Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting
Broad Institute · Merck & Co., Inc., Rahway, NJ, USA (United States) · +11 more institutions
Abstract
Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis.
We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage).
Citation impact
- FWCI
- 44.37
- Percentile
- 100%
- References
- 44
Authors
14- PNPradeep NatarajanCorresponding
Broad Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Harvard University, Cardiovascular Institute of the South, Edinburgh Cancer Research, British Heart Foundation, Massachusetts General Hospital, Center for Human Genetics, Translational Therapeutics (United States), Massachusetts Institute of Technology, University of Glasgow, University of Pennsylvania, Icahn School of Medicine at Mount Sinai
- RYRobin Young
Broad Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Harvard University, Cardiovascular Institute of the South, Edinburgh Cancer Research, British Heart Foundation, Massachusetts General Hospital, Center for Human Genetics, Translational Therapeutics (United States), Massachusetts Institute of Technology, University of Glasgow, University of Pennsylvania, Icahn School of Medicine at Mount Sinai
- NONathan O. Stitziel
Broad Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Harvard University, Cardiovascular Institute of the South, Edinburgh Cancer Research, British Heart Foundation, Massachusetts General Hospital, Center for Human Genetics, Translational Therapeutics (United States), Massachusetts Institute of Technology, University of Glasgow, University of Pennsylvania, Icahn School of Medicine at Mount Sinai
- SPSandosh Padmanabhan
Broad Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Harvard University, Cardiovascular Institute of the South, Edinburgh Cancer Research, British Heart Foundation, Massachusetts General Hospital, Center for Human Genetics, Translational Therapeutics (United States), Massachusetts Institute of Technology, University of Glasgow, University of Pennsylvania, Icahn School of Medicine at Mount Sinai
- UBUsman Baber
Broad Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Harvard University, Cardiovascular Institute of the South, Edinburgh Cancer Research, British Heart Foundation, Massachusetts General Hospital, Center for Human Genetics, Translational Therapeutics (United States), Massachusetts Institute of Technology, University of Glasgow, University of Pennsylvania, Icahn School of Medicine at Mount Sinai
Topics & keywords
- Medicine
- Primary prevention
- Statin
- Internal medicine
- Subgroup analysis
- Atherosclerotic cardiovascular disease
- Relative risk
- Polygenic risk score
- Good health and well-being