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Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting
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| Zeitschriftentitel: | Circulation |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , |
| In: | Circulation, 135, 2017, 22, S. 2091-2101 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar |
|---|---|
| author |
Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar |
| spellingShingle |
Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar Circulation Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting Physiology (medical) Cardiology and Cardiovascular Medicine |
| author_sort |
natarajan, pradeep |
| spelling |
Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circulationaha.116.024436 <jats:sec> <jats:title>Background:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22–60; <jats:italic>P</jats:italic> <0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8–37; <jats:italic>P</jats:italic> =0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others ( <jats:italic>P</jats:italic> for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0–5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6–1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04–1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2–17.8) burden of carotid plaque. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. </jats:p> </jats:sec> Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting Circulation |
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10.1161/circulationaha.116.024436 |
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Circulation |
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| title |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_unstemmed |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_full |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_fullStr |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_full_unstemmed |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_short |
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_sort |
polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting |
| topic |
Physiology (medical) Cardiology and Cardiovascular Medicine |
| url |
http://dx.doi.org/10.1161/circulationaha.116.024436 |
| publishDate |
2017 |
| physical |
2091-2101 |
| description |
<jats:sec>
<jats:title>Background:</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>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).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>
Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22–60;
<jats:italic>P</jats:italic>
<0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8–37;
<jats:italic>P</jats:italic>
=0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others (
<jats:italic>P</jats:italic>
for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0–5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6–1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04–1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2–17.8) burden of carotid plaque.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration:</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link>
. Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration.
</jats:p>
</jats:sec> |
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| author | Natarajan, Pradeep, Young, Robin, Stitziel, Nathan O., Padmanabhan, Sandosh, Baber, Usman, Mehran, Roxana, Sartori, Samantha, Fuster, Valentin, Reilly, Dermot F., Butterworth, Adam, Rader, Daniel J., Ford, Ian, Sattar, Naveed, Kathiresan, Sekar |
| author_facet | Natarajan, Pradeep, Young, Robin, Stitziel, Nathan O., Padmanabhan, Sandosh, Baber, Usman, Mehran, Roxana, Sartori, Samantha, Fuster, Valentin, Reilly, Dermot F., Butterworth, Adam, Rader, Daniel J., Ford, Ian, Sattar, Naveed, Kathiresan, Sekar, Natarajan, Pradeep, Young, Robin, Stitziel, Nathan O., Padmanabhan, Sandosh, Baber, Usman, Mehran, Roxana, Sartori, Samantha, Fuster, Valentin, Reilly, Dermot F., Butterworth, Adam, Rader, Daniel J., Ford, Ian, Sattar, Naveed, Kathiresan, Sekar |
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| description | <jats:sec> <jats:title>Background:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22–60; <jats:italic>P</jats:italic> <0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8–37; <jats:italic>P</jats:italic> =0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others ( <jats:italic>P</jats:italic> for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0–5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6–1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04–1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2–17.8) burden of carotid plaque. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. </jats:p> </jats:sec> |
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| spelling | Natarajan, Pradeep Young, Robin Stitziel, Nathan O. Padmanabhan, Sandosh Baber, Usman Mehran, Roxana Sartori, Samantha Fuster, Valentin Reilly, Dermot F. Butterworth, Adam Rader, Daniel J. Ford, Ian Sattar, Naveed Kathiresan, Sekar 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circulationaha.116.024436 <jats:sec> <jats:title>Background:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22–60; <jats:italic>P</jats:italic> <0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8–37; <jats:italic>P</jats:italic> =0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others ( <jats:italic>P</jats:italic> for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0–5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6–1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04–1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2–17.8) burden of carotid plaque. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. </jats:p> </jats:sec> Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting Circulation |
| spellingShingle | Natarajan, Pradeep, Young, Robin, Stitziel, Nathan O., Padmanabhan, Sandosh, Baber, Usman, Mehran, Roxana, Sartori, Samantha, Fuster, Valentin, Reilly, Dermot F., Butterworth, Adam, Rader, Daniel J., Ford, Ian, Sattar, Naveed, Kathiresan, Sekar, Circulation, Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting, Physiology (medical), Cardiology and Cardiovascular Medicine |
| title | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_full | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_fullStr | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_full_unstemmed | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_short | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| title_sort | polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting |
| title_unstemmed | Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting |
| topic | Physiology (medical), Cardiology and Cardiovascular Medicine |
| url | http://dx.doi.org/10.1161/circulationaha.116.024436 |