Alanine Aminotransferase and High Sensitivity C-Reactive Protein: Correlates of Cardiovascular Risk Factors in Youth

doi:10.1016/j.jpeds.2007.07.013

The Journal of Pediatrics

Volume 152, Issue 3, March 2008, Pages 337-342

https://doi.org/10.1016/j.jpeds.2007.07.013 Get rights and content

Objective

The association between high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) with clinical/metabolic variables was evaluated in overweight Brazilian children and adolescents.

Study design

Oral glucose tolerance test was performed in 407 students (273 overweight/obese, 11.3 ± 3.1 y). Measurements included body mass index (BMI), waist circumference (WC), blood pressure, lipids, insulin, hs-CRP, and ALT. Overweight/obese was defined using BMI z-score; insulin resistance (IR) by homeostatic model assessment: insulin resistance (HOMA-IR); and metabolic syndrome (MS) in accordance with the modified NCEP-ATPIII.

Results

As weight increased, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), insulin, HOMA-IR, hs-CRP, ALT, ALT, hs-CRP, and AST and the number of MS components (nMSc) also increased (P ≤ .001 for all). Subjects with hs-CRP and ALT above the median had higher BMI z-score, WC, SBP, DBP, TG, AST, insulin, HOMA-IR, and nMSc than those with both markers below the median (P ≤ .002 for all). After adjustment for age, sex and ethnicity, BMI z-score (OR, 1.5; CI, 1.38 to 1.86; P < .001), WC (OR,1.3; CI, 1.19 to 1.43; P < .001) SBP (OR, 1.2; CI, 1.03 to 1.38; P = .015), DBP (OR, 1.4; CI, 1.15 to 1.69; P < .001), TG (OR, 1.8; CI, 1.29 to 2.62; P < .001), insulin (OR, 1.4; CI, 1.23 to 1.71; P < .001), HOMA-IR (OR, 1.2; CI, 1.09 to 1.29; P < .001) and nMSc (OR, 2; CI, 1.16 to 3.47; P = .012) were independently associated with high ALT and hs-CRP. For every 5-cm increase in WC and every 1-point increase in BMI z-score, there were a 1.3- and 1.5-fold greater chance of having increased ALT and hs-CRP, respectively.

Conclusions

Simultaneous measurements of ALT and hs-CRP should be considered as a screening test for metabolic syndrome and cardiovascular disease risk factors in overweight/obese children/adolescents.

Section snippets

Study Participants and Procedures

The study was conducted in Feira de Santana, Bahia, Brazil, at state and private schools. Selection was based on lists provided by the schools in the proportion of 2 overweight or obese to 1 normal weight subject. 407 students (229 girls; 273 with excessive weight; mean age ± SD, 11.3 ± 3.1 years) were included in the protocol. Subjects were eligible if they were healthy, 4 to 18 years of age, had no history of current or past excessive alcohol drinking, as defined by and average daily

Results

Seventy-two subjects (17.7%) fulfilled the MS diagnosis and their hs-CRP and ALT means were 3.4 ± 2.9 mg/L and 29.2 ± 15.6 U/L, respectively. Anthropometric and metabolic data are shown in Table I. Values for BMI z-score (P < .001), WC (P < .001), SBP (P < .001), DBP (P < .001), TG (P < .001), insulin (P < .001), and HOMA-IR (P < .001) increased significantly with increasing weight and HDL-C (P < .001) decreased. There were no differences between age (P = .072), sex, (P = .067), and fasting

Discussion

Chronic conditions, such as CVD, are now affecting young people and generally require ongoing treatment for many years. In developing countries, these diseases alone account for nearly 27% of all deaths, and 9% of all years of healthy life lost to disease worldwide.²⁰ Despite this, there are some limitations of current risk strategies to predict CVD.²¹

CVD is increasing in young people and it has been confirmed that children with high systolic blood pressure are at increased risk of hypertension

References (30)

R. Retnakaran et al.
Nontraditional cardiovascular risk factors in pediatric metabolic syndrome
J Pediatr
(2006)
J.R. Fernandez et al.
Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents
J Pediatr
(2004)
A.M. Gotto
Role of C-reactive protein in coronary risk reduction: focus on primary prevention
Am J Cardiol
(2007)
T.A. Coutinho et al.
Associations of serum uric acid with markers of inflammation, metabolic syndrome, and subclinical coronary atherosclerosis
Am J Hypertens
(2007)
N.C. Bhalodkar et al.
Accuracy of the ratio of triglycerides to high-density lipoprotein cholesterol for predicting low-density lipoprotein cholesterol particle sizes, phenotype B, and particle concentrations among Asian Indians
Am J Cardiol
(2006)
M.R. Riley et al.
Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists
J Pediatr
(2005)
P. Hossain et al.
Obesity and diabetes in the developing world: a growing challenge
N Engl J Med
(2007)
R. Weiss et al.
Obesity and the metabolic syndrome in children and adolescents
N Engl J Med
(2004)
D.S. Freedman et al.
Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study
J Pediatr
(2007)
E.E. Calle et al.
Body-mass index and mortality in a prospective cohort of US adults
N Engl J Med
(1999)

S.M. Haffner

Relationship of metabolic risk factors and development of cardiovascular disease and diabetes

Obesity

(2006)

A.H. Mokdad et al.

