Association Between Nonalcoholic Fatty Liver Disease and Cardiovascular Risk in Obese Children and Adolescents

doi:10.1016/j.cjca.2012.07.846

Canadian Journal of Cardiology

Volume 29, Issue 9, September 2013, Pages 1118-1125

https://doi.org/10.1016/j.cjca.2012.07.846 Get rights and content

Abstract

Background

The recent rise in the prevalence of obesity likely explains nonalcoholic fatty liver disease (NAFLD) epidemic worldwide. We evaluated cardiac functions, cardiovascular risk, and associated parameters with grades of NAFLD in obese children.

Methods

Four hundred obese children were enrolled in the study. Obese children with NAFLD were classified in 2 subgroups according to ultrasonographic visualizing. Ninety-three obese children with NAFLD (mean age 11.73 ± 2.72 years in group 2 and 12.69 ± 2.61 years in group 3) were compared with 307 age- and sex-matched non-NAFLD obese children and 150 control subjects. Laboratory parameters were measured during the fasting state. Pulsed and tissue Doppler echocardiography were performed. Intima-media (IMT) and epicardial adipose tissue (EAT) thicknesses were measured.

Results

NAFLD groups had a significantly higher body mass index (29.15 ± 3.42 and 30.46 ± 4.60; P < 0.001), total adipose tissue mass (37.95 ± 4.46% and 46.57 ± 6.45%; P < 0.001), higher insulin, alanine aminotransferase, and aspartate aminotransferase levels. Increased end-systolic thickness of the interventricular septum (P < 0.001), larger left ventricular mass (P < 0.003) and index (P < 0.003) were found in NAFLD groups. Children with NAFLD had higher Tei index values. Also, carotid artery IMT and EAT thickness were significantly higher in obese children. Waist and hip circumference, total cholesterol level, total adipose tissue mass, and interventricular septum were statistically different in NAFLD groups.

Conclusions

Children with NAFLD had mildly altered left and right ventricular functions and all obese children had increased IMT and EAT thickness. Also, grade of liver steatosis was positively correlated with total adipose tissue mass and interventricular septum systolic thickness.

Résumé

Introduction

La récente augmentation de la prévalence de l'obésité explique vraisemblablement l'épidémie mondiale de stéatose hépatique non alcoolique (SHNA). Nous avons évalué le fonctionnement cardiaque, le risque cardiovasculaire et les paramètres associés au degré de SHNA chez les enfants obèses.

Méthodes

Quatre cents (400) enfants obèses ont été inscrits à l'étude. Les enfants obèses ayant une SHNA ont été classifiés en 2 sous-groupes selon ce qui avait été visualisé à l'échographie. Quatre-vingt-treize (93) enfants obèses ayant une SHNA (âge moyen de 11,73 ± 2,72 ans dans le groupe 2 et de 12,69 ± 2,61 ans dans le groupe 3) ont été comparés à 307 enfants obèses sans SHNA appariés selon l'âge et le sexe et 150 témoins. Les paramètres de laboratoire ont été mesurés à jeun. Un écho-Doppler pulsé et tissulaire a été réalisé. L'épaisseur du tissu de l'intima-média (TIM) et du tissu adipeux épicardique (TAÉ) a été mesurée.

Résultats

Les groupes ayant une SHNA ont eu un indice de masse corporelle significativement plus élevé (29,15 ± 3,42 et 30,46 ± 4,60; P < 0,001), une masse tissulaire adipeuse totale (37,95 ± 4,46 % et 46,57 ± 6,45 %; P < 0,001), des concentrations plus élevées d'insuline, d'alanine aminotransférase et d'aspartate aminotransférase. L'augmentation de l'épaisseur du septum interventriculaire en fin de systole (P < 0,001), une masse (P < 0,003) et un indice (P < 0,003) de masse ventriculaire gauche plus grands ont été observés dans les groupes ayant une SHNA. Les enfants ayant une SHNA ont eu des valeurs plus élevées à l'indice de Tei. Aussi, l'épaisseur du TIM et du TAÉ de l'artère carotide a été significativement supérieure chez les enfants obèses. La circonférence à la taille et aux hanches, le taux de cholestérol total, la masse tissulaire adipeuse totale et le septum interventriculaire ont été statistiquement différents dans les groupes ayant une SHNA.

