Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course.

IF 6 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Genomic and Precision Medicine Pub Date : 2025-02-01 Epub Date: 2025-01-24 DOI:10.1161/CIRCGEN.124.004681

Sarah M Urbut, So Mi Jemma Cho, Kaavya Paruchuri, Buu Truong, Sara Haidermota, Gina M Peloso, Whitney E Hornsby, Anthony Philippakis, Akl C Fahed, Pradeep Natarajan

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引用次数: 0

Abstract

Background: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.

Methods: A longitudinal study was performed using data from 2 cohort studies: the FOS (Framingham Offspring Study) with 3588 participants aged 19 to 57 years and the UKB (UK Biobank) with 327 837 participants aged 40 years to 70 years. A total of 134 765 and 3 831 734 person-time years were observed in FOS and UKB, respectively. Hazard ratios for CAD were calculated for polygenic risk score (PRS) and clinical risk factors at each age of enrollment. The relative importance of PRS and pooled cohort equations in predicting CAD events was also evaluated by age groups.

Results: The importance of CAD PRS diminished over the life course, with a hazard ratio of 3.58 (95% CI, 1.39-9.19) at the age of 19 years in FOS and a hazard ratio of 1.51 (95% CI, 1.48-1.54) by the age of 70 years in UKB. Clinical risk factors exhibited similar age-dependent trends. PRS significantly outperformed pooled cohort equations in identifying subsequent CAD events in the 40- to 45-year age group, with 3.2-fold more appropriately identified events. Overall, adding PRS improved the area under the receiving operating curve of the pooled cohort equations by an average of +5.1% (95% CI, 4.9%-5.2%) across all age groups; among individuals <55 years, PRS augmented the area under the receiver operater curve (ROC) of the pooled cohort equations by 6.5% (95% CI, 5.5%-7.5%; P<0.001).

Conclusions: Genomic and clinical risk factors for CAD display time-varying importance across the lifespan. The study underscores the added value of CAD PRS, particularly among individuals younger than 55 years, for enhancing early risk prediction and prevention strategies. All results are available at https://surbut.github.io/dynamicHRpaper/index.html.

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冠状动脉疾病的基因组和临床风险在生命过程中的动态重要性。

背景：早期识别高冠状动脉疾病（CAD）风险个体可能有助于更有效的预防策略。然而，现有的10年风险框架在早期识别方面是无效的。我们试图了解基因组和临床因素在生命阶段的可变重要性如何显著改善终身CAD事件预测。方法：采用两项队列研究的数据进行纵向研究：FOS （Framingham Offspring study）有3588名参与者，年龄在19至57岁之间；UKB （UK Biobank）有327837名参与者，年龄在40至70岁之间。FOS和UKB分别有134 765和3 831 734人次年。在每个入组年龄，计算冠心病的多基因风险评分（PRS）和临床危险因素的风险比。PRS和合并队列方程在预测CAD事件中的相对重要性也按年龄组进行了评估。结果：CAD PRS的重要性在生命过程中逐渐降低，FOS患者19岁时的风险比为3.58 (95% CI, 1.39-9.19)， UKB患者70岁时的风险比为1.51 （95% CI, 1.48-1.54）。临床危险因素表现出类似的年龄依赖趋势。在识别40至45岁年龄组的后续CAD事件方面，PRS显著优于合并队列方程，其识别事件的准确性高出3.2倍。总体而言，在所有年龄组中，添加PRS使合并队列方程的接收操作曲线下的面积平均提高了+5.1% (95% CI, 4.9%-5.2%)；结论：CAD的基因组和临床危险因素在整个生命周期中表现出随时间变化的重要性。该研究强调了CAD PRS的附加价值，特别是在55岁以下的个体中，可以增强早期风险预测和预防策略。所有结果可在https://surbut.github.io/dynamicHRpaper/index.html上获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

9.20

自引率

5.40%

发文量

144

期刊介绍： Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.