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<p>Risk factors and subclinical pathophysiology of coronary artery disease (CAD) begin in childhood, yet identifying candidates for primordial prevention remains challenging. Polygenic risk scores (PRS) provide a DNA-based risk marker from birth that can stratify children by lifetime CAD risk. We evaluated the potential clinical utility and cost-effectiveness of PRS-guided CAD prevention in children using health economic modeling. A Markov model compared PRS-guided prevention with standard prevention in a hypothetical group of 10,000 children. Children in the top 20% of PRS (<i>n</i> = 2000) were assumed to receive behavioral interventions. Assuming a 10-year CAD incidence of 12% during adulthood among those in the top 20% of the PRS distribution and a conservative 30% relative risk reduction with preventive intervention, PRS-guided prevention was projected to prevent 72 CAD events among 2000 high-risk children (3.6% absolute event reduction), yielding a return on investment of 3614%. PRS enables early, targeted prevention, improving outcomes, and lowering lifetime costs.</p>

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Economic modeling of polygenic risk prediction of coronary artery disease in childhood

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月23日

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  • Fouad Bitar,
  • Rana Zareef,
  • Hussain Ismaeel,
  • Roukoz Abou-Karam,
  • Mariam Arabi,
  • Ziad Bulbul,
  • Fadi F. Bitar,
  • Akl C. Fahed

摘要

Risk factors and subclinical pathophysiology of coronary artery disease (CAD) begin in childhood, yet identifying candidates for primordial prevention remains challenging. Polygenic risk scores (PRS) provide a DNA-based risk marker from birth that can stratify children by lifetime CAD risk. We evaluated the potential clinical utility and cost-effectiveness of PRS-guided CAD prevention in children using health economic modeling. A Markov model compared PRS-guided prevention with standard prevention in a hypothetical group of 10,000 children. Children in the top 20% of PRS (n = 2000) were assumed to receive behavioral interventions. Assuming a 10-year CAD incidence of 12% during adulthood among those in the top 20% of the PRS distribution and a conservative 30% relative risk reduction with preventive intervention, PRS-guided prevention was projected to prevent 72 CAD events among 2000 high-risk children (3.6% absolute event reduction), yielding a return on investment of 3614%. PRS enables early, targeted prevention, improving outcomes, and lowering lifetime costs.