Document Type
Article
Publication Date
5-2-2023
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.
Recommended Citation
Cuchel, Marina; Lee, Paul C.; Hudgins, Lisa C.; Duell, P. Barton; Ahmad, Zahid; Baum, Seth J.; Linton, MacRae F.; de Ferranti, Sarah D.; Ballantyne, Christie M.; Larry, John A.; Hemphill, Linda C.; Kindt, Iris; Gidding, Samuel S.; Martin, Seth S.; Moriarty, Patrick M.; Thompson, Paul P.; Underberg, James A.; Guyton, John R.; Andersen, Rolf L.; Whellan, David J.; Benuck, Irwin; Kane, John P.; Myers, Kelly; Howard, William; Staszak, David; Jamison, Allison; Card, Mary C.; Bourbon, Mafalda; Chora, Joana R.; Rader, Daniel J.; Knowles, Joshua W.; Wilemon, Katherine; and McGowan, Mary P., "Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry" (2023). Division of Cardiology Faculty Papers. Paper 127.
https://jdc.jefferson.edu/cardiologyfp/127
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
PubMed ID
37119068
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons
Comments
This article is the author's final published version in the Journal of the American Heart Association, volume 12, Issue 9, 2 May 2023, Article number e029175.
The published version is available at https://doi.org/10.1161/JAHA.122.029175. Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.