脂必泰胶囊与阿托伐他汀对血管功能影响的对比研究
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摘要
目的：以阿托伐他汀为阳性对照,观察脂必泰胶囊对心血管高危患者的调脂效应,同时观察其对动脉弹性指标脉搏波速度(Pulse wave velocity, PWV)、踝肱指数(Ankle-brachial index, ABI)及血浆血栓素B2(ThromboxaneB2,TXB2)的影响,分析PWV、ABI、TXB2三者间及各自与血压、血脂的相关性,评价用药安全性。
方法：选2007年7月至2008年12月湘雅二医院心内科门诊就诊,除血脂异常以外至少伴有其他一项心血管危险因素的中老年患者为研究对象,共计83例,随机分为脂必泰组(n=44)和阿托伐他汀组(n=39),分别于治疗前及治疗8周观察血脂、血常规及肝肾功能等指标变化,并于治疗前后采用全自动动脉硬化检测仪测定PWV及ABI,采用酶联免疫吸附法(Enzyme linked immunosorbent assay, ELISA)测定TXB2,分析PWV, ABI、TXB2三者间及各自与血压、血脂的相关性,并观察用药不良反应。
结果：
1.脂必泰胶囊与阿托伐他汀治疗8周,受试者的血清甘油三酯(Triglyceride, TG)、总胆固醇(Total cholesterol, TC)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol, LDL-C)水平均显著降低(P<0.05),而高密度脂蛋白胆固醇(High density lipoprotein cholesterol, HDL-C)水平较治疗前无统计学差异(P>0.05)。两组TG、TC及LDL-C水平降低程度无显著性差异(P>0.05)。
2.脂必泰胶囊和阿托伐他汀治疗8周后,受试者的股-踝脉搏波速度(Femoral-Ankle pulse wave velocity, FAPWV)、颈-桡脉搏波速度(Carotid-Radial pulse wave velocity, CRPWV)显著降低,与治疗前相比有统计学意义(P<0.05),而颈-股脉搏波速度(Carotid-Femur pulse wave velocity, CFPWV)及ABI较治疗前未出现统计学差异(P>0.05)。组间比较上述各值无显著性差异(P>0.05)。
3.脂必泰胶囊和阿托伐他汀治疗8周均使受试者的血浆TXB2浓度显著降低(P<0.05),且两组间TXB2降低程度无显著性差异(P>0.05)。
4.对PWV、ABI、血浆TXB2与血压、血脂相关性分析发现,CFPWV与收缩压(Systolic blood pressure, SBP)呈正相关(r=0.273,p=0.014),而CRPWV与舒张压(Diastolic blood pressure, DBP)呈正相关(r=0.341,p=0.002)；血浆TXB2浓度与SBP、TC及LDL-C均呈正相关(r分别为0.272、0.363、0.297,p分别为0.030、0.003、0.017), FAPWV、ABI与血压、血脂水平均无相关性；两组CRPWV、FAPWV下降值及血浆TXB2浓度改变与血压、血脂基础水平及血脂改变量均无相关性。对PWV、ABI、血浆TXB2基础值三者间的相关性进行分析,结果显示CFPWV与血浆TXB2浓度呈正相关(r=0.303,p=0.016), FAPWV与ABI呈负相关(r=-0.248,p=0.028)。
5.脂必泰胶囊治疗8周使受试者谷丙转氨酶(Alanine aminotransferase, ALT)、总胆红素(Total bilirubin, TBIL)及空腹血糖(Fasting blood sugar, FBS)明显降低(P<0.05),而阿托伐他汀组以上指标较治疗前无统计学差异(P>0.05)。两组治疗前后,血常规、肾功能等均无明显变化。
6.阿托伐他汀组有1例患者治疗未满4周时出现肝区疼痛,退出研究。脂必泰胶囊组无严重或无法耐受的不良事件发生,患者耐受性较好。
结论：
1.脂必泰胶囊和阿托伐他汀治疗8周均能有效降低心血管高危患者的TG、TC、LDL-C水平,二者降低TG、TC和LDL-C的程度相近。
2.脂必泰胶囊和阿托伐他汀治疗8周对反映外周中等肌性动脉弹性指标CRPWV及FAPWV均有降低作用,而对ABI及中央大动脉弹性指标CFPWV均无明显影响。
3.两者均能显著降低患者血浆TXB2浓度,提示血小板活性降低,血栓素A2(ThromboxaneA2,TXA2)对血管的强烈收缩作用在一定程度上改善。
4.脂必泰胶囊对ALT及TBIL升高的肝功能异常患者可能有益,且有辅助降血糖作用,阿托伐他汀短期治疗无以上作用。
5.脂必泰胶囊不良反应甚少,患者耐受性好。
Objectives:The aim of this study was to evaluate the effects of Zhibitai capsule on blood lipids,arterial elasticity(measured by pulse wave velocity(PWV) and ankle-brachial index(ABI)) and plasma thromboxaneB2(TXB2) in patients with high cardiovascular risk, compared with Atorvastatin.The safety of Zhibitai capsule and Atorvastatin were assessed after 8-week treatment.
