Blood Biomarkers Associated with Adverse Outcomes in Heart Failure

与心力衰竭不良后果相关的血液生物标志物

• 批准号: 10650694
• 负责人: Susan Hedayati
• 金额: $ 12.3万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2023-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10650694
• 关键词: Aldosterone Antagonists; Biological Markers; Blood; Blood Tests; Cardiovascular system; Cause of Death; Cessation of life; Chronic Kidney Failure; Clinical; Complex; Creatinine; Data; Data Set; Disease Progression; EFRAC; Eligibility Determination; Equation; Evaluation; Event; Functional disorder; Future; Galectin 3; Glomerular Filtration Rate; Goals; Heart; Heart Arrest; Heart Transplantation; Heart failure; Hospitalization; Kidney; Kidney Diseases; Knowledge; Left Ventricular Hypertrophy; Life; Measurable; Measurement; Measures; Mediating; Modeling; National Heart, Lung, and Blood Institute; Outcome; Participant; Pathogenesis; Pathway interactions; Patients; Population; Prognostic Marker; Registries; Renal function; Risk; Sample Size; Sampling; Serum; Side; Specimen; Testing; Tumorigenicity; adverse outcome; biomarker identification; clinical decision-making; clinical practice; cohort; conventional therapy; data registry; hazard; heart function; heart preservation; high risk; implantation; interest; left ventricular assist device; mortality; mortality risk; novel; post gamma-globulins; preservation; prognostication; programs; prospective; renal damage; sarcopenia; standard of care; study population; ventricular assist device

Project Abstract We aim to investigate which biomarkers are most useful in identifying increased risk for adverse cardiovascular (CV) and kidney outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and with reduced ejection fraction (HFrEF). This is imperative because chronic kidney disease (CKD) is common among patients with heart failure and associated with adverse outcomes. Up to 56% of patients with heart failure suffer from kidney function decline, subsequently leading to worse CV outcomes, but biomarkers to accurately identify which patients are at risk for decline in kidney glomerular filtration rate (GFR) are lacking. This not only limits prognostication, but makes clinical decisions regarding eligibility of patients with HFrEF for advanced therapies very challenging. Kidney disease can be assessed using GFR, which can be estimated using serum creatinine (eGFRcr), cystatin C (eGFRcys), or a weighted average of the two (eGFRcr-cys). It is unknown whether eGFRcr, eGFRcys, or eGFRcr-cys is better at predicting CV outcomes among patients with HFpEF or HFrEF. Additionally, soluble suppression of tumorogenicity 2 (ST2), and galectin-3 are easily obtainable blood biomarkers that may be associated with CKD progression and increased mortality, predominantly in patients with HFrEF, but have not been tested in patients with HFpEF. These biomarkers will be useful in understanding which patients are at increased risk of GFR decline and adverse CV events. Moreover, identifying such biomarkers will pave the way for future studies to better understand kidney disease pathogenesis in the setting of heart failure. To answer these questions, we plan to obtain specimens from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial (TOPCAT), a study population with HFpEF available in BioLINCC. Of 3445 participants, 220 have serum samples available at baseline and one year for analysis. We plan to measure serum cystatin C, ST2, and galectin-3. Our other biomarker of interest, serum creatinine, is already available in the dataset. We will use these data to: Aim 1a, test the association between baseline and increasing levels of serum ST2 and galectin-3 with the composite outcome of aborted cardiac arrest, heart failure hospitalization, or cardiovascular (CV) death; Aim 1b, test the association between baseline and increasing levels of serum ST2 and galectin-3 and the outcome of change in eGFRcr-cys from baseline to 1 year; Aim 2, investigate which GFR estimate is more predictive of the composite outcome; and Aim 3, analyze data from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life (REVIVAL), which is also publicly available in BioLINCC and has baseline serum creatinine and cystatin C measurements available, to evaluate which GFR estimate is the best predictor of all-cause mortality and a composite of heart failure hospitalization and CV death in patients with HFrEF. The overarching hypotheses are that (1) serum ST2 and galectin-3 are biomarkers associated with adverse CV and kidney outcomes in HFpEF patients; (2) eGFRcr-cys is the best GFR estimate to predict adverse outcomes in patients with HFpEF and HFrEF.

项目摘要 我们的目标是研究哪些生物标志物在识别心血管不良风险增加方面最有用 射血分数保留 (HFpEF) 的心力衰竭患者的 (CV) 和肾脏结局 射血分数降低（HFrEF）。这是当务之急，因为慢性肾病（CKD）在人群中很常见 患有心力衰竭并与不良后果相关的患者。高达 56% 的心力衰竭患者患有心力衰竭 肾功能下降，随后导致更糟糕的心血管结果，但生物标志物可以准确识别 哪些患者面临肾小球滤过率（GFR）下降的风险？这不仅限制了 预测，但针对 HFrEF 患者接受先进治疗的资格做出临床决策 非常具有挑战性。肾脏疾病可以使用 GFR 进行评估，GFR 可以使用血清肌酐进行评估 (eGFRcr)、半胱氨酸蛋白酶抑制剂 C (eGFRcys) 或两者的加权平均值 (eGFRcr-cys)。目前尚不清楚 eGFRcr、 eGFRcys 或 eGFRcr-cys 能够更好地预测 HFpEF 或 HFrEF 患者的心血管结局。此外， 可溶性致瘤性抑制 2 (ST2) 和半乳糖凝集素 3 是容易获得的血液生物标志物， 与 CKD 进展和死亡率增加相关，主要发生在 HFrEF 患者中，但 尚未在 HFpEF 患者中进行测试。这些生物标志物将有助于了解哪些患者 GFR 下降和不良心血管事件的风险增加。此外，识别此类生物标志物将 为未来的研究更好地了解心脏疾病中肾脏疾病的发病机制铺平道路 失败。为了回答这些问题，我们计划从保存心脏的治疗中获取标本 醛固酮拮抗剂功能性心力衰竭试验 (TOPCAT)，具有 HFpEF 的研究人群 在BioLINCC。在 3445 名参与者中，220 名拥有基线和一年的血清样本可供分析。我们 计划测量血清胱抑素 C、ST2 和半乳糖凝集素 3。我们感兴趣的另一个生物标志物血清肌酐是 数据集中已经可用。我们将使用这些数据来： 目标 1a，测试基线和 血清 ST2 和半乳糖凝集素 3 水平升高，导致心脏骤停、心力衰竭的复合结果 住院或心血管（CV）死亡；目标 1b，测试基线和增量之间的关联 血清 ST2 和半乳糖凝集素 3 水平以及 eGFRcr-cys 从基线到 1 年的变化结果；目标2， 研究哪种 GFR 估计值更能预测综合结果；目标 3，分析来自 流动生活心室辅助装置重要信息注册评估 (REVIVAL)， 也在 BioLINCC 中公开提供，并提供基线血清肌酐和胱抑素 C 测量值， 评估哪种 GFR 估计值是全因死亡率和心力衰竭综合死亡率的最佳预测因子 HFrEF 患者的住院和心血管死亡。总体假设是 (1) 血清 ST2 和 Galectin-3 是与 HFpEF 患者不良心血管和肾脏结局相关的生物标志物； (2) eGFRcr-cys 是预测 HFpEF 和 HFrEF 患者不良后果的最佳 GFR 估计值。