不同剂量瑞舒伐他汀对老年高血压并射血分数保留型慢性心力衰竭患者心室重构的影响

Effects of different doses of rosuvastatin on ventricular remodeling in elderly patients with hypertension and chronic heart failure with preserved ejection fraction

摘要:

目的：探讨不同剂量的瑞舒伐他汀对老年高血压并射血分数保留型慢性心力衰竭（heart failure with preserved ejection fraction，HFpEF）患者心室重构的影响。方法：选择老年高血压并HFpEF患者128例，按照数字表法随机分为２组，在常规心力衰竭治疗的基础上，2组均给予瑞舒伐他汀晚上顿服，低剂量组（64例，10 mg/d）和高剂量组（64例，20 mg/d），2组疗程均为6个月。治疗前及治疗6个月后监测患者的左室重构相关指标[左室舒张末期后壁厚度（left ventricular end-diastolic posterior wall thickness，LVPWT）、舒张末期室间隔厚度（interventricular septum thickness，IVST）、左室质量指数（left ventricular mass index，LVMI）]、左室舒张功能相关指标[左室等容舒张时间（isovolumetric relaxation time，IVRT）、E峰减速时间（deceleration time，DT）、左房容积指数（left atrial volume index，LAVI）、舒张早期二尖瓣血流速度和舒张早期二尖瓣环运动速度的比值（E/E’）]、心功能相关指标[心肌活动指数（Tei指数）、N端B型脑钠肽前体（N-terminal-pro-B-type natriuretic peptide，NT-proBNP）、6 min步行距离（6 minute walking test，6-MWT）]、心肌纤维化相关指标[半乳糖凝集素-3（galectin-3，Gal-3），可溶性ST2（soluble ST2，sST2）、结缔组织生长因子（connective tissue growth factor，CTGF）、转化生长因子-β1（transforming growth factor-β1，TGF-β1）]及炎性反应指标[高敏C反应蛋白（hyper-sensitive C-reactive protein，hs-CRP）、基质金属蛋白酶-9（matrix metalloproteinase-9，MMP-9）、白介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）]水平的变化；记录治疗6个月内主要心脏不良事件及药物不良反应，记录治疗前及治疗每个月后各时间点2组患者的心房纤颤存在例数。结果：治疗6个月后，2组患者的左室重构相关指标（LVPWT、IVST、LVMI）、左室舒张功能相关指标（IVRT、DT、LAVI、E/E’）、心功能相关指标（Tei指数、NT-proBNP、6-MWT）、心肌纤维化相关指标（Gal-3、sST2、CTGF、TGF-β1）及炎性反应指标（hs-CRP、MMP-9、IL-6、TNF-α）均较治疗前明显改善（均P＜0.01），且高剂量组的改善更明显（均P＜0.05）；高剂量组主要心脏不良事件发生率低于低剂量组（χ2=4.195，P=0.041）；2组患者药物不良反应发生率比较无统计学差异（χ2=1.888，P=0.169）；治疗后各时间点2组患者的心房纤颤存在率比较无统计学差异（均P＞0.05）。结论：瑞舒伐他汀高剂量比低剂量能更有效改善HFpEF患者的心室重构、心室舒张功能及心功能，降低主要心脏不良事件发生率，且不增加不良反应。瑞舒伐他汀的抗炎、抗心肌纤维化可能为其作用机制之一。

Abstract:

Objective：To investigate the effects of different doses of rosuvastatin on ventricular remodeling in elderly patients with hypertension and chronic heart failure with preserved ejection fraction（HFpEF）. Methods：A total of 128 elderly patients with hyper－tension and HFpEF were randomized into two groups，the low-dose group（64 cases，10 mg/d） and the high-dose group（64 cases，20 mg/d），based on conventional treatment for heart failure，both groups were given rosuvastatin at night，and the treatment period of both groups was 6 months. Before and 6 months after treatment，we monitored changes in the levels of left ventricular remodeling related indexes in patients including left ventricular end-diastolic posterior wall thickness（LVPWT），interventricular septum thickness （IVST），and left ventricular mass index（LVMI），left ventricular diastolic function related indicators including isovolumetric relaxation time（IVRT），deceleration time（DT），left atrial volume index（LAVI），and E/E'，cardiac function related indicators including Tei index，N-terminal-pro-B-type natriuretic peptide（NT-proBNP），and 6 minute walking test（6-MWT），myocardial fibrosis related indicators including galectin-3（Gal-3），soluble ST2（sST2），connective tissue growth factor（CTGF），and transforming growth factor-β1（TGF-β1） and inflammatory response indicators including hyper-sensitive C-creative protein（hs-CRP），matrix metallopro－teinase-9（MMP-9），interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α）. Major cardiac adverse events and adverse drug reactions were recorded within 6 months of treatment. The number of patients with atrial fibrillation at each time point before and after treatment was recorded in both groups. Results：Six months after treatment，left ventricular remodeling in patients（LVPWT，IVST，LVMI），left ventricular diastolic function related indicators（IVRT，DT，LAVI，E/E’），cardiac function related indicators（Tei index，NT-proBNP，6-MWT），myocardial fibrosis related indicators（Gal-3，sST2，CTGF，TGF-β1） and inflammatory response indicators（hs-CRP，MMP-9，IL-6，TNF-α） were significantly better than those before treatment（all P＜0.01），the improvement was more significant in the high-dose group（all P＜0.05）. The incidence of major adverse cardiac events in the high-dose group was lower than that in the low-dose group（χ2=4.195，P=0.041）. There was no significant difference in the incidence of adverse drug reactions between two groups（χ2=1.888，P=0.169），and in the existence rate of atrial fibrillation between two groups at each time point after treatment（all P＞0.05）. Conclusion：Compared with the low dose，the high dose of rosuvastatin can effectively improve the ventricular remodeling，ventricular diastolic function and cardiac function in HFpEF patients，and reduce the incidence of major adverse cardiac events without increasing adverse reactions. The anti-inflammatory and anti-myocardial fibrosis of rosuvastatin may be one of its mechanisms.