Dominika Klimczak-Tomaniak, Karolina Andrzejczyk, Sabrina Abou Kamar, Sara Baart, Nick van Boven, K Martijn Akkerhuis, Alina Constantinescu, Kadir Caliskan, Suat Simsek, Tjeerd Germanse, Jan van Ramshorst, Jasper Brugts, Marek Kuch, Victor Umans, Eric Boersma, Isabella Kardys
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Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction.</p><p><strong>Methods: </strong>Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models.</p><p><strong>Results: </strong>Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP.</p><p><strong>Conclusions: </strong>Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. 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However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction.</p><p><strong>Methods: </strong>Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models.</p><p><strong>Results: </strong>Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). 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引用次数: 0
摘要
背景：肝功能异常会导致心力衰竭（HF）患者的临床预后恶化。然而，探讨慢性心力衰竭（CHF）患者肝功能参数的时间演变及其与临床预后的关系的研究却很少。本研究调查了射血分数降低的稳定型 CHF 患者的碱性磷酸酶（ALP）、γ 谷氨酰转肽酶（GGTP）、总胆红素（TBIL）和白蛋白（ALB）的详细时间模式及其与临床预后的关系：在 2.2（1.4-2.5）年的随访期间，每三个月收集 250 名患者的血浆样本。通过联合模型评估了重复测量的生物标志物水平与主要终点（PEP；心源性死亡、心脏移植、左心室辅助装置植入和因 HF 恶化住院的复合终点）之间的关系：平均年龄为 66 ± 13 岁，74% 为男性，25% 属于纽约心脏协会 III-IV 级。66名患者（26%）达到了PEP。重复测量的 TBIL、ALP、GGTP 和 ALB 水平与 PEP 相关，但需对 N-末端原 B 型钠尿肽和高敏肌钙蛋白 T 进行调整（生物标记物水平每增加一倍的危险比 [95% 置信区间]：1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 和 1.14 [1.09; 1.20], p < 0.001）。经临床变量调整后，ALP和GGTP的序列水平以及ALB和TBIL的时间变化斜率也与PEP显著相关：结论：TBIL、ALP、GGTP 和 ALB 血清水平的变化先于慢性阻塞性肺疾病患者不良心血管事件的发生。在临床实践中，这些常规肝功能参数可为射血分数降低的心力衰竭患者提供额外的预后信息。
Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).
Background: Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction.
Methods: Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models.
Results: Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP.
Conclusions: Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.
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