BACKGROUND Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. RESULTS This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. CONCLUSIONS The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.

中文翻译：

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PCSK9-LDL 受体轴和心力衰竭的结果

背景前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 结合低密度脂蛋白受体 (LDLR)，阻止其再循环。PCSK9 是动脉粥样硬化进展的风险预测因子和生物靶点。目的 本研究的目的是确定 PCSK9-LDLR 轴是否可以预测心力衰竭 (HF) 患者的风险。方法 BIOSTAT-CHF（慢性心力衰竭定制治疗的生物学研究）是一项多中心、跨国、前瞻性、观察性研究，纳入了心衰体征和/或症状恶化的患者。主要终点是全因死亡率和死亡率或因 HF 计划外住院的复合终点。我们实施了 Cox 比例风险回归来确定 PCSK9 和 LDLR 在添加到先前验证的 BIOSTAT-CHF 风险评分中时对这两种结果的同时调整的影响。结果 该研究包括 2,174 名患者（平均年龄：68 ± 12 岁；53.2% 有缺血性心脏病史）。中位数（四分位距）PCSK9 和 LDLR 水平分别为 1.81 U/ml（1.45 至 2.18）和 2.98 U/ml（2.45 至 3.53）。在随访期间，确定了 569 例死亡 (26.2%) 和 896 例 (41.2%) 复合终点。包括 BIOSTAT-CHF 风险评分、LDLR 和他汀类药物治疗作为协变量的多变量分析显示 PCSK9 水平与死亡风险之间呈正线性关联（风险比 [HR]：1.24；95% 置信区间 [CI]： 1.04 至 1.49；p = 0.020）和复合终点（HR：1.21；95% CI：1。05 至 1.40；p = 0.010）。对 LDLR 的类似分析显示，与死亡率（HR：0.86；95% CI：0.76 至 0.98；p = 0.025）和复合终点（HR：0.92；95% CI：0.83 至 1.01；p = 0.087）呈负相关。包括 PCSK9 和 LDLR 提高了风险评分性能。结论 PCSK9-LDLR 轴与 HF 患者的结局相关。未来的研究必须评估 PCSK9 抑制是否会导致 HF 更好的结果。