The continuing epidemics of obesity and diabetes in the United States

JAMA

(2001)

A. Festa et al.

Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS)

Circulation

(2002)

S.M. Haffner

The Metabolic Syndrome: inflammation, diabetes mellitus, and cardiovascular disease

Am J Cardiol

(2006)

A.J. Hanley et al.

Liver markers and development of the metabolic syndrome: the Insulin resistance Atherosclerosis Study

Diabetes

(2004)

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White blood cell count may identify abnormal cardiometabolic phenotype and preclinical organ damage in overweight/obese children
2016, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
In particular, high WBCc is associated with altered glucose metabolism as well as an increased risk of subclinical signs of cardiac, vascular and liver damage. Previous studies have analyzed the association between pediatric obesity and low-grade chronic inflammation mainly using serological markers such as high-sensitivity C-reactive protein (hs-CRP) and cytokines [22,23]. However, these indices are not practical in the clinical setting because they are not usually available in routine biochemical studies particularly in pediatric subjects.
Subclinical inflammation is a central component of cardiometabolic disease risk in obese subjects. The aim of the study was to evaluate whether the white blood cell count (WBCc) may help to identify an abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children.
A cross-sectional sample of 2835 Ow/Ob children and adolescents (age 6–18 years) was recruited from 10 Italian centers for the care of obesity. Anthropometric and biochemical variables were assessed in the overall sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315 children, respectively. Insulin resistance and whole body insulin sensitivity index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and Matsuda's test. Groups divided in quartiles of WBCc significantly differed for body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and relative wall thickness. Children with high WBCc (≥8700 cell/mm³) showed a 1.3–2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT, or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender, pubertal status, BMI and centers.
This study shows that WBCc is associated with early derangements of glucose metabolism and preclinical signs of liver, vascular and cardiac damage. The WBCc may be an effective and low-cost tool for identifying Ow and Ob children at the greatest risk of potential complications.
Association of ALT and the metabolic syndrome among Mexican children
2014, Obesity Research and Clinical Practice
Citation Excerpt :
ALT levels have been used as surrogate measures of NAFLD; it has been found reliable as a screening tool for fatty liver [6,8,9,15–20], and has the closest association with liver fat accumulation [21]. ALT significantly predicts incident type 2 diabetes [17,22,23], coronary heart disease [21] and independently predicts the incidence of MetS components [17,24,25]. NAFLD prevalence determined by ALT elevation in obese children has been reported from 9.5% to 25.5% [6,16,20,26–28], and frequency seems to be higher in those children with hyperlipidemia and type 2 diabetes [7,29].
Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6–12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0–8.0) to 22.4% for the obese one (95%CI 16.2–30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1–65.9) and 24.1% in the normal ALT one (95%CI 18.1–31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children.
Determination of serum alkaline phosphatase reference in healthy children aged 1-18 years
2022, Caspian Journal of Internal Medicine
Nutritional status, diet quality and inflammatory markers in adolescents
2021, Archivos Latinoamericanos de Nutricion
Association of Alanine Aminotransferase With Different Metabolic Phenotypes of Obesity in Children and Adolescents: The CASPIAN-V Study
2020, Frontiers in Endocrinology
Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: Relation to transient elastography with controlled attenuation parameter
2020, European Journal of Gastroenterology and Hepatology

View all citing articles on Scopus

: Supported by the Research Foundation of Bahia (FAPESB), Bahia, Brazil.

: This article is part of Antonio C. Oliveira’s MSc Thesis of Bahian School of Medicine and Public Health Postgraduate Course.

View full text

Original articleAlanine Aminotransferase and High Sensitivity C-Reactive Protein: Correlates of Cardiovascular Risk Factors in Youth

Objective

Study design

Results

Conclusions

Section snippets

Study Participants and Procedures

Results

Discussion

J Pediatr

J Pediatr

Am J Cardiol

Am J Hypertens

Am J Cardiol

J Pediatr

Obesity and diabetes in the developing world: a growing challenge

N Engl J Med

Obesity and the metabolic syndrome in children and adolescents

N Engl J Med

Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study

J Pediatr

Body-mass index and mortality in a prospective cohort of US adults

N Engl J Med

Relationship of metabolic risk factors and development of cardiovascular disease and diabetes

Obesity

The continuing epidemics of obesity and diabetes in the United States

JAMA

Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS)

Circulation

The Metabolic Syndrome: inflammation, diabetes mellitus, and cardiovascular disease

Am J Cardiol

Liver markers and development of the metabolic syndrome: the Insulin resistance Atherosclerosis Study

Diabetes

Original article
Alanine Aminotransferase and High Sensitivity C-Reactive Protein: Correlates of Cardiovascular Risk Factors in Youth