Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas.
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA Cardiol. 2021 Jan 1;6(1):68-77. doi: 10.1001/jamacardio.2020.5592.
Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear.
To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF.
DESIGN, SETTING, AND PARTICIPANTS: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020.
Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models.
Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44).
In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.
尽管肾功能障碍和血清电解质水平异常与射血分数保留的心力衰竭（HFpEF）患者的临床预后不良相关，但这些实验室指标的随访间变异性与长期结果的关联尚不清楚。
评估慢性稳定型 HFpEF 患者肾功能（肌酐和血尿素氮[BUN]水平）和血清电解质（钠、氯和钾）指数的随访间变异性与不良临床结局风险之间的关系。
设计、设置和参与者：这项队列分析使用了治疗保留心脏功能心力衰竭的醛固酮拮抗剂（TOPCAT）试验的数据。所有纳入的参与者均具有 3 次或以上连续实验室测量值，并且在入组后的前 4 个月内无事件发生。数据于 2019 年 3 月 1 日至 2020 年 1 月 31 日进行分析。
使用 Cox 比例风险回归模型评估随访前 4 个月期间血清实验室测量值的变异性指数与主要复合结局（心搏骤停中止、心力衰竭住院或心血管死亡的复合事件）和全因死亡率风险之间的调整关联。
在 TOPCAT 试验中，共纳入了 3445 名患者（平均[标准差]年龄为 68-69[10]岁；49.7%-51.5%为女性），其中 2479 人（BUN）到 3195 人（钾）进行了分析，具体取决于连续测量值的可用性。肾功能参数随访间变异性较高的患者年龄更大、合并症更多且 HFpEF 的症状更严重。BUN（每 1-SD 平均连续变异性[ASV]增加，HR 为 1.21；95%CI，1.10-1.33）和肌酐（每 1-SD 增加 ASV，HR 为 1.13；95%CI，1.04-1.22）的随访间变异性较高与主要复合结局风险以及死亡率独立相关，独立于其他基线混杂因素、肾功能变化、药物剂量变化以及其他心血管代谢参数（收缩压和体重指数）的变异性。在根据基线时是否存在慢性肾脏病（CKD）对患者进行分层的亚组中，与肾功能变异性较高相关的风险是一致的（CKD：每 1-SD 增加 ASV，HR 为 1.39；95%CI，1.16-1.67；无 CKD：每 1-SD 增加 ASV，HR 为 1.13；95%CI，1.01-1.27），在螺内酯和安慰剂治疗组中分别为（螺内酯组：HR 为 1.30；95%CI，1.03-1.65；安慰剂组：每 1-SD 增加 ASV，HR 为 1.27；95%CI，1.04-1.56）。在血清电解质中，钠和钾测量值的变异性也与主要复合事件风险增加显著相关（钠：每 1-SD 增加 ASV，HR 为 1.14；95%CI，1.01-1.30；钾：每 1-SD 增加 ASV，HR 为 1.21；95%CI，1.02-1.44）。
在 HFpEF 中，肾功能和血清电解质实验室指标的随访间变异性很常见，并且与长期临床结局不良独立相关。
