Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Characteristics of Children Referred to a Lipid Clinic Before and After the Universal Screening Guidelines.

In 2011, universal lipid screening was recommended for children aged 9 to 11 years; the impact of this recommendation on the lipid clinic setting is unknown. We examined the rate of primary and secondary dyslipidemia diagnoses in a lipid clinic before (2010-2011) and after (2012-2015) the guideline recommendation. We conducted a retrospective study of new clinic patients aged 0 to 20 years seen between April 2010 and April 2015. Chi-square testing was applied. The 345 subjects were 58% males; 48% ≥13 years; 56% Hispanic; and 59% obese. There was no difference in the rate of dyslipidemia diagnoses between periods (before: primary 23%, secondary 73%, no dyslipidemia 4% vs after: 22%, 72%, 6%, respectively; P = .616). There was no significant difference between periods in subject demographics for the total sample, but among those with primary dyslipidemia, pre- to post-guideline percentage of subjects with public insurance decreased (71% to 39%; P = .006). Additional strategies to increase identification of children with dyslipidemia are needed.

Preserving Optimal Cardiovascular Health in Children.

The origins of cardiovascular disease are at the beginning of life, and national guidelines recommend evaluation for cardiovascular risk factors such as obesity and hypertension as part of general pediatric care. In this review, a simple plan is proposed for clear and consistent monitoring and messaging throughout childhood, based on the American Heart Association's "cardiovascular health" construct. A framework is provided for age-appropriate scoring of the cardiovascular health components, including diet, physical activity and screen time, sleep, smoking exposure, body mass index, blood pressure, cholesterol, and glucose. Guidance is provided for evidence-based, efficient intervention by pediatric clinicians to preserve or restore cardiovascular health. Finally, anticipated near-term advances in pediatric cardiovascular health promotion are previewed. [Pediatr Ann. 2018;47(12):e479-e486.].

Progressive Aortic Stenosis in Homozygous Familial Hypercholesterolemia After Liver Transplant.

Early onset coronary artery disease and aortic calcifications are characteristic features of patients with homozygous familial hypercholesterolemia. Standard medical therapy includes dietary modification, pharmacotherapy, and lipoprotein apheresis to lower serum low-density lipoprotein cholesterol (LDL-C). Liver transplant is a surgical option for the treatment of homozygous familial hypercholesterolemia and can lead to normal cholesterol levels. Vascular calcifications are known to progress despite standard medical therapy and have been reported after liver transplant in the setting of rejection. We present the first report of progressive severe aortic valve stenosis in a patient despite liver transplant with normalization of lipid levels and no history of graft rejection.

Point: The rationale for universal lipid screening and treatment in children.

Screening a healthy population for future harmful diseases has the potential of reducing the risk of later morbidity and mortality with early identification and intervention. However, it is important that the screening meets acceptable standards, and the benefits of the screening outweigh risks. The recently published "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents" (National Heart Lung Blood Institute Guidelines) carefully examined the multiple risk factors for coronary artery disease that begins in childhood but may not become problematic until years later. The evidence-based guidelines give many recommendations that are focused on identification, prevention, and intervention. Included in the guidelines are useful suggestions for improving lifestyle and food choices. In the section on lipids and lipoprotein, careful consideration was given to universal screening of children between 9 and 11 years of age with no known cardiac risk factors and again, if needed, between 17 and 21 years of age. Children with cardiac risk factors may be screened earlier. The section continues with rationale for medical management of children who are refractory to other interventions. The purpose of this article is to discuss the benefits of screening for dyslipidemia in the pediatric population and when necessary, medical management to reduce the risk for coronary artery disease. Both universal screening and early intervention in the pediatric population will identify individuals not previously recognized at risk for premature coronary artery disease and stroke and reduce the incidence of later morbidity and mortality.

Influences on parents' decisions for home and automobile smoking bans in households with smokers.

OBJECTIVE: To understand clinician influence on use of home and automobile smoking bans in homes of children living with a smoker. METHODS: Parents were surveyed on tobacco use, smoking bans, demographics and opinions about tobacco, including harm from environmental tobacco smoke (ETS). Responses from 463 diverse households with smokers were analyzed. RESULTS: 42% of respondents smoked; 50% had a home smoking ban and 58% an automobile smoking ban. Nonsmokers living with a smoker, those who strongly agreed in ETS harm, and those having a child < or = 5 years more often had a home smoking ban. Those recalling their child's doctor ever asking the respondent about their smoking status and African American respondents less frequently had a home ban. Automobile smoking bans were more often held by those with strong agreement in ETS harm and less often found in families having a child receiving Medicaid/uninsured. CONCLUSIONS: Having a strong perception of harm from ETS exposure was associated with having smoking bans. Aspects of health encounters not measured by this study may be negatively influencing adoption of home smoking bans or lead to recall bias. PRACTICE IMPLICATIONS: Clinicians should examine the strength, focus, and response to their messages to parents about tobacco.

Tobacco, heart disease, and practical counseling.

As a large part of the care for children is preventive health, knowledge about the effects of tobacco exposure, risk factors, prevention strategies, and intervention are important. Because most smokers begin smoking while being cared for by physicians who care for children, pediatricians are particularly well suited to identify those at risk and to provide meaningful prevention. As physicians, we need to also assist parents to quit smoking, thereby setting a good example to their children, while improving their health as well as that of their children. Likewise, when identifying a youth experimenting or regularly smoking tobacco, intervention needs to be offered through counseling, referral, or medical therapy.