Molecular Aspects Of Homozygous Familial Hypercholesterolemia In Ibero-American Countries

Alves, Ana Catarina; Alonso, Rodrigo; Cuevas, Ada; Medeiros, Ana Margarida; Pereira, Alexandre C.; Jannes, Cinthia E.; Krieger, José Eduardo; Arroyo, Raquel; Schreier, Laura; Corral, Pablo; Bañares, V.; Araujo, Gomes; Asenjo, Sylvia; Stoll, Mario; Dell’Oca, Nicolás; Reyes, Ximena; Ressia, A.; Campo, Rafael; Merchán, Alonso; Teresa, Mazurczak-Pluta; Vasques-Cardenas, A.; Mata, Nelva; Santos, Raúl D.; Bourbon, Mafalda

doi:10.1016/j.atherosclerosis.2019.06.654

Cited by 6 publications

(10 citation statements)

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“…Our results are consistent with various other studies examining phenotypic variability in response to LLTs in patients with HoFH. 2 , 11 , 12 , 14 The availability of new highly effective therapeutic approaches, such as the recently approved evinacumab, provides optimism about the ability to bring these patients to their LDL‐C goals. 26 Of the 6 adults who entered an open‐label study in which they received evinacumab while enrolled in the CASCADE FH Registry, the observed dramatic 50% LDL‐C lowering was consistent with published data 26 and was far greater than the typically modest LDL‐C lowering achieved with most LDL‐C–lowering medications in patients with HoFH.…”

Section: Discussionmentioning

confidence: 99%

“…Historically, HoFH has been diagnosed clinically in patients with untreated LDL‐C levels ≥500 mg/dL, xanthomas before the age of 10 years, or both parents with a phenotype consistent with heterozygous FH. 1 However, increased use of genetic diagnosis and large cohort studies have highlighted the broad phenotypic spectrum of genetically diagnosed HoFH with LDL‐C levels below the historically used cutoff, 1 , 2 , 3 , 9 , 10 , 11 , 12 prompting a proposal for a less stringent threshold for untreated LDL‐C levels. 13 …”

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confidence: 99%

“…Results from the HICC (HoFH International Clinical Collaborators) registry, including data on 751 patients with HoFH, confirm that HoFH remains underdiagnosed and undertreated worldwide. 1 , 3 , 11 Although characteristics and treatment patterns of cohorts with HoFH from Europe, South Africa, and Japan have been published, 2 , 10 , 11 , 12 , 14 , 15 there is little information on the health status of patients with HoFH in the United States, where awareness of HoFH clinical characteristics, diagnostic and therapeutic guidelines, and access to lipid specialists remain suboptimal. 16 …”

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confidence: 99%

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

Cuchel

Lee

Hudgins

et al. 2023

JAHA

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

Cuchel

Lee

Hudgins

et al. 2023

JAHA

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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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“…1,2 Based on the reported prevalence of heterozygous FH (HeFH) as ≈1 in 300 and more recent data of genetically identified HoFH cases in regional FH registries, the true prevalence of HoFH may be closer to 1:200 000 to 450 000. [5][6][7][8] This suggests that some patients with HoFH may not be clinically recognized. This likely relates to the spectrum of clinical severity of HoFH, which can overlap with that of HeFH.…”

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confidence: 99%

Genetic Identification of Homozygous Familial Hypercholesterolemia by Long-Read Sequencing Among Patients With Clinically Diagnosed Heterozygous Familial Hypercholesterolemia

Chaudhry¹,

Trinder²,

Veselý³

et al. 2023

Circ: Genomic and Precision Medicine

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Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma LDL-C (low-density lipoprotein cholesterol) and accelerated atherosclerosis. Accurate identification of patients with HoFH is essential as they may be eligible for specialized treatments. We hypothesized that a subset of patients with clinically diagnosed heterozygous FH (HeFH) may in fact have HoFH, and this could be identified by genetic diagnosis. Methods: We recruited patients with a clinical diagnosis of HeFH based on a Dutch Lipid Clinic Network score ≥6 and no secondary cause of hypercholesterolemia. We performed targeted next-generation sequencing of the LDLR , APOB , PCSK9 , and LDLRAP1 genes, followed by long-read sequencing of the LDLR gene in patients with >1 pathogenic LDLR variant. We examined lipid levels and cardiovascular events. Results: Among 705 patients with clinically diagnosed HeFH, we identified a single pathogenic variant in 300 (42.6%) and >1 pathogenic variant in the LDLR gene in 11 patients (1.6%). We established a genetic diagnosis of HoFH in 6 (0.9%) patients (3 true homozygotes and 3 compound heterozygotes). The mean baseline LDL-C and prevalence of premature cardiovascular disease of patients with genetically identified HoFH was significantly higher than patients with HeFH. Conclusions: In a cohort of patients with clinically diagnosed HeFH, genetic testing including long-read sequencing revealed that 0.9% had HoFH. These patients tended to have a more severe clinical phenotype. Genetic testing of patients with clinical FH may identify patients with HoFH that had eluded clinical diagnosis.

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Molecular Aspects Of Homozygous Familial Hypercholesterolemia In Ibero-American Countries

Cited by 6 publications

References 0 publications

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

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

Homozygous Familial Hypercholesterolemia

Genetic Identification of Homozygous Familial Hypercholesterolemia by Long-Read Sequencing Among Patients With Clinically Diagnosed Heterozygous Familial Hypercholesterolemia

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