Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents
Introduction
Over the last few decades obesity has reached epidemic proportions in children as well as adults in developed countries and more recently in developing countries. Obesity is associated with increased risk of insulin resistance, dyslipidemia, elevated blood pressure (BP), and inflammation, which is linked to an increased risk of type 2 diabetes and cardiovascular disease (CVD), among other diseases [1]. Thus, there is growing interest in the identification of cardiovascular risk factors at an early stage of life because they might have long-term effects on arterial health.
In adults, lipoprotein ratios have been recognized as being more useful than isolated lipid values for cardiovascular risk assessment because they better reflect the interactions between lipid fractions [2]. In particular, the triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, namely small low-density lipoprotein cholesterol (LDL-C) and small HDL-C, as well as of insulin resistance, metabolic syndrome (MetS), and high cardiovascular risk [3], [4]. In childhood, the clinical and prognostic value of lipid ratios has been much less investigated [5], [6], [7], [8], [9]. Quijada et al. showed that the TG/HDL-C ratio was useful in identifying prepubertal children at risk for obesity, dyslipidemia, hypertension, and MetS [5]. In a large sample of high school adolescents, Musso et al. demonstrated that the TG/HDL-C ratio and high-sensitivity C-reactive protein (hsCRP) positively correlated with body mass index (BMI) and waist circumference (WC) [6]. Recently, Weiss et al. have demonstrated that the TG/HDL-C ratio measured in late adolescence predicts a proatherogenic lipid profile in adulthood independently of obesity and weight gain [7]. Giannini et al. demonstrated that the TG/HDL-C ratio is associated with insulin resistance particularly in white girls and boys but not significantly in African Americans or Hispanics [8]. Thus the TG/HDL-C ratio may vary by ethnicity. Interestingly, Di Bonito et al. have shown that a TG/HDL-C ratio ≥2.0 is associated with several cardiometabolic risk factors and proves to be useful in identifying children with a high risk of elevated ALT and left ventricular hypertrophy [9]. However, correlations of the TG/HDL-C ratio with early vascular damage in children and adolescents are very limited [10], [11].
Atherosclerosis begins in childhood. Pre-clinical vascular changes can be assessed noninvasively and reliably by ultrasound in young subjects. Increased carotid artery intima-media thickness (cIMT) reflects early structural abnormalities during atherogenesis. It correlates with cardiovascular risk factors and the severity of coronary atherosclerosis, and predicts cardiovascular events [12], [13]. Exposure to atherogenic lipid profile in early life might induce changes in arteries that contribute to the development of atherosclerosis. Therefore, the aim of the present study was to explore in children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes as well as with cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD).
Section snippets
Study population
A total of 391 Caucasian overweight/obese children and adolescents (282 boys) with a median age of 10.10 (range of 6–16) years were included in the study. Among them, 118 (30.2%) were overweight, and 273 (69.8%) were obese. They were consecutively enrolled at the outpatient clinics of the Department of Pediatrics, Sapienza University of Rome, Italy. Exclusion criteria were the presence of renal disease; type 1 or 2 diabetes; any condition known to influence body composition, insulin action, or
Baseline characteristics of the entire study population according to tertiles of TG/HDL-C
Baseline characteristics of all participants according to tertiles of TG/HDL-C ratio are summarized in Table 1. There was a progressive increase in BMI, BMI-SDS, WC, systolic and diastolic BP, liver enzymes, glucose, insulin, HOMA-IR, and hsCRP, and a progressive decrease in HDL-C from the lower to the upper tertile of the TG/HDL-C ratio. A statistically significant difference across tertiles was also found in maximum cIMT (P = 0.009) and mean cIMT (P = 0.004) (Table 1). In contrast, no
Discussion
In this study we show that a high TG/HDL-C ratio is associated with an unfavorable cardiovascular and metabolic profile. In particular, this is the first report showing, in a large sample of Caucasian children, that a high TG/HDL-C ratio is significantly associated with an increased cIMT. This association remains significant after adjustment for total and visceral adiposity, systemic inflammation, high blood pressure, insulin resistance, and NAFLD. Our data suggest that using the TG/HDL-C ratio
Acknowledgments
This study was supported by a grant from Sapienza University of Rome (Progetti di Ricerca Universitaria 2011–2012).
No potential conflicts of interest relevant to this article were reported.
We thank professor John Frederick Osborn from Department of Health Sciences and Infectious Diseases, Sapienza University of Rome, for his critical review of the manuscript and for statistical support.
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