ABC | Volume 111, Nº3, September 2018

Original Article Radaelli et al Secondary dyslipidemia in obese children Arq Bras Cardiol. 2018; 111(3):356-361 Figure 1 – Flow diagram of the studies included. RCT: randomized clinical trial. Records identified through database searching n = 16793 Records after duplicates removed n = 15820 Records screened n = 15820 Records excluded n = 15740 Full-text articles assessed for eligibility n = 80 Full-text articles excluded, with reasons (n = 80) – Not pediatric (n = 39) – Not statin (n = 15) – Not RCT (n = 12) – Familial Hypercholesterolemia (n = 14) Studies included in quantitative synthesis (meta-analysis) Dyslipidemia Secondary to Obesity n = 0 Identification Screening Eligibility Included All statins recommended by the US Food and Drug Administration (FDA) 23 have been approved for children with FH and some other primary or genetic dyslipidemia causes. Data about cholesterol reduction in other groups of children were insufficient. 32 The statins used to treat children with HeFH are approved by the FDA or used in treatments based on cholesterol-lowering studies in children with HeFH. 33 For other dyslipidemia causes in children, the focus should be on the diet and treating subjacent metabolic disorders. 34 Treatment may be started earlier in severe cases. 35 Effectiveness and safety are similar in both children with genetic disorders and children with DSO in the short term. However, concerns about long-term safety still remain. 36,37 None of these studies cited above had a long-term follow up, and none of them described potential late collateral effects of early therapy for cholesterol reduction or delay in cardiovascular outcomes. 38 Kusters et al. 39 have reported the longest follow-up in children with FH treated with statins. Long-term treatment with statins started during childhood in patients with FH was associated with the normalization of the ntima-media thickness progression. No serious adverse event was reported during the 10-year follow-up. Braamskamp et al. 40 have published the first study that evaluated the long-term effect of statin treatment started in childhood on the plasma of gonadal steroid hormones, gonadotropins and dehydroepiandrosterone in young adults with FH. After 10 years of statin treatment, the concentrations of testosterone, estradiol, luteinizing hormone and follicle stimulating hormone in those patients with FH were within the reference range when compared with non-affected siblings. Before starting the widespread use of statins in children with secondary dyslipidemias, ideally studies should establish that statins can reduce total morbidity and mortality in the long-term. There must also be a logical progression of studies addressing primary prevention, from the oldest to the youngest. The use of statins for primary prevention in adults with secondary hyperlipidemia is currently under debate. The introduction of statins at an earlier age may offer the possibility of greater risk reduction than the one currently observed in studies with adults, but to this date this hypothesis remains highly speculative. Conclusions In our search, we found no randomized clinical trial addressing the use of statin therapy in children and adolescents with DSO. All studies retrieved had been performed in patients with FH. The usual practice of extrapolating findings from studies in genetic dyslipidemia ignores the differences in long-term cardiovascular risks and long-term drug treatment risks, when compared to recommendation of lifestyle changes. Randomized clinical trials are needed to understand drug treatment in secondary dyslipidemia. 358