Damon A Bell1, Jing Pang2, Sally Burrows2, Timothy R Bates3, Frank M van Bockxmeer4, Amanda J Hooper5, Peter O'Leary6, John R Burnett1, Gerald F Watts7. 1. Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia. 2. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. 3. Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. 4. Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia; School of Surgery, University of Western Australia, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia. 5. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia. 6. Faculty of Health Sciences, Curtin University, Perth, Australia; School of Women's and Infants' Health, University of Western Australia, Perth, Australia; PathWest Laboratory Medicine WA, Perth, Australia. 7. Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.
Abstract
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.
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.
Authors: Pãmela Rodrigues de Souza Silva; Cinthia Elim Jannes; Theo G M Oliveira; Luz Marina Gómez Gómez; José E Krieger; Raul D Santos; Alexandre Costa Pereira Journal: Arq Bras Cardiol Date: 2018-08-23 Impact factor: 2.000
Authors: Alison Luk Young; Phyllis N Butow; Katherine M Tucker; Claire E Wakefield; Emma Healey; Rachel Williams Journal: BMJ Open Date: 2020-02-25 Impact factor: 2.692