Alanine Aminotransferase and High Sensitivity C-Reactive Protein: Correlates of Cardiovascular Risk Factors in Youth ANTÔNIO C. OLIVEIRA, MD, ANA M. OLIVEIRA, MD, MARCELE S. ALMEIDA, RN, AGNALUCE M. SILVA,PHD, LUIS ADAN,PHD, AND ANA M. LADEIA, MD, PHD 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). Measure- ments 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. (J Pediatr 2008;152:337-42) O besity is on the rise in youth 1,2 and is a predictor of adulthood obesity. 3,4 Abdominal obesity is an independent and modifiable risk factor for cardiovas- cular disease (CVD) and type 2 diabetes mellitus (DM2). 5 The adipose tissue may play a role in the development of a chronic low-grade inflammatory state that may lead to endothelial dysfunction and vascular damage. 7 Some studies have shown a relationship between high sensitivity C-reactive protein (hs-CRP) and CVD, 8,9 as well as DM. 10 Recent evidence suggests that elevated liver enzymes, especially alanine aminotrans- ferase (ALT) may serve as a surrogate marker for DM2. 11 The Insulin Resistance Atherosclerosis Study demonstrated that individuals with the highest levels of ALT had significantly greater risk of developing diabetes, irrespective of CRP 10 levels, and there- fore, when used in combination, these two markers may have additive predictive ability for identifying subjects at risk of developing DM. 10 We hypothesized that clinical and metabolic risk factors for cardiovascular disease, such as obesity, abdominal obesity, dyslipidemia, glucose metabolism disturbances, insulin resistance (IR), and metabolic syndrome are associated with increased ALT and hs-CRP. Thus, the association between hs-CRP and ALT with clinical and metabolic measures was evaluated in a sample of overweight Brazilian children and adolescents. ALT Alanine aminotransferase BMI Body mass index CVD Cardiovascular disease DBP Diastolic blood pressure HOMA Homeostatic model assessment hs-CRP High-sensitivity C-reactive protein IR Insulin resistance MS Metabolic syndrome SBP Systolic blood pressure TG Triglycerides From the Bahian School of Medicine and Public Health (A.C.O., A.M.L.), Science De- velopment Foundation of Bahia, Bahia, Bra- zil; Department of Health (A.C.O., A.M.O., M.S.A.), State University of Feira de San- tana, Feira de Santana, Bahia, Brazil; Depart- ment of Pediatrics (A.M.O., L.A.), Federal University of Bahia School of Medicine, Sal- vador, Bahia, Brazil; and Department of Clinical Pathology Laboratory (A.M.S.), Sal- vador, Bahia, Brazil. 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. Submitted for publication Mar 19, 2007; last revision received May 29, 2007; ac- cepted Jul 6, 2007. Reprint requests: Dr. Antonio C. Oliveira, Av. Senhor dos Passos, 407, Feira de San- tana-BA - Brazil 44010-230. E-mail: leegoza@ uol.com.br. 0022-3476/$ - see front matter Copyright © 2008 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2007.07.013 337