Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older

被引:18
|
作者
Neumann, Johannes T. [1 ,2 ,3 ]
Riaz, Moeen [1 ]
Bakshi, Andrew [1 ]
Polekhina, Galina [1 ]
Thao, Le T. P. [1 ]
Nelson, Mark R. [1 ,4 ]
Woods, Robyn L. [1 ]
Abraham, Gad [5 ]
Inouye, Michael [5 ,6 ]
Reid, Christopher M. [1 ,7 ]
Tonkin, Andrew M. [1 ]
McNeil, John [1 ]
Lacaze, Paul [1 ]
机构
[1] Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia
[2] Univ Heart & Vasc Ctr, Dept Cardiol, Hamburg, Germany
[3] German Ctr Cardiovasc Res DZHK, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany
[4] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia
[5] Baker Heart & Diabet Inst, Cambridge Baker Syst Genom Initiat, Melbourne, Vic, Australia
[6] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England
[7] Curtin Univ, Sch Publ Hlth, Perth, WA, Australia
来源
CIRCULATION-GENOMIC AND PRECISION MEDICINE | 2022年 / 15卷 / 01期
基金
英国医学研究理事会; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会;
关键词
aspirin; cardiovascular disease; genetics; prognosis; risk factor; CARDIOVASCULAR-DISEASE; PREDICTIVE ACCURACY; ADULTS;
D O I
10.1161/CIRCGEN.121.003429
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 ASPR EE 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.
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页数:7
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