure. , 2004, Circulation.

[13]  T. Laitinen,et al.  Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study. , 2008, European heart journal.

[14]  S. Daniels,et al.  Instability in the Diagnosis of Metabolic Syndrome in Adolescents , 2007, Circulation.

[15]  A. Feldstein,et al.  Severity of Liver Injury and Atherogenic Lipid Profile in Children With Nonalcoholic Fatty Liver Disease , 2010, Pediatric Research.

[16]  A. Yeung,et al.  Close relation of endothelial function in the human coronary and peripheral circulations. , 1995, Journal of the American College of Cardiology.

[17]  E. Benjamin,et al.  Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. , 2002, Journal of the American College of Cardiology.

[18]  M. Uribe,et al.  Current concepts in the pathogenesis of nonalcoholic fatty liver disease , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[19]  D. Celermajer,et al.  Endothelial dysfunction: does it matter? Is it reversible? , 1997, Journal of the American College of Cardiology.

[20]  P. Rosenthal,et al.  Association Between Metabolic Syndrome and Liver Histology Among Children With Nonalcoholic Fatty Liver Disease , 2010, The American Journal of Gastroenterology.

[21]  A. Kotronen,et al.  Fatty Liver: A Novel Component of the Metabolic Syndrome , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[22]  B. Netterstrøm,et al.  The intima media thickness and coronary risk factors. , 2001, International angiology : a journal of the International Union of Angiology.

[23]  Beverley Balkau,et al.  Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population , 2009, Hepatology.

[24]  S. Daniels,et al.  Youth With Obesity and Obesity-Related Type 2 Diabetes Mellitus Demonstrate Abnormalities in Carotid Structure and Function , 2009, Circulation.

[25]  Emilio Ros,et al.  Nonalcoholic Fatty Liver Disease Is Associated With Carotid Atherosclerosis: A Case–Control Study , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[26]  M. Bond,et al.  Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study. , 2004, Journal of the American College of Cardiology.

[27]  A. Lonardo,et al.  Apolipoprotein synthesis in nonalcoholic steatohepatitis , 2002, Hepatology.

[28]  G. Marchesini,et al.  Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease , 2005, Hepatology.

[29]  D. Kim,et al.  Association between nonalcoholic fatty liver disease and carotid intima-media thickness according to the presence of metabolic syndrome. , 2009, Atherosclerosis.

[30]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[31]  G. Bedogni,et al.  Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease. , 2010, Atherosclerosis.

[32]  G. Svegliati-Baroni,et al.  From the metabolic syndrome to NAFLD or vice versa? , 2010, Digestive and Liver Disease.