Hypercholesterolemia: McCrindle BW

Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, Parekh RS, Steinberger J, Anonymous00343, Anonymous00344, Anonymous00345, Anonymous00346, Anonymous00347, Anonymous00348, Anonymous00349, Anonymous00350, Anonymous00351. · No affiliation provided · J Cardiovasc Nurs. · Pubmed #17545824 No free full text.

Abstract: Although for most children the process of atherosclerosis is subclinical, dramatically accelerated atherosclerosis occurs in some pediatric disease states, with clinical coronary events occurring in childhood and very early adult life. As with most scientific statements about children and the future risk for cardiovascular disease, there are no randomized trials documenting the effects of risk reduction on hard clinical outcomes. A growing body of literature, however, identifies the importance of premature cardiovascular disease in the course of certain pediatric diagnoses and addresses the response to risk factor reduction. For this scientific statement, a panel of experts reviewed what is known about very premature cardiovascular disease in 8 high-risk pediatric diagnoses and, from the science base, developed practical recommendations for management of cardiovascular risk.

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.

Hayman LL, Williams CL, Daniels SR, Steinberger J, Paridon S, Dennison BA, McCrindle BW, Anonymous00360. · No affiliation provided · Circulation. · Pubmed #15477426 links to  free full text

This publication has no abstract.

McCrindle BW, Ose L, Marais AD. · Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. · J Pediatr. · Pubmed #12915827 No free full text.

Abstract: OBJECTIVE: To determine the safety and efficacy of atorvastatin (10 to 20 mg) in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. STUDY DESIGN: Subjects (n=187) were randomly assigned to 26 weeks of treatment with atorvastatin (10 mg) or placebo. Dosage was increased to 20 mg if LDL cholesterol (LDL-C) levels remained >3.4 mmol/L (130 mg/dL) at week 4. At week 26, subjects received 10 mg of atorvastatin for an additional 26 weeks. Efficacy variables included percent changes in LDL-C, total cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B from baseline to week 26. RESULTS: Atorvastatin caused a highly significant reduction in LDL-C compared with placebo (-40% vs -0.4%, respectively; P<.001). Percent changes at week 26 also significantly favored atorvastatin for total cholesterol (-32% vs -1.5%; P<.001), triglycerides (-12% vs +1.0%; P=0.03), and apolipoprotein B (-34% vs +0.7%; P<.001), with a significantly greater increase in HDL cholesterol with atorvastatin compared with placebo (+2.8% vs -1.8%; P=.02). Atorvastatin was as well-tolerated as placebo. CONCLUSIONS: Treatment with atorvastatin for 12 months was effective and safe for pediatric subjects with known familial hypercholesterolemia or severe hypercholesterolemia.

McCrindle BW, Helden E, Cullen-Dean G, Conner WT. · Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. · Pediatr Res. · Pubmed #12032266 No free full text.

Abstract: We sought to determine whether a low-dose combination of a bile acid-binding resin (colestipol) with an hydroxymethylglutaryl CoA reductase inhibitor (pravastatin) would result in improved acceptability, compliance, and effectiveness in lipid-lowering compared with conventional therapy with a higher dose of a bile acid-binding resin only, with fewer side effects. We performed a randomized, crossover open-label clinical trial with two 18-wk medication regimens separated by an 8-wk washout period in 36 children and adolescents with familial hypercholesterolemia or familial combined hyperlipidemia. The regimens included colestipol 10 g/d (10 pills) versus a combination of colestipol 5 g/d with pravastatin 10 mg/d (six pills). All patients were maintained on a fat-reduced diet. Acceptability was better with the combination regimen. Mean compliance was similar and suboptimal (approximately 60%) with all medication components. Mean relative LDL cholesterol lowering was significantly better with the combination regimen (-17 +/- 16% versus -10 +/- 13%; p = 0.045), although insufficient to achieve recommended target values in the majority of patients on either regimen. Both regimens were equally free of adverse effects, with no important effect on chemistry or hematologic values. Patient-reported adverse effects were more common with the conventional-dose colestipol-only regimen. Compliance with medication regimens using the bile acid-binding resins is suboptimal, although combination with a low dose of a statin may result in better lipid lowering.

Manlhiot C, Larsson P, Gurofsky RC, Smith RW, Fillingham C, Clarizia NA, Chahal N, Clarke JT, McCrindle BW. · Division of Cardiology, Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. · Pediatrics. · Pubmed #19171610 No free full text.