Conclusions

Les enfants ayant une SHNA ont eu une altération moyenne du fonctionnement des ventricules gauche et droit, et tous les enfants obèses ont eu une augmentation de l'épaisseur du TIM et du TAÉ. Aussi, le degré de la stéatose hépatique a corrélé positivement à la masse tissulaire adipeuse totale et à l'épaisseur systolique du septum interventriculaire.

Section snippets

Study population

Ninety-three obese children with NAFLD aged 6-17 years, 307 obese children without NAFLD, and 150 age- and sex-matched healthy control subjects, were included in the study. NAFLD was diagnosed with abdominal ultrasonography. Obese children who were already being followed by the Pediatric Endocrinology Outpatient Clinic were consecutively enrolled in this study. The control subjects were recruited from a population of nonobese healthy children and adolescents who were admitted to our hospital

Subject characteristics

Of 400 obese children, 93 (23.25%) were diagnosed as NAFLD (67 in group 2 and 26 in group 3). The demographic and laboratory characteristics of the study population are summarized in Table 1. Among all obese children type 2 diabetes was determined in 0.25% (n = 1) and impaired oral glucose tolerance test in 12% (n = 48). Also, the prevalence of hypertension in children with NAFLD was 15.87% (11 cases) for group 2 and 17.76% (5 cases) for group 3, and 15.76% (48 cases) in obese subjects without

Discussion

Several studies in adults and some in children have demonstrated that NAFLD is the primary hepatic complication of obesity and insulin resistance, and may be considered as the early hepatic manifestation of obesity and also metabolic syndrome.2, 4, 8 In this big cohort of study, we showed subclinically impaired cardiac functions in obese children with NAFLD. Also, we evaluated cardiovascular risk and associated parameters with grades of nonalcoholic liver steatosis in obese children with NAFLD.

Disclosures

The authors have no conflicts of interest to disclose.

