Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older
Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Language: | English |
| Published: |
LIPPINCOTT WILLIAMS & WILKINS
2022
|
| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/nhmrc/1136372 http://hdl.handle.net/20.500.11937/93095 |
| _version_ | 1848765696126746624 |
|---|---|
| author | Neumann, J.T. Riaz, M. Bakshi, A. Polekhina, G. Thao, L.T.P. Nelson, M.R. Woods, R.L. Abraham, G. Inouye, M. Reid, Christopher Tonkin, A.M. McNeil, J. Lacaze, P. |
| author_facet | Neumann, J.T. Riaz, M. Bakshi, A. Polekhina, G. Thao, L.T.P. Nelson, M.R. Woods, R.L. Abraham, G. Inouye, M. Reid, Christopher Tonkin, A.M. McNeil, J. Lacaze, P. |
| author_sort | Neumann, J.T. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. Methods: We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28). Conclusion: A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583. |
| first_indexed | 2025-11-14T11:39:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-93095 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:39:21Z |
| publishDate | 2022 |
| publisher | LIPPINCOTT WILLIAMS & WILKINS |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-930952023-09-06T07:21:11Z Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older Neumann, J.T. Riaz, M. Bakshi, A. Polekhina, G. Thao, L.T.P. Nelson, M.R. Woods, R.L. Abraham, G. Inouye, M. Reid, Christopher Tonkin, A.M. McNeil, J. Lacaze, P. Science & Technology Life Sciences & Biomedicine Cardiac & Cardiovascular Systems Genetics & Heredity Cardiovascular System & Cardiology aspirin cardiovascular disease genetics prognosis risk factor CARDIOVASCULAR-DISEASE PREDICTIVE ACCURACY ADULTS aspirin cardiovascular disease genetics prognosis risk factor Adult Aged Aged, 80 and over Aspirin Coronary Disease Female Humans Male Prognosis Prospective Studies Risk Factors Humans Coronary Disease Aspirin Prognosis Risk Factors Prospective Studies Adult Aged Aged, 80 and over Female Male Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. Methods: We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28). Conclusion: A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583. 2022 Journal Article http://hdl.handle.net/20.500.11937/93095 10.1161/CIRCGEN.121.003429 English http://purl.org/au-research/grants/nhmrc/1136372 http://creativecommons.org/licenses/by-nc/4.0/ LIPPINCOTT WILLIAMS & WILKINS fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Cardiac & Cardiovascular Systems Genetics & Heredity Cardiovascular System & Cardiology aspirin cardiovascular disease genetics prognosis risk factor CARDIOVASCULAR-DISEASE PREDICTIVE ACCURACY ADULTS aspirin cardiovascular disease genetics prognosis risk factor Adult Aged Aged, 80 and over Aspirin Coronary Disease Female Humans Male Prognosis Prospective Studies Risk Factors Humans Coronary Disease Aspirin Prognosis Risk Factors Prospective Studies Adult Aged Aged, 80 and over Female Male Neumann, J.T. Riaz, M. Bakshi, A. Polekhina, G. Thao, L.T.P. Nelson, M.R. Woods, R.L. Abraham, G. Inouye, M. Reid, Christopher Tonkin, A.M. McNeil, J. Lacaze, P. Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title | Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title_full | Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title_fullStr | Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title_full_unstemmed | Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title_short | Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older |
| title_sort | prognostic value of a polygenic risk score for coronary heart disease in individuals aged 70 years and older |
| topic | Science & Technology Life Sciences & Biomedicine Cardiac & Cardiovascular Systems Genetics & Heredity Cardiovascular System & Cardiology aspirin cardiovascular disease genetics prognosis risk factor CARDIOVASCULAR-DISEASE PREDICTIVE ACCURACY ADULTS aspirin cardiovascular disease genetics prognosis risk factor Adult Aged Aged, 80 and over Aspirin Coronary Disease Female Humans Male Prognosis Prospective Studies Risk Factors Humans Coronary Disease Aspirin Prognosis Risk Factors Prospective Studies Adult Aged Aged, 80 and over Female Male |
| url | http://purl.org/au-research/grants/nhmrc/1136372 http://hdl.handle.net/20.500.11937/93095 |