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

被引:19
作者
Cuchel, Marina [1 ]
Lee, Paul C. [1 ]
Hudgins, Lisa C. [2 ]
Duell, P. Barton [3 ,4 ]
Ahmad, Zahid [5 ]
Baum, Seth J. [6 ]
Linton, MacRae F. [7 ]
de Ferranti, Sarah D. [8 ]
Ballantyne, Christie M. [9 ]
Larry, John A. [10 ]
Hemphill, Linda C. [11 ]
Kindt, Iris [12 ]
Gidding, Samuel S. [13 ]
Martin, Seth S. [14 ]
Moriarty, Patrick M. [15 ]
Thompson, Paul P. [16 ]
Underberg, James A. [17 ]
Guyton, John R. [18 ]
Andersen, Rolf L. [19 ]
Whellan, David J. [20 ]
Benuck, Irwin [21 ]
Kane, John P. [22 ]
Myers, Kelly [23 ]
Howard, William [24 ]
Staszak, David [24 ]
Jamison, Allison [23 ]
Card, Mary C. [23 ]
Bourbon, Mafalda [25 ,26 ]
Chora, Joana R. [25 ,26 ]
Rader, Daniel J. [1 ]
Knowles, Joshua W. [23 ,27 ,28 ,29 ]
Wilemon, Katherine [23 ]
McGowan, Mary P. [23 ,30 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA USA
[2] Weill Cornell Med Coll, Rogosin Inst, New York, NY USA
[3] Oregon Hlth & Sci Univ, Dept Med, Knight Cardiovasc Inst, Ctr Prevent Cardiol, Portland, OR USA
[4] Oregon Hlth & Sci Univ, Dept Med, Knight Cardiovasc Inst, Div Endocrinol Diabet & Clin Nutr, Portland, OR USA
[5] UT Southwestern Med Ctr, Dept Internal Med, Div Endocrinol, Dallas, TX USA
[6] Flourish Res, Boca Raton, FL USA
[7] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN USA
[8] Boston Children Hosp, Dept Cardiol, Boston, MA USA
[9] Baylor Coll Med, Houston, TX USA
[10] Ohio State Univ, Wexner Med Ctr, Columbus, OH USA
[11] Massachusetts Gen Hosp, Boston, MA USA
[12] DEARhealth INC, Los Angeles, CA USA
[13] Geisinger, Danville, PA USA
[14] Johns Hopkins Univ, Sch Med, Ciccarone Ctr Prevent Cardiovasc Dis, Div Cardiol,Dept Med, Baltimore, MD USA
[15] Univ Kansas, Med Ctr, Kansas City, KS USA
[16] Hartford Hosp, Hartford, CT USA
[17] NYU, Langone Med Ctr, New York, NY USA
[18] Duke Univ, Med Ctr, Dept Med, Div Endocrinol Metab & Nutr, Durham, NC USA
[19] Lancaster Gen Hlth Penn Med, Lancaster, PA USA
[20] Thomas Jefferson Univ, Philadelphia, PA USA
[21] Feinberg Sch Med, Dept Pediat, Chicago, IL USA
[22] UC San Francisco, San Francisco, CA USA
[23] Family Heart Fdn, Pasadena, CA USA
[24] Atomo Inc, Austin, TX USA
[25] Inst Nacl Saude Doutor Ricardo Jorge, Dept Promocao Saude & Prevencao Doencas Nao Trans, Grp Invest Cardiovasc, Lisbon, Portugal
[26] Univ Lisbon, Fac Ciencias, BioISI Biosyst & Integrat Sci Inst, Lisbon, Portugal
[27] Cardiovasc Inst, Div Cardiovasc Med, Dept Med, Stanford, CA USA
[28] Stanford Diabet Res Ctr, Stanford, CA USA
[29] Stanford Prevent Res Ctr, Stanford, CA USA
[30] Dartmouth Hitchcock Med Ctr, Sect Cardiovasc Med, Dept Med, Lebanon, NH USA
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2023年 / 12卷 / 09期
基金
美国国家卫生研究院;
关键词
atherosclerotic cardiovascular disease; homozygous familial hypercholesterolemia; lipid-lowering treatments; low-density lipoprotein cholesterol; xanthomas; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT; RISK REDUCTION; CHILDREN; PREVALENCE; GUIDELINES; NUTRITION; PREGNANCY; OUTCOMES; STATINS;
D O I
10.1161/JAHA.122.029175
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundHomozygous 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 ResultsData 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. ConclusionsOnly 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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