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

Ferranti, Sarah D. de; Shrader, Peter; Linton, MacRae F.; Knowles, Joshua W.; Hudgins, Lisa C.; Benuck, Irwin; Kindt, Iris; O’Brien, Emily C.; Peterson, Amy L.; Ahmad, Zahid; Clauss, Sarah; Duell, P. Barton; Shapiro, Michael D.; Wilemon, Katherine; Gidding, Samuel S.; Neal, William A.

doi:10.1016/j.jpeds.2020.09.042

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…Mean levels of untreated LDL-C were also comparable to those of other pediatric cohorts: 220 mg/dl in LIPIGEN, a range of 188–240 mg/dl in the European cohorts ( Ramaswami et al, 2020 ), and 238 mg/dl in the CASCADE-FH Registry youth participants ( de Ferranti et al, 2021 )). Moreover, also in our study population, the most common cause of FH was the presence of at least one causative pathogenic variant in the LDLR gene while the prevalence of carriers of a heterozygous causative variant on the APOB gene was 1.4%.…”

Section: Discussionsupporting

confidence: 65%

“…The characteristics of the Italian cohort are very similar to those of other pediatric cohorts, for example, in terms of the mean age at diagnosis (10 years old in LIPIGEN, a range of 8–11 years in the European cohorts ( Ramaswami et al, 2020 ), and 9 years in the CASCADE-FH Registry youth participants ( de Ferranti et al, 2021 )). In fact, in these cohorts, subjects are identified both through opportunistic screening and cascade screening starting from index cases in the family.…”

Section: Discussionmentioning

confidence: 59%

“…In the last decade, the implementation of local pathology registers allowed to focus on specific sub-groups as the one including FH subjects under 18 years ( Gazzotti et al, 2020 ; Ramaswami et al, 2020 ; de Ferranti et al, 2021 ). National registers of FH play a key role in increasing the detection of patients with FH, understanding gaps in care, and improving management and outcomes.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Gazzotti¹,

Casula²,

Bertolini³

et al. 2022

Front. Genet.

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Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Gazzotti¹,

Casula²,

Bertolini³

et al. 2022

Front. Genet.

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“…FH is a genetic disorder that is characterized by severely elevated LDL-C levels that lead to atherosclerotic plaque deposition in the coronary arteries, leading to premature coronary artery disease at an early stage of life. 17,18 Untreated men are at a 50% risk for a fatal or nonfatal coronary event by age 50 years and untreated women are at a 30% risk by age 60 years. 18,19 The Center for Disease Control and Prevention listed FH as a tier 1 genomic application, signifying increased risk of adverse health outcomes due to a genetic condition.…”

Section: Discussionmentioning

confidence: 99%

Pediatric Drug Development Studies for Familial Hypercholesterolemia Submitted to the US Food and Drug Administration Between 2007 and 2020

Park

Vishnevetskaya

Vaidyanathan

et al. 2021

The Journal of Clinical Pharma

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Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism that leads to an increased risk of developing atherosclerosis and coronary artery disease. Hypercholesterolemia in pediatric patients is typically due to FH. Treatment of pediatric FH is achieved through lifestyle modifications, lipid-modifying pharmacotherapy, and/or apheresis. The primary objective of this review is to describe the characteristics of clinical trials conducted in pediatric patients with FH with data submitted to the US Food and Drug Administration from 2007 to 2020. Of 10 trials with 8 products in pediatric FH submitted to the Food and Drug Administration, 1 product was studied in both the heterozygous and the homozygous phenotypes, 5 were studied for heterozygous hypercholesterolemia only, and 2 were studied for homozygous familial hypercholesterolemia only. Most of the trials included pediatric patients ≥10 years of age and older. Clinical trial characteristics including the primary efficacy end points between pediatric and adult trials were mostly identical. Many lipid-lowering drugs with novel mechanisms of action have been recently approved or are currently being studied. In summary, the drug treatment of hypercholesterolemia in pediatric patients is expanding beyond the use of statins, and now involves multiple mechanisms of action involving cholesterol metabolism. As younger pediatric patients are diagnosed and treated for heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia, optimizing the doses of these agents and safety studies specific to younger pediatric patients will be necessary.

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“…Universal screening of plasma lipid levels during childhood has been trialed in some parts of Japan and we expect that such trials on local universal screening will lead to a nationwide system. In addition, reverse cascade screening, in which family members are screened on the basis of child probands, and continued worldwide registry research should improve the effectiveness of finding FH [68][69][70][71][72][73][74][75][76] .…”

Section: ) Pediatric Hofhmentioning

confidence: 99%

Homozygous Familial Hypercholesterolemia

Nohara

Tada

Ogura

et al. 2021

JAT

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Early diagnosis and initiation of lipid-lowering therapy is essential for preventing development of cardiovascular complications, even in Japan where cardiovascular disease is not the leading cause of death and its prevalence among FH patients seems to be somewhat lower than in Western countries. Heterozygous FH (HeFH) patients who carry the mutated gene in a single allele have plasma LDL cholesterol (LDL-C) levels double normal or higher and may experience the first cardiovascular event as

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

Cited by 15 publications

References 27 publications

The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Pediatric Drug Development Studies for Familial Hypercholesterolemia Submitted to the US Food and Drug Administration Between 2007 and 2020

Homozygous Familial Hypercholesterolemia

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