SEARCHCOHORTcardiology, endocrinology

cohort·cardiology, endocrinology, pediatrics, epidemiology, internal medicine·PMC10227232

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

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease · 33 authors, 28 centres

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TL;DR

This observational cohort study analyzed 67 children and adults with HoFH from the CASCADE FH Registry across 20 US lipid specialty clinics and queried a payer database of over 81 million individuals.

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This observational cohort study analyzed data from 67 adults and children with clinically diagnosed HoFH enrolled in the CASCADE FH Registry across 20 US lipid specialty clinics, with genetic confirmation in 43 patients. The investigators also queried the Family Heart Database, a US payer database of over 81 million individuals, to identify real-world cases with lipid profiles similar to genetically confirmed HoFH patients. Untreated LDL-C levels were significantly higher in children than adults (776 versus 533 mg/dL; P=0.001), suggesting that only the most severely affected are diagnosed early. The Family Heart Database query identified 277 individuals with HoFH-like profiles, of whom 40% were on no lipid-lowering treatment and only 18% had advanced lipid-lowering treatments prescribed.

STUDY TYPE

cohort

SPECIALTY

cardiology

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ORIGINAL PAPER

PMC10227232

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

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

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ABSTRACT

Abstract 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. Keywords: atherosclerotic cardiovascular disease, homozygous familial hypercholesterolemia, lipid‐lowering treatments, low‐density lipoprotein cholesterol, xanthomas Subject Categories: Quality and Outcomes, Lipids and Cholesterol

CITATION EXPORT

Marina Cuchel, Paul C Lee, Lisa C Hudgins et al.. Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease. (2023). https://doi.org/10.1161/JAHA.122.029175

AUTHORS

33 · 28 CENTRES

Marina Cuchel, Paul C Lee, Lisa C Hudgins, P Barton Duell, Zahid Ahmad, Seth J Baum, MacRae F Linton, Sarah D de Ferranti, Christie M Ballantyne, John A Larry, Linda C Hemphill, Iris Kindt, Samuel S Gidding, Seth S Martin, Patrick M Moriarty, Paul P Thompson, James A Underberg, John R Guyton, Rolf L Andersen, David J Whellan, Irwin Benuck, John P Kane, Kelly Myers, William Howard, David Staszak, Allison Jamison, Mary C Card, Mafalda Bourbon, Joana R Chora, Daniel J Rader, Joshua W Knowles, Katherine Wilemon, Mary P McGowan

1 Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
2 The Rogosin Institute/Weill Cornell Medical College, New York, NY
3 Center for Preventive Cardiology, Knight Cardiovascular Institute, and Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland, OR
4 Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
5 Flourish Research, Boca Raton, FL
6 Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
7 Department of Cardiology, Boston Children Hospital, Boston, MA
8 Baylor College of Medicine, Houston, TX
9 Ohio State University Wexner Medical Center, Columbus, OH
10 Massachusetts General Hospital, Boston, MA
11 DEARhealth INC. Los Angeles, CA
12 Geisinger, Danville, PA
13 Division of Cardiology, Department of Medicine, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD
14 University of Kansas Medical Center, Kansas City, KS
15 Hartford Hospital, Hartford, CT
16 NYU Langone Medical Center, New York, NY
17 Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC
18 Lancaster General Health/Penn Medicine, Lancaster, PA
19 Thomas Jefferson University, Philadelphia, PA
20 Department of Pediatrics, Feinberg School of Medicine, Chicago, IL
21 UC San Francisco, San Francisco, CA
22 Family Heart Foundation, Pasadena, CA
23 Atomo Inc. Austin, TX
24 Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa AND BioISI–Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
25 Division of Cardiovascular Medicine, Department of Medicine, Cardiovascular Institute, Stanford, CA
26 Stanford Diabetes Research Center, Stanford, CA
27 Stanford Prevention Research Center, Stanford, CA
28 Department of Medicine, Section of Cardiovascular Medicine, Dartmouth‐Hitchcock Medical Center, Lebanon, NH