Entwistle Amy, Walker Susan, Knecht Anne, Strum Susan L, Shah Asad A, Pustavoitau Aliaksei, Mitin Natalia, Williams Judson B
Sapere Bio, Research Triangle Park, NC, USA.
Apex Biostatistics, Apex, NC, USA.
Cardiol Cardiovasc Med. 2024;8(3):267-274. doi: 10.26502/fccm.92920387. Epub 2024 Jun 26.
Improved pre-operative risk stratification methods are needed for targeted risk mitigation and optimization of care pathways for cardiac patients. This is the first report demonstrating pre-operative, aging-related biomarkers of cellular senescence and immune system function can predict risk of common and serious cardiac surgery-related adverse events.
Multi-center 331-patient cohort study that enrolled patients undergoing coronary artery bypass grafing (CABG) surgery with 30-day follow-up. Primary outcome was KDIGO-defined acute kidney injury (AKI). Secondary outcomes: decline in eGFR ≥25% at 30d and a composite of major adverse cardiac and kidney events at 30d (MACKE30). Biomarkers were assessed in blood samples collected prior to surgery.
A multivariate regression model of six senescence biomarkers (p16, p14, LAG3, CD244, CD28 and suPAR) identified patients at risk for AKI (NPV 86.6%, accuracy 78.6%), decline in eGFR (NPV 93.5%, accuracy 85.2%), and MACKE30 (NPV 91.4%, accuracy 79.9%). Patients in the top risk tertile had 7.8 (3.3-18.4) higher odds of developing AKI, 4.5 (1.6-12.6) higher odds of developing renal decline at 30d follow-up, and 5.7 (2.1-15.6) higher odds of developing MACKE30 versus patients in the bottom tertile. All models remained significant when adjusted for clinical variables.
A network of senescence biomarkers, a fundamental mechanism of aging, can identify patients at risk for adverse kidney and cardiac events when measured pre-operatively. These findings lay the foundation to improve pre-surgical risk assessment with measures that capture heterogeneity of aging, thereby improving clinical outcomes and resource utilization in cardiac surgery.
需要改进术前风险分层方法，以针对性地降低风险并优化心脏病人的护理路径。这是首份报告表明，术前与衰老相关的细胞衰老和免疫系统功能生物标志物可预测常见且严重的心脏手术相关不良事件的风险。
一项多中心、纳入331例患者的队列研究，这些患者接受冠状动脉旁路移植术（CABG）并进行30天随访。主要结局是KDIGO定义的急性肾损伤（AKI）。次要结局：术后30天估算肾小球滤过率（eGFR）下降≥25%，以及术后30天主要心脏和肾脏不良事件复合结局（MACKE30）。在术前采集的血样中评估生物标志物。
一个由六种衰老生物标志物（p16、p14、淋巴细胞活化基因3蛋白（LAG3）、2B4蛋白（CD244）、CD28和可溶性尿激酶型纤溶酶原激活物受体（suPAR））组成的多变量回归模型，识别出有AKI风险（阴性预测值86.6%，准确率78.6%）、eGFR下降风险（阴性预测值93.5%，准确率85.2%）和MACKE30风险（阴性预测值91.4%，准确率79.9%）的患者。处于最高风险三分位数的患者发生AKI的几率比处于最低三分位数的患者高7.8（3.3 - 18.4）倍，在30天随访时发生肾功能下降的几率高4.5（1.6 - 12.6）倍，发生MACKE30的几率高5.7（2.1 - 15.6）倍。在对临床变量进行调整后，所有模型仍然具有显著性。
衰老生物标志物网络作为衰老的基本机制，在术前测量时可识别出有肾脏和心脏不良事件风险的患者。这些发现为通过捕捉衰老异质性的措施改进术前风险评估奠定了基础，从而改善心脏手术的临床结局和资源利用。
