依泽替米贝联合阿托伐他汀治疗非酒精性脂肪性肝病合并冠心病患者疗效初步研究*

doi:10.3969/j.issn.1672-5069.2018.03.022

摘要/Abstract

摘要： 目的探讨依泽替米贝联合阿托伐他汀治疗非酒精性脂肪性肝病(NAFLD )合并冠心病患者的疗效。方法 2014年2月~2016年2月我院收治的NAFLD合并冠心病患者114例,被随机分为观察组和对照组,每组57例,分别接受依泽替米贝联合阿托伐他汀钙片或阿托伐他汀治疗6 m。使用Philips HD 6型彩色多普勒超声诊断仪检测左心室射血分数（LVEF）、左心室舒张末期直径（LVVED）和左心室后壁厚度（LVPWd）;采用高效液相色谱法检测血清非对称性二甲基精氨酸（ADMA）水平,采用ELISA 法检测血清白介素-6（IL-6）和白介素-10（IL-10）水平。结果在治疗6 m末,观察组血清TC、TG、LDL-C水平分别为（4.3±1.6） mmol/L、（2.4±0.9） mmol/L和（2.8±1.1） mmol/L,显著低于对照组的（5.1±1.7） mmol/L、（2.9±0.9） mmol/L和（3.3±1.2） mmol/L（P<0.05）,血清HDL-C水平为（1.3±0.5） mmol/L,显著高于对照组的（1.0±0.4） mmol/L（P<0.05）;观察组血清肝功能指标改善显著优于对照组（P<0.05）;观察组LVEF为（47.2±6.4）%,显著高于对照组的（42.8±5.8）%（P<0.05）,LEVDD和LVPWd分别为（52.5±7.3） mm和（10.1±0.9） mm,显著低于对照组的（58.2±7.6） mm和（11.4±1.1） mm（P<0.05）;观察组血清ADMA、hs-CRP和IL-6水平分别为（2.8±0.4） μmol/L、（3.4±0.7） mg/L和（39.3±6.9）ng/L,显著低于对照组的（3.0±0.4） μmol/L、（3.9±0.7） mg/L和（45.9±8.4） ng/L（P<0.05）,血清IL-10水平为（28.7±8.6）ng/L,显著高于对照组的（22.3±5.4） ng/L（P<0.05）。结论依泽替米贝联合阿托伐他汀治疗NAFLD合并冠心病患者可明显降低血脂,改善肝功能,可能与其调控脂质代谢,降低血清ADMA和炎性因子水平有关。

关键词: 非酒精性脂肪性肝病, 冠心病, 依泽替米贝, 阿托伐他汀, 疗效

Abstract: Objective To investigate the efficacy of combination of ezetimibe and atorvastatin in treatment of patients with nonalcoholic fatty liver disease （NAFLD） complicated by coronary heart disease （CHD）. Methods 114 patients with NAFLD and CHD were recruited in our hospital between February 2014 and February 2016,and were randomly divided into the observation group and the control group with 57 cases in each group by a computer-generated numbers. The patients in the control group were given atorvastatin calcium,and those in the observation group were given combination of ezetimibe and atorvastatin therapy for six months. The left ventricular ejection fraction（LVEF）,left ventricular end-diastolic diameter（LVVED） and left ventricular posterior wall depth （LVPWd） were obtained by echocardiography,and serum interleukin -6（IL-6） and interleukin-10 （IL-10） were assayed by ELISA. Results At the end of six month observation,serum TC,TG and LDL-C levels were（4.3±1.6） mmol/L,（2.4±0.9） mmol/L and （2.8±1.1） mmol/L,respectively in the observation group, significantly lower than （5.1±1.7） mmol/L,（2.9±0.9） mmol/L and （3.3±1.2） mmol/L （P<0.05） in the control group,while serum HDL-C level was （1.3±0.5） mmol/L,significantly higher than （1.0±0.4） mmol/L（P<0.05） in the control group;serum ALT,AST and GGT levels decreased significantly in the observation（P<0.05）;the LVEF was（47.2±6.4）%,significantly higher than（42.8 ±5.8）% （P<0.05）,while LEVDD and LVPWd were（52.5±7.3） mm and（10.1±0.9） mm,significantly lower than （58.2±7.6） mm and （11.4±1.1） mm,respectively （P<0.05） in the control;serum levels of ADMA,hs-CRP and IL-6 were （2.8±0.4） μmol/L,（3.4±0.7） mg/L and （39.3±6.9） ng/L,significantly lower than （3.0±0.4） μmol/L,（3.9±0.7） mg/L and （45.9±8.4） ng/L （P<0.05） in the control and serum level of IL-10 was （28.7±8.6） ng/L,significantly higher than （22.3±5.4） ng/L（P<0.05） in the control group. Conclusion s Ezetimibe combined with atorvastatin could significantly decrease the serum lipid levels and improve liver functions in patients with NAFLD complicated by CHD,which might be related to the regulation of lipid metabolism and reduced levels of ADMA and serum inflammatory factors.

