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 我们的目的是研究哪些生物标志物在识别不良心血管疾病风险增加方面最有用。 (CV)射血分数正常的心力衰竭（HFpEF）患者和 射血分数降低（HFrEF）。这是必要的，因为慢性肾脏病（CKD）是常见的， 心力衰竭患者并伴有不良结局。高达56%的心力衰竭患者 肾功能下降，随后导致CV结局恶化，但生物标志物可准确识别 哪些患者存在肾小球滤过率（GFR）下降的风险。这不仅限制了 论证，但做出关于HFrEF患者接受高级治疗资格的临床决策 非常有挑战性。肾脏疾病可以用GFR来评估，GFR可以用血清肌酐来估计 在一个实施方案中，细胞因子可以是生长因子受体（eGFRcr）、半胱氨酸蛋白酶抑制剂C（eGFRcys）或两者的加权平均值（eGFRcr-cys）。尚不清楚eGFRcr， eGFRcys或eGFRcr-cys在预测HFpEF或HFrEF患者的CV结局方面更好。此外，本发明还 可溶性肿瘤发生抑制2（ST 2）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 未在HFpEF患者中进行检测。这些生物标志物将有助于了解哪些患者 GFR下降和不良CV事件的风险增加。此外，识别这些生物标志物将 为未来的研究铺平道路，以更好地了解心脏环境中的肾脏疾病发病机制。 失败为了回答这些问题，我们计划从保存心脏的治疗中获得标本， 醛固酮拮抗剂试验（TOPCAT），一项HFpEF研究人群可用 在BioLINCC。在3445名参与者中，220名在基线和一年内可获得血清样本进行分析。我们 计划测量血清胱抑素C、ST 2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， 已经在数据集中。我们将使用这些数据：目标1a，测试基线和 血清ST 2和半乳糖凝集素-3水平升高，复合结局为心脏骤停流产、心力衰竭 住院或心血管（CV）死亡;目的1b，检验基线和增加的 血清ST 2和半乳糖凝集素-3的水平以及从基线到1年的eGFRcr-cys变化的结果;目的2， 研究哪种GFR估计值更能预测复合结局;目标3，分析来自 心室辅助装置在非卧床生活中的重要信息登记研究评价（REVIVAL）， 也可在BioLINCC中公开获得，并且具有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复合终点的最佳预测因子 HFrEF患者的住院和CV死亡。总体假设是（1）血清ST 2和 半乳糖凝集素-3是与HFpEF患者的不良CV和肾脏结局相关的生物标志物;（2）eGFRcr-cys 是预测HFpEF和HFrEF患者不良结局的最佳GFR估计值。