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

Abstract

Background and aims

The triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD).

Methods and results

The study population, including 548 children (aged 6–16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08–3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03–15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30–3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62–4.56); P < 0.01].

Conclusion

TG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.

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).