Hyperlipidemia treatment in children: the younger, the better.

Cardiovascular disease is the leading cause of death in the United States. There is substantial evidence that the atherosclerotic process begins in childhood, with the presence of fatty streaks in the aorta by 10 years of age and in the coronary arteries by 20 years of age.1 Atherosclerotic lesions, which occur in up to 38 percent of persons with multiple risk factors, are more common in young persons with elevations in serum total cholesterol and low-density lipoprotein (LDL) levels; body mass index; and systolic and diastolic blood pressures.2-4 Furthermore, studies in adolescents have shown that mean carotid intima-media thickness measured by ultrasonography is strongly associated with cardiovascular risk factors and predictive of coronary artery disease and cerebrovascular accidents. Most of these studies evaluated persons with familial hypercholesterolemia in whom carotid intima-media thickness was increased and the rate of change was much greater than in the control population.5 The percentage of children with hyperlipidemia appears to be increasing. Data from the National Health and Nutrition Examination Survey between 1988 and 1994 found that 10 percent of adolescents had total cholesterol levels greater than 200 mg per dL (5.18 mmol per L).6 In the more recent Child and Adolescent Trial for Cardiovascular Health, 13.3 percent of children nine to 10 years of age had total cholesterol levels greater than 200 mg per dL.7 Despite no longterm studies evaluating the effectiveness of screening for dyslipidemia in childhood and its effect in delaying or reducing the incidence of cardiovascular-related events, the American Academy of Pediatrics released an updated clinical policy statement in 2008 on lipid screening and cardiovascular health in childhood. The recommendations are summarized in Table 1.8,9 The American Heart Association expert panel has also identified children at higher risk of premature atherosclerosis. These children require closer surveillance and more aggressive treatment. Children at highest risk are predicted to have symptomatic coronary artery disease before 30 years of age and include patients with homozygous familial hypercholesterolemia and type 1 diabetes mellitus.9 Additional cardiovascular risk stratification and risk reduction strategies are outlined at http://circ.ahajournals.org/ cgi/content/full/114/24/2710. Pharmacologic treatment of hyperlipidemia in children has evolved over the past decade (Table 2).8 Statins have led to significant reductions in cardiovascular and all-cause mortality for adults. As a result, there has been increasing experience with and clinical trials of statin use in children with familial hypercholesterolemia. Statins have supplanted the less effective and less tolerated bile acid sequestrants as mainstay therapy. One randomized controlled trial (n = 214; two-year study) and one recent meta-analysis (six studies; n = 798; 12 to 104 weeks of treatment) evaluating the safety and effectiveness of statins in children with familial hypercholesterolemia found no statistically significant increases in adverse events compared with placebo (relative risk = 0.99; 95% confidence interval [CI], 0.79 to 1.25). Analysis of the pooled data showed a significant 30 percent reduction in LDL cholesterol (95% CI, –36 to –24 percent). No differences were observed for muscle or liver toxicity or Tanner staging.10,11 Editorials