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 我们旨在调查哪些生物标志物在确定不良心血管的风险增加最有用 （CV）和肾脏结局的心力衰竭患者，并保留了射血分数（HFPEF），并带有 减少射血分数（HFREF）。这是必须的，因为慢性肾脏疾病（CKD）很常见 心力衰竭并与不良预后有关的患者。多达56％的心力衰竭患者 由于肾功能下降，随后导致CV结果较差，但生物标志物可以准确识别 缺乏肾脏肾小球滤过率（GFR）下降的患者。这不仅限制 预测，但就HFREF患者的资格做出晚期疗法做出临床决定 非常具有挑战性。可以使用GFR评估肾脏疾病，可以使用血清肌酐估算 （EGFRCR），半胱氨酸蛋白酶C（EGFRCYS）或两个（EGFRCR-cys）的加权平均值。尚不清楚egfrcr是否 EGFRCYS或EGFRCR-CYS可以更好地预测HFPEF或HFREF患者的CV结局。此外， 可溶性抑制肿瘤性2（ST2）和Galectin-3是可以轻松获得的血液生物标志物 与CKD进展和死亡率增加有关，主要是HFREF患者，但具有 未在HFPEF患者中测试。这些生物标志物将有助于了解哪些患者 GFR下降和不良简历事件的风险增加。此外，识别这样的生物标志物将会 为将来的研究铺平道路，以更好地理解心脏的肾脏疾病发病机理 失败。要回答这些问题，我们计划从保存心脏的处理中获得标本 醛固酮拮抗剂试验（TOPCAT）功能心力衰竭，这是一个可用的HFPEF的研究人群 在Biolincc中。在3445名参与者中，有220名有血清样品可在基线和一年进行分析。我们 计划测量血清胱抑素C，ST2和lectectin-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：AIM 1A，测试基线和基线之间的关联 血清ST2和Galectin-3水平增加，心脏衰竭的复合结果 住院或心血管（CV）死亡；目标1B，测试基线与增加之间的关联 血清ST2和Galectin-3的水平以及从基线到1年的EGFRCR-CYS变化的结果；目标2， 研究哪些GFR估计值更可预测复合结果；和AIM 3，分析数据 注册表评估室内室内辅助设备的重要信息（复兴），这是 也可以在Biolincc公开使用，并具有基线血清肌酐和胱抑素C的测量值 评估哪个GFR估计是全因死亡率的最佳预测指标和心力衰竭的综合 HFREF患者的住院和简历死亡。总体假设是（1）血清ST2和 Galectin-3是HFPEF患者中与不良CV和肾脏结局相关的生物标志物； （2）egfrcr-cys 是预测HFPEF和HFREF患者不良结果的最佳GFR估计值。