在慢性病中发生心力衰竭:蛋白质组学为生物学和风险分层提供了信息
Ruth F Dubin1, Rajat Deo2, Yue Ren3
1Division of Nephrology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, H5.122E, Dallas, TX 75390, USA.
European heart journal
|May 17, 2024
概括
在慢性病 (CKD) 中心力衰竭 (HF) 是常见的. 大规模蛋白质组学确定了新型蛋白质生物标记物和可药物标,改善了风险预测模型的现有得分.
科学领域:
- 生物标志物和蛋白质组学
- 心血管疾病是什么心血管疾病
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 心力衰竭 (HF) 是慢性病 (CKD) 患者的一个重要并发症.
- 现有的风险预测模型,如预防心力衰竭 (PCP-HF) 的聚合队列方程,在CKD人群中表现不佳.
- 对于新的治疗标和改善CKD中HF风险分层的需求至关重要.
研究的目的:
- 确定与慢性病 (CKD) 患者发生心力衰竭 (HF) 相关的新型循环蛋白生物标志物.
- 使用蛋白质组数据,探索CKD中HF的潜在因果关系和可用药物的标.
- 开发和验证用于CKD中HF预测的增强型多蛋白风险模型,将其性能与既定得分进行比较.
主要方法:
- 在2906名从慢性功能衰竭队列 (CRIC) 研究的参与者中,SomaScan对4638种蛋白质进行蛋白质组分析,在社区动脉样硬化风险 (ARIC) 研究中得到验证.
- 主要结局:14年的事件高频率. 二次结局:四年HF,HF减少喷射分数,和HF保留喷射分数.
- 门德尔随机化和基因本体学的应用用于因果关系评估,并将新型多蛋白模型与PCP-HF风险评分进行比较.
主要成果:
- 超过200种蛋白质最初与CKD患者发生的HF有关 (P < 1 × 10-5) 经过对估计的淋巴透率进行调整后.
- 在对共变量进行调整后,包括N-终端亲B型性尿素,17种蛋白质仍然与高频率有显著的关联.
- 通过孟德尔的随机化确定了四个可药物治疗的蛋白质标 (FCG2B,IGFBP3,CAH6,ASGR1).
- 一个48蛋白模型显示出优异的预测性能 (CRIC中的C-统计值为0.790),与PCP-HF模型 (C-统计值为0.703) 相比,对于发生的HF.
结论:
- 大规模蛋白质组学已经成功地确定了新型循环蛋白生物标志物和CKD背景下HF的潜在媒介.
- 与现有的PCP-HF风险评分相比,开发的蛋白质组风险模型为预测CKD患者的HF提供了更好的准确性.
- 这些发现突出了开发新预防疗法的有希望途径,并完善了对HF在CKD中的风险分层策略.
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