Abstract：
In people at risk of heart failure (HF) enrolled in the Heart \'OMics\' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia.
The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium < 4.0 mmol/L, 367 had potassium 4.0-5.0 mmol/L, and 58 had potassium > 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium < 3.5 mmol/L was observed in 6 (1.2%) and <4.0 mmol/L in 46 (9%) participants, while a potassium > 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at <4.0 and >5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration < 4.0 mmol/L was positively associated with the use of thiazides (OR: 2.39 [95% CI 1.32; 4.34]), blood urea concentration (OR: 2.15 [95% CI 1.34; 3.39] per 10 mg/dL), and history of hypertension (OR: 2.32 [95% CI 1.02; 5.29]) and negatively associated with randomization to spironolactone (OR: 0.30 [95% CI 0.18; 0.52]).
In people at risk for developing HF and with relatively normal renal function, spironolactone reduced the risk of hypokalaemia and, at the doses used, was not associated with the occurrence of clinically meaningful hyperkalaemia.
The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium < 4.0 mmol/L, 367 had potassium 4.0-5.0 mmol/L, and 58 had potassium > 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium < 3.5 mmol/L was observed in 6 (1.2%) and <4.0 mmol/L in 46 (9%) participants, while a potassium > 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at <4.0 and >5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration < 4.0 mmol/L was positively associated with the use of thiazides (OR: 2.39 [95% CI 1.32; 4.34]), blood urea concentration (OR: 2.15 [95% CI 1.34; 3.39] per 10 mg/dL), and history of hypertension (OR: 2.32 [95% CI 1.02; 5.29]) and negatively associated with randomization to spironolactone (OR: 0.30 [95% CI 0.18; 0.52]).
In people at risk for developing HF and with relatively normal renal function, spironolactone reduced the risk of hypokalaemia and, at the doses used, was not associated with the occurrence of clinically meaningful hyperkalaemia.
摘要：
目的：在老年（HOMAGE）试验中，在有心力衰竭（HF）风险的人群中，螺内酯减少胶原蛋白合成的循环标记，利钠肽，改善心脏结构和功能。在本报告中，我们探讨了与异常血症相关的因素。
结果：HOMAGE试验是一项开放标签研究，比较有HF风险的人群中螺内酯（最高50mg/天）与标准治疗。随机化后,在1个月和9个月时评估血清钾,当≤3.5mmol/L时定义为低(低钾血症),当≥5.5mmol/L时定义为高(高钾血症).建立多变量logistic回归模型以确定异常血症的临床预测因子。共有513名参与者(平均年龄74岁，75%的男性中位估计肾小球滤过率71mL/min/1.73m2)有血清钾可用,并纳入本分析.在随机化时，88的钾<4.0mmol/L，367含钾4.0-5.0mmol/L，58的钾>5.0mmol/L随访期间,至少有一次,6例(1.2%)患者血清钾<3.5mmol/L,46例(9%)患者血清钾<4.0mmol/L,而在38例（8%）和5例（1.0%）参与者中观察到钾>5.0mmol/L。研究期间使用螺内酯的血清钾增加的中位数（百分位数25-75）为0.23（0.16；0.29）mmol/L。因为异常血症的发生率很低，对于回归分析，低钾血症和高钾血症阈值设定为<4.0和>5.0mmol/L，分别。随访期间血清钾>5.0mmol/L的发生与糖尿病{比值比[OR]:1.21[95%置信区间(CI)2.14;3.79]}和随机选择螺内酯(OR:2.83[95%CI1.49;5.37])的存在正相关。相反，钾浓度<4.0mmol/L的发生与噻嗪类的使用呈正相关(OR:2.39[95%CI1.32;4.34]),血尿素浓度（OR：2.15[95％CI1.34;3.39]每10mg/dL），和高血压病史（OR：2.32[95％CI1.02;5.29]），与随机选择螺内酯呈负相关（OR：0.30[95％CI0.18;0.52]）。
结论：在有发展为HF的风险且肾功能相对正常的人群中，螺内酯降低了低钾血症的风险，在使用的剂量下，与有临床意义的高钾血症的发生无关。
结果：HOMAGE试验是一项开放标签研究，比较有HF风险的人群中螺内酯（最高50mg/天）与标准治疗。随机化后,在1个月和9个月时评估血清钾,当≤3.5mmol/L时定义为低(低钾血症),当≥5.5mmol/L时定义为高(高钾血症).建立多变量logistic回归模型以确定异常血症的临床预测因子。共有513名参与者(平均年龄74岁，75%的男性中位估计肾小球滤过率71mL/min/1.73m2)有血清钾可用,并纳入本分析.在随机化时，88的钾<4.0mmol/L，367含钾4.0-5.0mmol/L，58的钾>5.0mmol/L随访期间,至少有一次,6例(1.2%)患者血清钾<3.5mmol/L,46例(9%)患者血清钾<4.0mmol/L,而在38例（8%）和5例（1.0%）参与者中观察到钾>5.0mmol/L。研究期间使用螺内酯的血清钾增加的中位数（百分位数25-75）为0.23（0.16；0.29）mmol/L。因为异常血症的发生率很低，对于回归分析，低钾血症和高钾血症阈值设定为<4.0和>5.0mmol/L，分别。随访期间血清钾>5.0mmol/L的发生与糖尿病{比值比[OR]:1.21[95%置信区间(CI)2.14;3.79]}和随机选择螺内酯(OR:2.83[95%CI1.49;5.37])的存在正相关。相反，钾浓度<4.0mmol/L的发生与噻嗪类的使用呈正相关(OR:2.39[95%CI1.32;4.34]),血尿素浓度（OR：2.15[95％CI1.34;3.39]每10mg/dL），和高血压病史（OR：2.32[95％CI1.02;5.29]），与随机选择螺内酯呈负相关（OR：0.30[95％CI0.18;0.52]）。
结论：在有发展为HF的风险且肾功能相对正常的人群中，螺内酯降低了低钾血症的风险，在使用的剂量下，与有临床意义的高钾血症的发生无关。
