Ferreira João Pedro, Claggett Brian L, Liu Jiankang, Desai Akshay S, Pfeffer Marc A, Anand Inder S, van Veldhuisen Dirk J, Kober Lars, Cleland John G F, Rouleau Jean L, Packer Milton, Zile Michael R, Shi Victor C, Lefkowitz Martin P, Shah Sanjiv J, Vardeny Orly, Zannad Faiez, Solomon Scott D, McMurray John J V
National Institute of Health and Medical Research, Center for Clinical Multidisciplinary Research, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Nancy, France.
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Eur J Heart Fail. 2021 May;23(5):776-784. doi: 10.1002/ejhf.2134. Epub 2021 Mar 8.
The relationship between serum potassium concentration and outcomes in patients with heart failure and preserved ejection fraction (HFpEF) is not well-established. The aim of this study was to explore the association between serum potassium and clinical outcomes in the PARAGON-HF trial in which 4822 patients with HFpEF were randomised to treatment with sacubitril/valsartan or valsartan.
The relationship between serum potassium concentrations and the primary study composite outcome of total (first and recurrent) heart failure hospitalisations and cardiovascular death was analysed. Hypo-, normo-, and hyperkalaemia were defined as serum potassium <4 mmol/L, 4-5 mmol/L and >5 mmol/L, respectively. Both screening and time-updated potassium (categorical and continuous spline-transformed) were studied. Patient mean age was 73 years and 52% were women. Patients with higher baseline potassium more often had an ischaemic aetiology and diabetes and mineralocorticoid receptor antagonist treatment. Compared with normokalaemia, both time-updated (but not screening) hypo- and hyperkalaemia were associated with a higher risk of the primary outcome [adjusted hazard ratio (HR) for hypokalaemia 1.55, 95% confidence interval (CI) 1.30-1.85; P < 0.001, and for hyperkalaemia HR 1.21, 95% CI 1.02-1.44; P = 0.025]. Hypokalaemia had a stronger association with a higher risk of all-cause, cardiovascular and non-cardiovascular death than hyperkalaemia. The association of hypokalaemia with increased risk of all-cause and cardiovascular death was most marked in participants with impaired kidney function (interaction P < 0.05). Serum potassium did not significantly differ between sacubitril/valsartan and valsartan throughout the follow-up.
Both hypo- and hyperkalaemia were associated with heart failure hospitalisation but only hypokalaemia was associated with mortality, especially in the context of renal impairment. Hypokalaemia was as strongly associated with death from non-cardiovascular causes as with cardiovascular death. Collectively, these findings suggest that potassium disturbances are a more of a marker of HFpEF severity rather than a direct cause of death.
射血分数保留的心力衰竭（HFpEF）患者血清钾浓度与预后之间的关系尚未明确确立。本研究的目的是在PARAGON-HF试验中探讨血清钾与临床预后之间的关联，该试验中4822例HFpEF患者被随机分配接受沙库巴曲缬沙坦或缬沙坦治疗。
分析血清钾浓度与主要研究复合结局（首次及再发）心力衰竭住院和心血管死亡之间的关系。低钾血症、正常血钾和高钾血症分别定义为血清钾<4 mmol/L、4 - 5 mmol/L和>5 mmol/L。研究了筛查时的钾以及随时间更新的钾（分类和连续样条转换）。患者平均年龄为73岁，52%为女性。基线血钾较高的患者更常患有缺血性病因、糖尿病并接受盐皮质激素受体拮抗剂治疗。与正常血钾相比，随时间更新的（而非筛查时的）低钾血症和高钾血症均与主要结局风险较高相关[低钾血症的调整后风险比（HR）为1.55，95%置信区间（CI）为1.30 - 1.85；P < 0.001，高钾血症的HR为1.21，95% CI为1.02 - 1.44；P = 0.025]。低钾血症与全因、心血管和非心血管死亡风险较高的关联比高钾血症更强。低钾血症与全因和心血管死亡风险增加的关联在肾功能受损的参与者中最为明显（交互作用P < 0.05）。在整个随访期间，沙库巴曲缬沙坦和缬沙坦组之间的血清钾无显著差异。
低钾血症和高钾血症均与心力衰竭住院相关，但只有低钾血症与死亡率相关，尤其是在肾功能损害的情况下。低钾血症与非心血管原因死亡的关联与心血管死亡一样强烈。总体而言，这些发现表明钾紊乱更多是HFpEF严重程度的一个标志物，而非直接的死亡原因。
