螺内酯对心房颤动单核细胞亚群的影响：IMPRESS-AF随机对照试验
Effect of spironolactone on monocyte subsets in atrial fibrillation: IMPRESS-AF randomised controlled trial.
作者信息
Shahid Farhan, Shantsila Eduard, Shantsila Alena, Lip Gregory Y H
机构信息
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Departments of Primary care and Mental Health, University of Liverpool, Liverpool, UK.
出版信息
Sci Rep. 2025 Jul 28;15(1):27410. doi: 10.1038/s41598-024-74592-1.
BACKGROUND
Monocyte subsets differentially influence pathophysiology of heart failure and atrial fibrillation (AF) through inflammation, fibrosis, and angiogenesis. Spironolactone has antifibrotic properties. This study investigated the effect spironolactone on monocyte subsets and monocyte effects for peak oxygen consumption (peakVO2), diastolic function and brain natriuretic peptide (BNP) in the IMPRESS-AF randomised controlled trial population (2-year treatment with spironolactone 25 mg vs placebo).
METHODS
CD14++CD16-CCR2+(Mon1), CD14++CD16+CCR2+(Mon2) and CD14+CD16++CCR2-(Mon3) monocyte subsets were analysed by flow cytometry and compared between spironolactone and placebo groups at 12 months and 24 months after randomisation. PeakVO2, diastolic function (echocardiographic E/'e) and BNP were measured at baseline and 24 months. Linear regression was used to assess the effects of monocytes on the outcomes (Python 3.10 modules).
RESULTS
Monocyte data were available in 225 (90%) IMPRESS-AF patients (age 72[67-77], 78% male). At 12-month the spironolactone group had fewer Mon3 (50[36-74] vs 60[44-90] cells/microL, p=0.02), and lower CD14 expression on Mon1 (1.37[1.17-1.59] vs 1.48[1.24-1.70], p=0.04); no difference remained by 24 months (p>0.05). A high 12-month Mon1 count independently predicted lower E/e' at 24 months (p=0.02).
CONCLUSIONS
Spironolactone temporarily reduced proinflammatory monocyte markers (Mon3 count and CD14 expression on Mon1). Mon1 may have a positive effect on diastolic dysfunction in AF.
背景
单核细胞亚群通过炎症、纤维化和血管生成对心力衰竭和心房颤动（AF）的病理生理学产生不同影响。螺内酯具有抗纤维化特性。本研究在IMPRESS-AF随机对照试验人群（2年服用25 mg螺内酯与安慰剂）中，调查了螺内酯对单核细胞亚群的影响以及单核细胞对峰值耗氧量（peakVO2）、舒张功能和脑钠肽（BNP）的作用。
方法
通过流式细胞术分析CD14++CD16-CCR2+（Mon1）、CD14++CD16+CCR2+（Mon2）和CD14+CD16++CCR2-（Mon3）单核细胞亚群，并在随机分组后12个月和24个月时比较螺内酯组和安慰剂组。在基线和24个月时测量peakVO2、舒张功能（超声心动图E/‘e）和BNP。使用线性回归评估单核细胞对结局的影响（Python 3.10模块）。
结果
225例（90%）IMPRESS-AF患者（年龄72[67-77]岁，78%为男性）有单核细胞数据。在12个月时，螺内酯组的Mon3较少（50[36-74]个/微升对60[44-90]个/微升，p=0.02），且Mon1上的CD14表达较低（1.37[1.17-1.59]对1.48[1.24-1.70]，p=0.04）；到24个月时无差异（p>0.05）。12个月时较高的Mon1计数独立预测24个月时较低的E/e’（p=0.02）。
结论
螺内酯可暂时降低促炎单核细胞标志物（Mon3计数和Mon1上的CD14表达）。Mon1可能对AF的舒张功能障碍有积极作用。
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