A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome
A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome
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DOI：
10.1016/j.jcmg.2011.08.014
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发表时间：
2011-12-01
影响因子：
14
通讯作者：
Marwick, Thomas H.
中科院分区：
文献类型：
--
作者：
Kosmala, Wojciech;Przewlocka-Kosmala, Monika;Marwick, Thomas H.
本研究的目的是确定螺内酯对服用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的代谢综合征（MS）患者的左心室（LV）结构和功能以及血清纤维化标志物的影响。方法80例MS患者（年龄59 +/-11岁），已接受血管紧张素II抑制剂治疗，随机分为螺内酯25 mg/d组和安慰剂组，治疗6个月。每例患者均接受基线和随访常规超声心动图和彩色组织多普勒成像。原始数据文件用于测量校准后的背向散射积分并计算径向和纵向应变。在基线和随访时取血测定纤维化标志物（III型前胶原氨基末端前肽和I型前胶原羧基末端前肽[PICP]）。结果螺内酯组显示左室功能、心肌反射率和左室肥厚显著改善，PICP和III型前胶原氨基末端前肽水平平行降低。在安慰剂组中没有观察到类似的变化。基线应变（β = 0.47，p < 0.0001）、螺内酯治疗（β =-0.38，p < 0.0001）和PICP水平变化（β =-0.19，p < 0.03）与LV收缩功能改善（应变增加）独立相关。左室舒张功能改善的相关因素（舒张早期二尖瓣环速度增加）为基线舒张早期二尖瓣环速度（β = 0.47，p < 0.0001）、螺内酯治疗（β =-0.21，p < 0.03）、PICP水平变化（β =-0.23，p < 0.02）和年龄（β = 0.22，p < 0.04）。在纤维化程度较轻的患者中，螺内酯对心功能的有利影响未得到证实（较低基线PICP三分位数）或保留功能（基线应变三分位数上限）结论：在标准的血管紧张素II抑制剂基础上加用螺内酯可改善MS患者的心肌异常，降低纤维化标志物。对干预的回应。（J Am科尔心脏病学杂志2011;4：1239-49）（C）美国心脏病学会基金会2011年
OBJECTIVES The purpose of this study was to identify the effects of spironolactone on left ventricular (LV) structure and function, and serological fibrosis markers in patients with metabolic syndrome (MS) taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.BACKGROUND Myocardial fibrosis may be an important contributor to myocardial impairment in MS, and aldosterone antagonism may reduce fibrosis.METHODS Eighty patients (age 59 +/- 11 years) with MS, already being treated with angiotensin II inhibition, were randomized to spironolactone 25 mg/day or placebo for 6 months. Each patient underwent baseline and follow-up conventional echocardiography and color tissue Doppler imaging. Raw data files were used to measure calibrated integrated backscatter and to calculate radial and longitudinal strain. Blood was obtained at baseline and follow-up to measure fibrosis markers (procollagen type III amino-terminal propeptide and procollagen type I carboxy-terminal propeptide [PICP]).RESULTS The spironolactone group showed significant improvement of LV function, myocardial reflectivity, and LV hypertrophy, with a parallel decrease in levels of PICP and procollagen type III amino-terminal propeptide. No analogous changes were seen in the placebo group. Baseline strain (beta = 0.47, p < 0.0001), spironolactone therapy (beta = -0.38, p < 0.0001), and change in PICP level (beta = -0.19, p < 0.03) were independently associated with LV systolic function improvement (increase in strain). Correlates of LV diastolic function improvement (increase in early diastolic mitral annular velocity) were baseline early diastolic mitral annular velocity (beta = 0.47, p < 0.0001), spironolactone therapy (beta = -0.21, p < 0.03), change in PICP level (beta = -0.23, p < 0.02), and age (beta = 0.22, p < 0.04). Favorable effects of spironolactone on cardiac function were not demonstrated in patients with less fibrosis (the lower baseline PICP tertile) or preserved function (the upper baseline strain tertile).CONCLUSIONS Addition of spironolactone to standard angiotensin II inhibition improved myocardial abnormalities and decreased fibrotic markers in MS. The magnitude of benefit on cardiac performance is determined mainly by baseline LV dysfunction and collagen turnover as well its response to intervention. (J Am Coll Cardiol Img 2011;4:1239-49) (C) 2011 by the American College of Cardiology Foundation