Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults
Background Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants. Methods and Results Th...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-06-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.025192 |
| _version_ | 1797810228896464896 |
|---|---|
| author | Brandon K. Bellows Amit V. Khera Yiyi Zhang Natalia Ruiz‐Negrón Henry M. Stoddard John B. Wong Dhruv S. Kazi Sarah D. de Ferranti Andrew E. Moran |
| author_facet | Brandon K. Bellows Amit V. Khera Yiyi Zhang Natalia Ruiz‐Negrón Henry M. Stoddard John B. Wong Dhruv S. Kazi Sarah D. de Ferranti Andrew E. Moran |
| author_sort | Brandon K. Bellows |
| collection | DOAJ |
| description | Background Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants. Methods and Results The clinical characteristics and FH variant status of 49 738 UK Biobank participants were used to develop a regression model to predict the probability of having any FH variants. The regression model and modified Dutch Lipid Clinic Network criteria were applied to 39 790 adult participants (aged ≥20 years) in the National Health and Nutrition Examination Survey to estimate the yield of FH screening programs using Dutch Lipid Clinic Network clinical criteria alone (excluding genetic variant status), genetic testing alone, or combining clinical criteria with genetic testing. The regression model accurately predicted FH variant status in UK Biobank participants (observed prevalence, 0.27%; predicted, 0.26%; area under the receiver‐operator characteristic curve, 0.88). In the National Health and Nutrition Examination Survey, the estimated yield per 1000 individuals screened (95% CI) was 3.7 (3.0–4.6) FH cases with the Dutch Lipid Clinic Network clinical criteria alone, 3.8 (2.7–5.1) cases with genetic testing alone, and 6.6 (5.3–8.0) cases by combining clinical criteria with genetic testing. In young adults aged 20 to 39 years, using clinical criteria alone was estimated to yield 1.3 (95% CI, 0.6–2.5) FH cases per 1000 individuals screened, which was estimated to increase to 4.2 (95% CI, 2.6–6.4) FH cases when combining clinical criteria with genetic testing. Conclusions Screening for FH using a combination of clinical criteria with genetic testing may increase identification and the opportunity for early treatment of individuals with FH. |
| first_indexed | 2024-03-13T07:06:04Z |
| format | Article |
| id | doaj.art-fb9dc50b5cab461f9147af0d42850f30 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-13T07:06:04Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-fb9dc50b5cab461f9147af0d42850f302023-06-06T12:11:51ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-06-01111110.1161/JAHA.121.025192Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US AdultsBrandon K. Bellows0Amit V. Khera1Yiyi Zhang2Natalia Ruiz‐Negrón3Henry M. Stoddard4John B. Wong5Dhruv S. Kazi6Sarah D. de Ferranti7Andrew E. Moran8Department of Medicine Columbia University New York NYCenter for Genomic Medicine Massachusetts General Hospital Boston MADepartment of Medicine Columbia University New York NYDepartment of Pharmacotherapy University of Utah Salt Lake City UTDepartment of Medicine Columbia University New York NYDepartment of Medicine Tufts Medical Center Boston MADepartment of Medicine Harvard Medical School Boston MADepartment of Pediatrics Harvard Medical School Boston MADepartment of Medicine Columbia University New York NYBackground Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants. Methods and Results The clinical characteristics and FH variant status of 49 738 UK Biobank participants were used to develop a regression model to predict the probability of having any FH variants. The regression model and modified Dutch Lipid Clinic Network criteria were applied to 39 790 adult participants (aged ≥20 years) in the National Health and Nutrition Examination Survey to estimate the yield of FH screening programs using Dutch Lipid Clinic Network clinical criteria alone (excluding genetic variant status), genetic testing alone, or combining clinical criteria with genetic testing. The regression model accurately predicted FH variant status in UK Biobank participants (observed prevalence, 0.27%; predicted, 0.26%; area under the receiver‐operator characteristic curve, 0.88). In the National Health and Nutrition Examination Survey, the estimated yield per 1000 individuals screened (95% CI) was 3.7 (3.0–4.6) FH cases with the Dutch Lipid Clinic Network clinical criteria alone, 3.8 (2.7–5.1) cases with genetic testing alone, and 6.6 (5.3–8.0) cases by combining clinical criteria with genetic testing. In young adults aged 20 to 39 years, using clinical criteria alone was estimated to yield 1.3 (95% CI, 0.6–2.5) FH cases per 1000 individuals screened, which was estimated to increase to 4.2 (95% CI, 2.6–6.4) FH cases when combining clinical criteria with genetic testing. Conclusions Screening for FH using a combination of clinical criteria with genetic testing may increase identification and the opportunity for early treatment of individuals with FH.https://www.ahajournals.org/doi/10.1161/JAHA.121.025192cardiovascular diseasediagnostic screeningfamilial hypercholesterolemialipids |
| spellingShingle | Brandon K. Bellows Amit V. Khera Yiyi Zhang Natalia Ruiz‐Negrón Henry M. Stoddard John B. Wong Dhruv S. Kazi Sarah D. de Ferranti Andrew E. Moran Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular disease diagnostic screening familial hypercholesterolemia lipids |
| title | Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults |
| title_full | Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults |
| title_fullStr | Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults |
| title_full_unstemmed | Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults |
| title_short | Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults |
| title_sort | estimated yield of screening for heterozygous familial hypercholesterolemia with and without genetic testing in us adults |
| topic | cardiovascular disease diagnostic screening familial hypercholesterolemia lipids |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.025192 |
| work_keys_str_mv | AT brandonkbellows estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT amitvkhera estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT yiyizhang estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT nataliaruiznegron estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT henrymstoddard estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT johnbwong estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT dhruvskazi estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT sarahddeferranti estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults AT andrewemoran estimatedyieldofscreeningforheterozygousfamilialhypercholesterolemiawithandwithoutgenetictestinginusadults |