Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
J Card Fail. 2020 Mar;26(3):233-242. doi: 10.1016/j.cardfail.2020.01.003. Epub 2020 Jan 11.
Patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status.
Among 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (β coefficient per 1 SD decrease in eGFR: -0.61, 95% CI: -1.01, -0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (β coefficient: -0.26, 95% CI: -0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO. Sildenafil therapy was independently associated with worsening eGFR over the trial (β coefficient: -2.79, 95% CI: -5.34, -0.24, P = .03).
Renal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.
射血分数保留的心力衰竭（HFpEF）和慢性肾脏病（CKD）患者代表了一种高风险表型。磷酸二酯酶-5 抑制改善射血分数保留的心力衰竭患者的临床状况和运动能力（RELAX）试验纳入了大量 CKD 参与者，允许根据 CKD 状态研究 HFpEF 的差异。
在 212 名参与者中，我们研究了 CKD 与生物标志物、心脏结构和运动能力的关系，并确定了试验随访过程中估计肾小球滤过率（eGFR）变化的预测因素。CKD 参与者（eGFR≤60mL/min/1.73m）年龄较大，合并症较多，舒张功能较差。较低的 eGFR 与较高水平的内皮素-1、N 末端 pro-B 型利钠肽、醛固酮、尿酸和纤维化生物标志物相关（所有 P 值均<.05）。然而，在调整人口统计学、临床合并症、运动方式、射血分数和变时指数后，较低的 eGFR 与峰值耗氧量（VO）较差相关（eGFR 每降低 1 个标准差的β系数：-0.61，95%CI：-1.01，-0.22，P=.002），但在进一步调整血红蛋白后，这种相关性减弱（β系数：-0.26，95%CI：-0.68，0.16，P=.22）。血红蛋白介导了 eGFR 与峰值 VO 之间 35%的关联。西地那非治疗与试验期间 eGFR 的恶化独立相关（β系数：-2.79，95%CI：-5.34，-0.24，P=.03）。
HFpEF 中的肾功能障碍表现为超声心动图和生物标志物特征，提示疾病更严重，而血红蛋白降低是肾功能障碍与低运动能力之间关联的一个强有力的中介因素。西地那非治疗与 RELAX 中肾功能恶化相关。
