Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.
Department of Community Cardiovascular Medicine Fukushima Medical University Fukushima Japan.
J Am Heart Assoc. 2024 Sep 3;13(17):e035139. doi: 10.1161/JAHA.124.035139. Epub 2024 Aug 27.
Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver-synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin-A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin-A in connecting cardiac-hepatic-peripheral interaction.
We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin-A by ELISA. Correlation analysis revealed a negative association between fetuin-A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin-A levels. During a median follow-up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high-risk subgroup with lower fetuin-A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan-Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin-A and exercise intolerance was independently associated with increased risks of cardiac events.
Reduced circulating fetuin-A levels were associated with exercise intolerance in heart failure patients. Fetuin-A could emerge as a target implicated in exercise capacity connecting cardiac-hepatic-peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.
心力衰竭导致运动不耐受的原因是多因素病理生理机制。肝细胞因子是肝脏合成的分子，可调节外周组织的全身代谢。我们之前发现肝细胞因子胎球蛋白 A 与心力衰竭时的肝脏低灌注有关。在这里，我们研究了胎球蛋白 A 在连接心脏-肝脏-外周相互作用中的作用。
我们进行了一项前瞻性研究，纳入了 202 例连续住院的心力衰竭患者（平均年龄 56.8 岁；76.2%为男性），并进行了心肺运动测试。我们通过 ELISA 测量了胎球蛋白 A 的血清浓度。相关性分析显示，胎球蛋白 A 水平与最小分钟通气量与二氧化碳产生量之比、其斜率呈负相关，与峰值摄氧量呈正相关趋势。运动耐量受损的患者胎球蛋白 A 水平较低。在中位数为 1045 天的随访期间，18.3%的患者发生了心脏事件，包括 4 例心脏死亡和 33 例心力衰竭恶化。分类和回归树分析确定了一个高危亚组，其胎球蛋白 A 较低（<24.3mg/L）和运动耐量受损（峰值摄氧量<14.2ml/kg/min）。Kaplan-Meier 分析显示，该亚组发生心脏事件的风险最高。在多变量 Cox 比例风险模型中，低胎球蛋白 A 和运动不耐受的组合与心脏事件风险的增加独立相关。
心力衰竭患者循环胎球蛋白 A 水平降低与运动不耐受有关。胎球蛋白 A 可能成为连接心脏-肝脏-外周相互作用的运动能力的靶点，并作为预测预后的有价值的生物标志物，与峰值摄氧量结合使用。
