Effect of Rosuvastatin on Carotid IMT in HeFH Children

Study Questions:

What is impact of rosuvastatin on carotid intima-media thickness (IMT) in children with heterozygous familial hypercholesterolemia (HeFH)?


A multicenter, prospective, open-label study was performed using siblings of HeFH patients as controls. Children with HeFH aged 6 to <18 years and low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L (>190 mg/dl) or LDL-C >4.1 mmol/L (>158 mg/dl) in the setting of additional risk factors received rosuvastatin for 2 years. The starting dose was 5 mg once daily, which was escalated to 10 mg for patients aged 6 to <10 years or 20 mg for patients aged 10 to <18 years. Carotid IMT was assessed by ultrasonography at baseline, 12, and 24 months in all patients and in age-matched unaffected siblings. P-values of carotid IM measurements were adjusted for age, sex, carotid artery site, and family relations.


At baseline, mean carotid IMT was significantly greater for the 197 HeFH children (0.397 ± 0.049 mm) as compared with the 65 unaffected siblings (0.377 ± 0.045 mm, p = 0.001). During 2 years of follow-up, mean reduction in LDL-C was 41% (2.4 mmol/L [93 mg/dl]) and 38% of patients achieved the goal of <2.85 mmol/L (110 mg/dl). The rate of change in carotid IMT was lower in the HeFH patients as compared with controls (p = 0.002). The end-of-study difference in mean carotid IMT between HeFH children and unaffected siblings after 2 years was no longer significant (0.408 ± 0.043 mm and 0.402 ± 0.042 mm, respectively, p = 0.2).


Baseline carotid IMT was significantly greater in patients with HeFH as compared with unaffected siblings. Treatment with rosuvastatin resulted in a slower increase in carotid IMT in HeFH children than untreated unaffected siblings.


This study assessed the impact of rosuvastatin on carotid IMT in children with HeFH. The study demonstrated both a significant reduction in LDL-C as well as rate in change of mean carotid IMT in patients as compared with unaffected, untreated siblings. The primary limitation of the study is a lack of a true placebo control group with double-blind randomization. It was not thought to be ethical to withhold therapy with a statin in this patient population. Although statin therapy has been shown to be effective in both lowering LDL-C levels as well as slowing the rate of increase in carotid IMT, there is as of yet no firm evidence that treatment with lipid-lowering agents prevents cardiovascular events later in life. Despite this, existing data support early initiation of LDL-C reduction in children with HeFH.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Echocardiography/Ultrasound

Keywords: Carotid Intima-Media Thickness, Cholesterol, LDL, Dyslipidemias, Heart Defects, Congenital, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Hypolipidemic Agents, Primary Prevention, Risk Factors, Siblings

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