Division of Cardiovascular Disease and Comprehensive Cardiovascular Center, Department of Internal Medicine, University of Alabama at Birmingham, USA.
Division of Molecular Imaging and Therapeutics, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA.
ESC Heart Fail. 2020 Aug;7(4):1676-1687. doi: 10.1002/ehf2.12724. Epub 2020 May 18.
Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored.
The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P < 0.05).
Leucocyte count >7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.
先前的证据表明，白细胞增多与多种心血管疾病有关，包括射血分数降低的心力衰竭（HF rEF）。然而，白细胞计数在射血分数保留的心力衰竭（HFpEF）中的预后意义在很大程度上仍未得到探索。
使用治疗保留心功能的心力衰竭伴醛固酮拮抗剂的美洲队列（TOPCAT-Americas）评估白细胞总数与 HFpEF 临床结局之间的关系。主要结局是心脏骤停中止、心血管死亡率或心力衰竭住院的复合终点。次要结局是心力衰竭住院、心脏骤停中止、中风、非致命性心肌梗死（MI）、心血管死亡率、非心血管死亡率和全因死亡率。生存模型用于确定在随访期间白细胞计数高于中位数（7100 个/μL）的患者与白细胞计数低于中位数的患者发生主要和次要结局的风险。TOPCAT-Americas 中共有 1746 名（1767 名中的 99%）患者可进行分析，中位随访时间为 2.4 年（25 至 75 百分位数为 1.4-3.9）。白细胞计数>7100 个/μL 的患者发生主要终点的可能性比白细胞计数≤7100 个/μL 的患者高 36%（危险比：1.36，95%置信区间：1.14-1.61）。在对潜在混杂因素进行广泛调整后，这种关联仍然显著（危险比：1.27，95%置信区间：1.06-1.52）。我们还观察到白细胞计数较高的患者心力衰竭住院和非致命性 MI 的发生率更高。这些关联在敏感性分析中仍然稳健，表明混杂的可能性较低。探索性分析表明，在同一模型中，白细胞计数升高（整合骨髓和淋巴免疫细胞的综合影响）和血小板计数升高（作为骨髓免疫细胞扩张的替代指标）均与主要结局相关（均 P<0.05）。
白细胞计数>7100 个/μL 与来自 TOPCAT-Americas 的 HFpEF 患者的不良临床结局独立相关。这些结果主要由心力衰竭住院结局驱动，但也伴有非致命性 MI 增加。需要进一步研究以确定我们研究结果的机制及其预后意义。
