Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Eur J Heart Fail. 2018 Oct;20(10):1436-1443. doi: 10.1002/ejhf.1229. Epub 2018 Jun 12.
Prior cohorts demonstrating the importance of serum chloride levels in heart failure either excluded or had partial representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between serum chloride concentration and outcomes in HFpEF.
We included participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) who met the following criteria: met inclusion by the natriuretic peptide stratum, had recorded serum chloride levels, and were from the Americas (n = 942). Multivariable Cox proportional hazards models tested the association of serum chloride with clinical outcomes, and mixed effects modelling tested the association of spironolactone or loop diuretic on serial serum chloride levels. The median serum chloride level was 102 [25th-75th percentile 100-105 mmol/L (range 84-114 mmol/L)]. After multivariable adjustment, every standard deviation decrease in serum chloride (4.05 mmol/L) was associated with ∼50% increased risk for cardiovascular death [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11-2.06, P = 0.008] and ∼30% increased risk for all-cause death (HR 1.29, 95% CI 1.02-1.62, P = 0.04), but not with the primary composite endpoint or heart failure hospitalization (P > 0.3 for both). There were no significant interactions between spironolactone use and the serum chloride-risk relationship (P > 0.1) for each endpoint. Spironolactone was not (P = 0.33) but loop diuretic use was associated with lower serial serum chloride levels (P < 0.001).
Lower serum chloride was independently associated with increased risk of cardiovascular and all-cause death in HFpEF. Loop diuretic use, but not spironolactone, lead to a decrease in serum chloride levels over time.
先前的队列研究表明血清氯水平在心力衰竭中的重要性，但这些研究要么排除了射血分数保留型心力衰竭（HFpEF）患者，要么只部分纳入了这些患者。本研究旨在探讨血清氯浓度与 HFpEF 患者结局的关系。
我们纳入了来自治疗射血分数保留型心力衰竭的醛固酮拮抗剂试验（TOPCAT）的符合以下标准的参与者：符合利钠肽分层纳入标准、记录了血清氯水平且来自美洲的患者（n=942）。多变量 Cox 比例风险模型检验了血清氯与临床结局的相关性，混合效应模型检验了螺内酯或袢利尿剂对血清氯连续水平的影响。血清氯中位数为 102 [25 至 75 百分位数为 100-105mmol/L（范围 84-114mmol/L）]。经多变量校正后，血清氯每降低一个标准差（4.05mmol/L），心血管死亡风险增加约 50%[风险比（HR）1.51，95%置信区间（CI）1.11-2.06，P=0.008]，全因死亡风险增加约 30%（HR 1.29，95% CI 1.02-1.62，P=0.04），但与主要复合终点或心力衰竭住院无关（两者 P>0.3）。在每个终点，螺内酯的使用与血清氯风险关系之间均无显著交互作用（P>0.1）。螺内酯无此作用（P=0.33），但袢利尿剂的使用与血清氯水平的逐渐降低相关（P<0.001）。
较低的血清氯与 HFpEF 患者心血管死亡和全因死亡风险的增加独立相关。袢利尿剂的使用，而非螺内酯，会导致血清氯水平随时间逐渐降低。
