ABC | Volume 111, Nº3, September 2018

Original Article Radaelli et al Secondary dyslipidemia in obese children Arq Bras Cardiol. 2018; 111(3):356-361 and LILACS. The search strategy included the terms: "Child", "Adolescent", "Hypercholesterolemia", "Dyslipidemias", "Cholesterol", "Hydroxymethylglutaryl-Coa reductase inhibitors", "Statin", “HDL-C” and “Triglycerides”. Two reviewers (G.R. and G.S.) performed the literature search and study selection independently. Disagreements were solved by consensus or by a third reviewer (L.C.P.). Selection criteria Types of study: Randomized clinical trials describing statin therapy for children and adolescents. Participants: children and adolescents (up to 18 years old). Interventions: statins for at least 8 weeks. Target condition: DSO. Outcomes: reduction in the risk factors, TC, LDL-C, apolipropotein B (APOB) and HDL-C, improvement in the coronary artery disease indirect markers and/or clinical outcomes in adult life. Search limits: Language: no language restriction. Time period: from inception to February 2016. Design: Randomized clinical trials. Main outcome: risk factors reduction in the infancy, improvement of coronary artery disease indirect markers in clinical outcomes of adult life. Secondary outcomes: statin effects - elevated plasmatic levels of TC, LDL-C and APOB, decrease in the HDL-C levels. Inclusion criteria: Randomized clinical trial reporting children with statin treatment for at least 8 weeks. Exclusion criteria: Non-blinded treatment duplicated data or absent reporting of considered outcomes. Data extraction and quality evaluation: The CONSORT analysis instrument was used to evaluate methodological quality of the included studies performed by two independent reviewers. Results We identified 16793 citations from the electronic search of the databases from inception to February 2016. After duplicate studies were removed, 15820 studies were subjected to title and abstract screening. We excluded 15740 studies and 80 studies were subjected to full-text review. We did not include any randomized clical trial about DSO in children, and all 80 articles of full-texts were excluded for the reasons: 39 studies on non-pediatric population (subjects aged 18 to 80 years), 15 studies did not use treatment with statins, 12 studies did not have the design of a randomized clinical trial, and 14 randomized clinical trials evaluated children and adolescents with familial hypercholesterolemia (FH), involving a total of 2347 individuals (Figure 1). Discussion Dyslipidemia secondary to obesity in children and adolescents is increasingly prevalent in clinical practice. However, the present review did not retrieve specific evidence about drug therapy in this group. In this type of dyslipidemia, the most common lipid alterations are low HDL-C and elevated triglycerides (TG) secondary to insulin resistance syndrome. 7 High TC levels may be associated with these conditions, but cannot be considered the most important factor. Steinberg et al. 8 showed that the degree of insulin resistance explains a significant proportion of variation in the levels of TG, LDL-C, and HDL-C, and Stan et al. 9 estimated a 10% prevalence of small dense LDL (sdLDL) particles in children showing insulin resistance compared to 1% in those without insulin resistance. As recommended by the Expert Panel, 5 low saturated-fat and cholesterol diet is the first approach to lower TC and LDL-C levels, to reduce obesity and insulin resistance, and to prevent the development of atherosclerosis. These recommendations 8 confirm that primary prevention in children with dyslipidemia involves lifestyle modification. In childhood, the construction of healthy eating habits must be emphasized, since early preference patterns have a long-term influence on dietary intake later in life. 10,11 To provide information about nutrition is, therefore, an important part of the routine visits. 12,13 However, neither assessment of the patient’s nutritional status nor discussion of dietary habits seem to be performed systematically. 14 Physicians often point to the lack of knowledge in this area as one of the main limitations to this practice. 15-17 On the other hand, obese children may also suffer from FH, that is phenotypically diagnosed by the presence of high levels of LDL-C and a family history of premature cardiovascular disease and/or high cholesterol at baseline in one of the parents and/or a mutation that causes FH. 18-20 After dietary intervention, any child with LDL-C ≥ 5 mmol/L (190 mg/dL) has high probability of having genetic FH. A family history of premature cardiovascular disease in close relatives and/or high cholesterol levels at baseline in a parent, LDL-C ≥ 4 mmol/L (160 mg/dL) are also indicative of a high probability of genetic FH. The detection of a pathogenic mutation, usually in the LDLR gene, is the gold-standard diagnosis test for FH. The LDL-C levels must be measured at least twice in 3 months to confirm the diagnosis of FH. 21 The maintenance of a healthy lifestyle and statin treatment (age 8 to 10 years) are proposed as the main interventions to control heterozygous FH (HeFH). The target of LDL-C for children is 3.5 mmol/L (130 mg/dL) if > 10 years old, or, ideally, to reduce 50% of the baseline level among children aged 8 to 10 years, especially with an extremely high LDL-C, high levels of lipoprotein(a), family history of premature cardiovascular disease or others cardiovascular risk factors, balanced against the risk of long-term adverse effect of treatment. 18,21-23 Statins have shown better effects on major cardiovascular outcomes, justifying their use despite their still unknown side effects when used for more than 2 years in children. 24 The inhibitors of HMG-CoA reductase have shown repeatedly in random controlled studies to effectively reduce coronary morbidity and mortality in adults at high risk. As a result, statins have become one of the most prescribed drugs for adults in the world. 25 In adults, statins have proved to effectively reduce both LDL-C levels and vascular events. 26,27 At usual doses, statins are a remarkably safe drug group. Few reports exist about serious adverse gastrointestinal events, and hepatic transaminases and creatine-phosphokinase elevation. However, evidence for their use in children still lacks. 28 Children with serious lipid abnormalities due to genetic disorders may meet the criteria for drug therapy with the statins commonly used in adults. In the last few years, reports about the short-term safety of some of these drugs in this group have been published. 29-31 357