Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study
To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipopr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-08-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | http://www.mdpi.com/2075-4426/8/3/27 |
| _version_ | 1797935283300204544 |
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| author | Iftikhar J. Kullo Kent R. Bailey |
| author_facet | Iftikhar J. Kullo Kent R. Bailey |
| author_sort | Iftikhar J. Kullo |
| collection | DOAJ |
| description | To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of LDLR, APOB, and PCSK9 and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score ≥ 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3–5, no pathogenic variant). We will enroll 50 patients with definite FH by recruiting an additional 26 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C > 155 mg/dL (>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case. The proposed clinical trial will compare the yield and cost of cascade screening for FH patients with/without an identifiable pathogenic variant, and thereby inform guidelines for cascade screening for FH. |
| first_indexed | 2024-04-10T18:13:07Z |
| format | Article |
| id | doaj.art-e25a4284aba4472ea6b5be994414560b |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-04-10T18:13:07Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-e25a4284aba4472ea6b5be994414560b2023-02-02T10:31:36ZengMDPI AGJournal of Personalized Medicine2075-44262018-08-01832710.3390/jpm8030027jpm8030027Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) StudyIftikhar J. Kullo0Kent R. Bailey1Department of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN 55902, USADepartment of Health Sciences Research (KRB), Mayo Clinic, Rochester, MN 55902, USATo inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of LDLR, APOB, and PCSK9 and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score ≥ 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3–5, no pathogenic variant). We will enroll 50 patients with definite FH by recruiting an additional 26 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C > 155 mg/dL (>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case. The proposed clinical trial will compare the yield and cost of cascade screening for FH patients with/without an identifiable pathogenic variant, and thereby inform guidelines for cascade screening for FH.http://www.mdpi.com/2075-4426/8/3/27clinical trialdesignfamilial hypercholesterolemiacascade screeninggeneticsgenetic riskgenetic testingpersonalized medicine |
| spellingShingle | Iftikhar J. Kullo Kent R. Bailey Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study Journal of Personalized Medicine clinical trial design familial hypercholesterolemia cascade screening genetics genetic risk genetic testing personalized medicine |
| title | Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study |
| title_full | Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study |
| title_fullStr | Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study |
| title_full_unstemmed | Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study |
| title_short | Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study |
| title_sort | design of a controlled trial of cascade screening for hypercholesterolemia the cash study |
| topic | clinical trial design familial hypercholesterolemia cascade screening genetics genetic risk genetic testing personalized medicine |
| url | http://www.mdpi.com/2075-4426/8/3/27 |
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