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A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia: enhancing the precision of risk assessment |
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| Authors: | Katrina L. Ellis Amanda J. Hooper Jing Pang Dick C. Chan John R. Burnett Damon A. Bell Carl J. Schultz Eric K. Moses Gerald F. Watts |
| Affiliation: | 1. Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia;2. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia;3. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia;4. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia;5. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia;6. Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia |
| Abstract: | Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD); however, risk prediction and stratification remain a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk. The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation-positive (n = 251) and mutation-negative (n = 560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics, and CAD were assessed using regression analyses. The average age of patients was 49.6 years, and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation-positive [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.3-8.2; P = .009] and mutation-negative FH patients (OR = 1.8; 95% CI = 1.0-3.3; P = .039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (P = .039). A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid-lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic. |
| Keywords: | atherosclerosis coronary artery disease familial hypercholesterolaemia genetic risk score |