Abstract: OBJECTIVES: The prevalence and identification of hypertriglyceridemia in youths will likely will increase in the future as a consequence of childhood obesity and increased screening for dyslipidemias. We sought to review our clinical experience with hypertriglyceridemia, evaluate factors associated with increased triglyceride levels, and review treatment options to provide guidance for management. METHODS: Clinical review of data for all patients who had > or =1 elevated triglyceride level (>4 mmol/L [>350 mg/dL]) while being monitored in a specialized lipid disorders clinic was performed. RESULTS: The study population consisted of 76 patients with 761 clinic visits. Hypertriglyceridemia was secondary to lifestyle factors for 13 patients. The rest had primary hypertriglyceridemia, with 32 patients having familial combined hypertriglyceridemia and hypercholesterolemia (type II), 25 patients having primary hypertriglyceridemia (type IV), 4 patients having familial lipase deficiency (type I), and 2 patients having hyperlipoproteinemia E2/E2 phenotype (type III). Triglyceride levels were highest in type I and III hypertriglyceridemia (>10 mmol/L [>900 mg/dL]), followed by type IV and adiposity-related hypertriglyceridemia (>4 mmol/L [>350 mg/dL]) and finally type II familial combined hypertriglyceridemia and hypercholesterolemia (>2 mmol/L [>180 mg/dL]). A total of 34 patients received 37 trials of drug therapy as part of triglyceride level management (bile acid-binding resins, n = 12; fibrates, n = 19; statins, n = 6). Triglyceride levels were found to decrease over time with the use of fibrates, to increase with the use of bile acid-binding resins, and not to change with the use of statins. CONCLUSIONS: Lifestyle modifications remain the primary therapeutic avenue for the management of pediatric hypertriglyceridemia. We propose an algorithm for the management of this heterogeneous population to guide clinicians in their treatment decisions.

Kolansky DM, Cuchel M, Clark BJ, Paridon S, McCrindle BW, Wiegers SE, Araujo L, Vohra Y, Defesche JC, Wilson JM, Rader DJ. · Cardiovascular Medicine Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. · Am J Cardiol. · Pubmed #19026292 No free full text.

Abstract: Homozygous familial hypercholesterolemia (hoFH) is caused by mutations in the low-density lipoprotein receptor gene and is characterized by severe hypercholesterolemia from birth and onset of premature cardiovascular disease (CVD) during childhood. The onset and progression of CVD using currently available testing methods in children with hoFH have not been fully characterized. A large cohort of patients with hoFH referred to our subspecialty clinic was studied. Thirty-nine patients (22 aged < or =16 years) underwent extensive cardiovascular, lipid, and genetic evaluation. Sixteen children < or =16 years without known CVD when first evaluated were followed up longitudinally for up to 8 years. CVD was clinically evident in 88% of subjects aged >16 years and 9% of those < or =16 years. Markers of atherosclerosis correlated significantly with age at which lipid-lowering treatment was initiated (abnormal coronary angiogram, abnormal aortic valve using echocardiography, and high calcium score using electron beam computed tomography; all p <0.01; abnormal carotid Doppler result; p = 0.03). Twenty of 22 children had no clinical evidence of coronary artery disease, yet 7 of these children had angiographically confirmed mild coronary artery disease (<50%) and 8 had mild to moderate aortic regurgitation using echocardiography. Of noninvasive tests, only evaluation of aortic valve regurgitation using echocardiography predicted the presence of angiographic coronary stenosis (p <0.001). During follow-up, 7 children developed progression of coronary and/or aortic valvular disease during their teenage years and 4 required surgical interventions. In conclusion, in these patients aggressive lipid-lowering treatment initiated in early childhood is warranted. Careful coronary and valvular surveillance strategies and coronary revascularization when appropriate are also warranted in this high-risk population.

Al-Shaikh AM, Abdullah MH, Barclay A, Cullen-Dean G, McCrindle BW. · Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Ontario, Canada. · Cardiol Young. · Pubmed #12018713 No free full text.

Abstract: OBJECTIVE: To relate clinical factors to the development of cardiovascular atherosclerosis for patients with homozygous familial hypercholesterolemia. BACKGROUND: Homozygous familial hypercholesterolemia is associated with extreme elevations in levels of cholesterol causing aggressive atherosclerosis. METHODS: We reviewed 10 children, 8 of whom were male, assessed at a single institution. We found that individual characteristics, levels of lipid, cardiovascular investigations, and management were related to the activity of low density lipoprotein receptors. RESULTS: Activity of low density lipoprotein receptors was defined as absent, being less than 2% of normal, in 4 patients who presented at the ages of 0.3, 1.4, 1.8, and 4.5 years, respectively. The activity was minimal, representing 5%-30% of normal, in another 4 patients presenting at the ages of 6.1, 9.6, 9.9, and 12 years, and was undetermined in 2 patients who presented at the ages of 3.5, and 12.1 years. Levels of low density lipoprotein cholesterol at presentation ranged from 12.2 to 24 millimoles per litre. Plasmapheresis was performed bi-weekly in 9 patients. Patients with absence of receptor activity were less likely to have a serial decrease in the levels of low density lipoprotein cholesterol prior to plasmapheresis, and one of these patients was increased to weekly plasmapheresis. In addition, they had more aggressive cardiovascular involvement of the coronary arteries, aortic valve and aorta, requiring surgical intervention at the age of 8 and 12 years in 2 patients, with sudden death at the age of 3.1 years in one patient. In contrast, 1 patient with minimal receptor activity had surgical intervention at the age of 16.6 years and another patient died suddenly at the age of 33.6 years. CONCLUSION: Complete cardiac assessment is recommended at presentation. The frequency of plasmapheresis should be adjusted according to the activity of low density lipoprotein receptors and the individual response of the patient.