Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience
Background: Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL-cholesterol and premature coronary artery disease (CAD). Several guidelines recommend genetic cascade screening relatives of probands (index cases)...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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2015
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| Online Access: | http://hdl.handle.net/20.500.11937/47742 |
| _version_ | 1848757917924196352 |
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| author | Bell, D. Pang, J. Burrows, S. Bates, T. van Bockxmeer, F. Hooper, A. O'Leary, Peter Burnett, J. Watts, G. |
| author_facet | Bell, D. Pang, J. Burrows, S. Bates, T. van Bockxmeer, F. Hooper, A. O'Leary, Peter Burnett, J. Watts, G. |
| author_sort | Bell, D. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL-cholesterol and premature coronary artery disease (CAD). Several guidelines recommend genetic cascade screening relatives of probands (index cases) with genetically proven FH, but experience in a clinical service setting is limited. Methods: Relatives from 100 index cases with genetically confirmed FH underwent genetic and lipid testing via a centralised screening program in Western Australia. The program's effectiveness was evaluated as the number of newly diagnosed relatives with FH per index case and the proportional reduction in LDL-cholesterol after treatment. Results: Of 366 relatives tested for FH, 188 (51.4%) were found to have a pathogenic mutation. On average, 2 cases were detected per index case. Affected relatives were younger and less likely to have physical stigmata of FH and premature CAD than index cases (p<0.001). Of the new cases, 12.8% had hypertension, 2.7% had diabetes and 16.0% were smokers; 48.4% were already on statin therapy and these were older (p<0.001) and had more vascular risk factors and CAD (p<0.01) than those not on therapy. Significant reductions in LDL-cholesterol (-24.3%, p<0.001) were achieved overall, with previously untreated new cases of FH attaining a maximal average reduction of 42.5% in LDL-cholesterol after drug therapy. Over 90% of subjects were satisfied with screening and care. Conclusion: Genetic cascade screening co-ordinated by a centralised service is an effective and acceptable strategy for detecting FH in an Australian setting. A significant proportion of new cases exhibit other CAD risk factors and are already on statins, but have not received a prior diagnosis of FH. © 2014 Elsevier Ireland Ltd. |
| first_indexed | 2025-11-14T09:35:43Z |
| format | Journal Article |
| id | curtin-20.500.11937-47742 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:35:43Z |
| publishDate | 2015 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-477422017-09-13T14:18:23Z Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience Bell, D. Pang, J. Burrows, S. Bates, T. van Bockxmeer, F. Hooper, A. O'Leary, Peter Burnett, J. Watts, G. Background: Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL-cholesterol and premature coronary artery disease (CAD). Several guidelines recommend genetic cascade screening relatives of probands (index cases) with genetically proven FH, but experience in a clinical service setting is limited. Methods: Relatives from 100 index cases with genetically confirmed FH underwent genetic and lipid testing via a centralised screening program in Western Australia. The program's effectiveness was evaluated as the number of newly diagnosed relatives with FH per index case and the proportional reduction in LDL-cholesterol after treatment. Results: Of 366 relatives tested for FH, 188 (51.4%) were found to have a pathogenic mutation. On average, 2 cases were detected per index case. Affected relatives were younger and less likely to have physical stigmata of FH and premature CAD than index cases (p<0.001). Of the new cases, 12.8% had hypertension, 2.7% had diabetes and 16.0% were smokers; 48.4% were already on statin therapy and these were older (p<0.001) and had more vascular risk factors and CAD (p<0.01) than those not on therapy. Significant reductions in LDL-cholesterol (-24.3%, p<0.001) were achieved overall, with previously untreated new cases of FH attaining a maximal average reduction of 42.5% in LDL-cholesterol after drug therapy. Over 90% of subjects were satisfied with screening and care. Conclusion: Genetic cascade screening co-ordinated by a centralised service is an effective and acceptable strategy for detecting FH in an Australian setting. A significant proportion of new cases exhibit other CAD risk factors and are already on statins, but have not received a prior diagnosis of FH. © 2014 Elsevier Ireland Ltd. 2015 Journal Article http://hdl.handle.net/20.500.11937/47742 10.1016/j.atherosclerosis.2014.12.036 restricted |
| spellingShingle | Bell, D. Pang, J. Burrows, S. Bates, T. van Bockxmeer, F. Hooper, A. O'Leary, Peter Burnett, J. Watts, G. Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title | Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title_full | Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title_fullStr | Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title_full_unstemmed | Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title_short | Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience |
| title_sort | effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: an australian experience |
| url | http://hdl.handle.net/20.500.11937/47742 |