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A more recent study suggested that NAFLD and advanced liver fibrosis, as estimated by fibrosis risk scores is common in patients with HFpEF, however, there is a limited independent association between liver fibrosis risk scores and clinical outcomes related to HF events.30 Numerous studies have reported early systolic and diastolic dysfunction in adults and/or children with NAFLD.27,31-34 Zhang et al. reported 36.3% prevalence of NAFLD defined by ultrasonography in 102 patients with HFrEF.1
Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD.
Non-alcoholic fatty liver disease in children and adolescents: Lifestyle change - A systematic review and meta-analysis
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Citation Excerpt :
The gold standard for the diagnosis of NAFLD is histology obtained using liver biopsy, which can determine the presence of steatosis, inflammation or fibrosis.2 The biopsy has some limitations; therefore, indirect methods have been used for diagnosis.7 –10
Introduction and aim. This manuscript seeks to analyze the impact of lifestyle changes on body mass index (BMI), aminotransferases and steatosis in children and adolescents with nonalcoholic fatty liver disease (NAFLD).
Material and methods. A review of PubMed, BIREME, Scopus, EMBASE, Medline and Web of Science databases 2015 was performed seeking studies addressing the impact of lifestyle interventions on children and/or adolescents with NAFLD. Inclusion were manuscripts written in Portuguese, English and Spanish, as well as age less than 18 years. Two reviewers performed the data extraction independently and differences were resolved by consensus. Outcome measures were BMI, serum aminotransferase levels and the presence of hepatic steatosis.
Results. The literature search identified 71,012 articles. After excluding 46,397 duplicates and other clearly irrelevant studies, 89 publications were reviewed in detail. Another 55 studies were excluded at this stage. Subsequently, 18 were excluded due to lack of data and three new articles were found in the review of the references of previously identified manuscripts. Therefore, 19 studies that had evaluated 923 subjects (477 boys and 446 girls) aged 6-18 years were included in the review. In most studies, the intervention included aerobic exercise and diet. In nine studies, BMI improved significantly following the intervention. The vast majority of studies reported a benefit from the intervention on aminotransferase levels. Lifestyle changes also had a significant impact on steatosis, reducing the risk by 61%.
Conclusion. In conclusion lifestyle changes lead to significant improvements in BMI, aminotransferase levels and hepatic steatosis in children and adolescents with NAFLD.
Comparison of the Phenotype and Approach to Pediatric vs Adult Patients with Nonalcoholic Fatty Liver Disease
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However, some data are controversial. Manco et al92 reported no association between intima-media thickness and liver histology in obese children and adolescents with NAFLD and more recent studies based on surrogate biomarkers of NAFLD or liver biopsy found an increased interventricular septum thickness at end diastole and at end systole.93,94 However, both adult and pediatric studies have shown that NAFLD has been associated with impaired left ventricular function and adverse changes in cardiac geometry, which are well-established risk factors for cardiovascular events.95,96
Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic noncommunicable diseases in Westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities, such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults, and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over the patient’s lifetime. We review the similarities and differences of NAFLD between children and adults.
Quantification of liver fat: A comprehensive review
2016, Computers in Biology and Medicine
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Microsteatosis is usually more severe than simple steatosis and associated with toxin-induced injury, acute viral and metabolic abnormalities [4]. Macrosteatosis is generally associated with diabetes, dyslipidemia, obesity, alcohol abuse and hyperlipidemia since it affects determination of insulin resistance (i.e.,interfering insulin signaling) and also increases risk of cardiac complications and cardiovascular disease mortality [8–18]. The majority of fatty livers are related to NAFLD (Section 1.1).
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Cardiovascular disease is the primary cause of death in obese and diabetic patients. In these groups of patients, the alterations of epicardial adipose tissue (EAT) contribute to both vascular and myocardial dysfunction. Therefore, it is of clinical interest to determine the mechanisms by which EAT influences cardiovascular disease. Two key factors contribute to the tight intercommunication among EAT, coronary arteries and myocardium. One is the close anatomical proximity between these tissues. The other is the capacity of EAT to secrete cytokines and other molecules with paracrine and vasocrine effects on the cardiovascular system. Epidemiological studies have demonstrated that EAT thickness is associated with not only metabolic syndrome but also atherosclerosis and heart failure. The evaluation of EAT using imaging modalities, although effective, presents several disadvantages including radiation exposure, limited availability and elevated costs. Therefore, there is a clinical interest in EAT as a source of new biomarkers of cardiovascular and endocrine alterations. In this review, we revise the mechanisms involved in the protective and pathological role of EAT and present the molecules released by EAT with greater potential to become biomarkers of cardiometabolic alterations.
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Clinical researchAssociation Between Nonalcoholic Fatty Liver Disease and Cardiovascular Risk in Obese Children and Adolescents

Abstract

Background

Methods

Results

Conclusions

Résumé

Introduction

Méthodes

Résultats

Conclusions

Section snippets

Study population

Subject characteristics

Discussion

Disclosures

Gastroenterology

Pediatr Neonatol

Atherosclerosis

Atherosclerosis

J Am Soc Echocardiogr

Trends Endocrinol Metab

Nutr Metab Cardiovasc Dis

Nutr Metab Cardiovasc Dis

Nutr Metab Cardiovasc Dis

J Am Soc Echocardiogr

Impairment of the left ventricular systolic and diastolic function in patients with non-alcoholic fatty liver disease

Cardiol J

Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

World J Gastroenterol

Non-alcoholic fatty liver disease: an early mediator predicting metabolic syndrome in obese children?

World J Gastroenterol

Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment

J Clin Gastroenterol

Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease

J Clin Endocrinol Metab

NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study

Am J Gastroenterol

Clinical research
Association Between Nonalcoholic Fatty Liver Disease and Cardiovascular Risk in Obese Children and Adolescents