Hypercholesterolemia: Jacobson MS

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, Hayman LL, Daniels SR, Anonymous00137, Anonymous00138, Anonymous00139. · Hospital for Sick Children, Toronto, Canada. · Circulation. · Pubmed #17377073 links to  free full text

Abstract: Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Jenssen BP, Jacobson MS. · University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 40, Rochester, NY 14642, USA. · Adolesc Med State Art Rev. · Pubmed #19227389 No free full text.

Abstract: Coronary artery disease is the most common cause of death in the United States and the leading cause of hospital-related health care costs. Hypercholesterolemia is a leading risk factor for cardiovascular disease, and both genetic and environmental factors affect cholesterol levels. Although the clinical symptoms and signs of elevated cholesterol levels in children do not occur until adulthood, arterial dysfunction and plaque formation begin much earlier. Thirty-six percent of US youth have a cholesterol level that is higher than normal (>170 mg/dL), with elevated low-density lipoprotein levels associated with atherosclerotic lesions and ultimate disease. Because the disease process begins in childhood and adolescence, early prevention in childhood is critically important. Currently, universal cholesterol screening of adolescents is the most cost-effective method of identifying individuals with familial hypercholesterolemia who need intensive and early preventive care.

Stein EA, Illingworth DR, Kwiterovich PO, Liacouras CA, Siimes MA, Jacobson MS, Brewster TG, Hopkins P, Davidson M, Graham K, Arensman F, Knopp RH, DuJovne C, Williams CL, Isaacsohn JL, Jacobsen CA, Laskarzewski PM, Ames S, Gormley GJ. · Medical Research Laboratories, Highland Heights, KY, USA. · JAMA. · Pubmed #9917116 links to  free full text

Abstract: CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.