Key words: Nonalcoholic fatty liver disease, Coronary heart disease, Ezetimibe, Atorvastatin, Efficacy

李彩虹, 连琳琳, 路德荣. 依泽替米贝联合阿托伐他汀治疗非酒精性脂肪性肝病合并冠心病患者疗效初步研究*[J]. 实用肝脏病杂志, 2018, 21(3): 405-408.

Li Caihong, Lian Lingling, Lu Derong. Preliminary trial of ezetimibe combined with atorvastatin in treatment of patient with nonalcoholic fatty liver disease complicated by coronary heart disease[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 405-408.

参考文献

[1] 管军,徐烨. 青少年非酒精性脂肪肝相关危险因素分析. 实用肝脏病杂志,2017,20(3):347-349.
[2] Gaggini M,Morelli M,Buzzigoli E,et al.Non-alcoholic fatty liver disease(NAFLD) and its connection with insulin resistance,dyslipidemia,atherosclerosis and coronary heart disease. Nutrients,2013,5(5):1544-1560.
[3] Rosen JB,Ballantyne CM,Hsueh WA,et al.Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk. Lipids Health Dis,2015,14(1):103.
[4] Sánchezpolo MT,Castells MT,Garcíapérez B,et al.Effect of diet/atorvastatin on atherosclerotic lesions associated to nonalcoholic fatty liver disease in chickens. Histol Histopathol,2015,30(12):1439-1446.
[5] Stone NJ,Robinson JG,Lichtenstein AH,et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults:synopsis of the2013 american college of cardiology/american heart association cholesterol guideline. Ann Intern Med,2014,160(5):339.
[6] Masuda J,Tanigawa T,Nakata T,et al.Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in Japanese patients with stable coronary artery disease. Int Heart J,2015,56(3):278-285.
[7] 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南. 实用肝脏病杂志,2007,10(1):1-3.
[8] 中华心血管病杂志编辑委员会. 不稳定性心绞痛诊断和治疗建议中华医学会心血管病学分会. 中华心血管病杂志,2000,28(6):409-412.
[9] Ampuero J,Gallegodurán R,Romerogómez M.Association of NAFLD with subclinical atherosclerosis and coronary-artery disease:meta-analysis. Rev Esp Enferm Dig,2015,107(1):10-16.
[10] Mikolasevic I,Orlic L,Milic S,et al.Nonalcoholic fatty liver disease(NAFLD) proven by transient elastography in patients with coronary heart disease. Wien Klin Wochenschr,2014,126(15-16):474-479.
[11] Kim HJ,Kim JH,Choe WH,et al.Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population:a cross-sectional study. Clin Mol Hepatol,2014,20(2):154-161.
[12] Satoh M,Tabuchi T,Itoh T,et al.NLRP3 inflammasome activation in coronary artery disease:results from prospective and randomized study of treatment with atorvastatin or rosuvastatin. Clin Sci,2014,126(3):233-241.
[13] Tsujita K,Sugiyama S,Sumida H,et al.Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention:The multicenter randomized controlled precise-ivus trial. J Am Coll Cardiol,2015,66(5):495-507.
[14] Wang X,Zhao X,Li L,et al.Effects of combination of ezetimibe and rosuvastatin on coronary artery plaque in patients with coronary heart disease. Heart Lung Circ,2016,25(5):459-465.
[15] Cannon CP.Improve-it trial:a comparison of ezetimibe/simvast-atin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. Circulation,2014,130(23):2109.
[16] 杨伟,腾林,喻红. 依泽替米贝联合阿托伐他汀对动脉粥样硬化斑块的影响. 中国医院药学杂志,2016,36(22):2007-2011.
[17] Fallatah HI,Akbar HO,Fallatah AM.Fibroscan compared to fib-4,apri,and ast/altratio for assessment of liver fibrosis in saudi patients with nonalcoholic fatty liver disease. Hepat Mon,2016,16(7):e38346.
[18] Sert A,Pirgon O,Aypar E,et al.Relationship between aspartate aminotransferase-to-platelet ratio index and carotid intima- media thickness in obese adolescents with non-alcoholic fatty liver disease. J Clin Res Pediatr Endocrinol,2013,5(3):182-188.
[19] O'Doherty MG,Gilchrist S E,Young IS,et al. Effect of supplementation with b vitamins and antioxidants on levels of asymmetric dimethylarginine (adma) and c-reactive protein (crp):a double-blind,randomised,factorial design,placebo-controlled trial. Eur J Nutr,2010,49(8):483-492.
[20] Musso G,Cassader M,Gambino R.Cholesterol-lowering therapy for the treatment of nonalcoholic fatty liver disease:an update. Curr Opin Lipidol,2011,22(6):489-496.
[21] Vaverkova H,Farnier M,Averna M,et al.Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared to rosuvastatin 10 mg in high-risk patients with and without type 2 diabetes mellitus inadequately controlled despite prior statin monotherapy. Cardiovasc Ther,2012,30(2):61-74.