Methods:Eighty three subjects with high risk factors of cardiovascular disease were randomizedly devided into Zhibitai group (n=44) and Atorvastatin group (n=39),and the course of treatment was eight weeks.The levels of blood lipids were assayed by clinical chemistry method. PWV and ABI were measured with an automatic device.Plasma TXB2 levels were measured with enzyme linked immunosorbent assay before and after treatment,respectively.The safety and tolerability of Zhibitai and Atorvastatin were evaluated at the end of the treatment.
Results:
1. In the two groups,the levels of triglyeride(TG),total cholesterol (TC) and low density lipoprotein cholesterol(LDL-C) were decreased markedly for 8 weeks (P< 0.05),but high density lipoprotein cholesterol (HDL-C) had no significant change (P>0.05).The variation of the TG, TC and LDL-C levels had no difference between two groups (P>0.05)
2. Femoral-ankle PWV(FAPWV) and carotid-radial PWV(CRPWV) were decreased markedly after therapy with both Zhibitai capsule and Atorvastatin (P<0.05).No significant difference was found between the two groups (P>0.05). There were no obvious change in carotid-femoral PWV(CFPWV) and ABI in two groups (P>0.05)
3. Plama TXB2 levels were reduced observably in two groups after therapy (P<0.05).The variation of the TXB2 levels had no difference between two groups (P>0.05)
4. CFPWV was correlated with systolic blood pressure (SBP) (r=0.273,p=0.014),while CRPWV was correlated with diastolic blood pressure (DBP) (r=0.341,p=0.002).Plasma TXB2 level was correlated with SBP (r=0.272,p=0.030),TC (r=0.363,p=0.003),and LDL-C (r=0.297,p=0.017). There were no correlation between blood pressure,blood lipids and FAPWV,ABI. No significant association was observed between the extent of lipid reduction and fall in CRPWV, FAPWV or plasma TXB2. CFPWV and plasma TXB2 level were positively correlated(r=0.303,p=0.016),while FAPWV and ABI were negatively correlated (r=-0.248,p=0.028).
5 The levels of alanine aminotransferase (ALT),total bilirubin (TBIL) and fasting blood sugar (FBS) were decreased evidently after therapy with Zhibitai for 8 weeks (P<0.05), but there were no significant alteration of them in Atorvastatin group (P>0.05).No significant changes of blood regulation and kidney function were found in two groups (P> 0.05).
6. In Atorvastatin group,one patient withdrew from the study because of the liver pain.The side effects of Zhibitai were very mild, and the compliance of patients was very well.
Conclusions:
1. Zhibitai capsule has the same effects on reducing serum levels of TG,TC and LDL-C as Atorvastatin after 8 week treatment.
2. Both Atorvastatin and Zhibitai can reduce the levels of FAPWV and CRPWV significantly, thus improving peripheral muscular medium-sized arterial elasticity,while ABI and CFPWV were not changed in the two groups.
3. The level of plasma TXB2 was reduced obviously in the two groups after 8 week treatment suggesting that platelet activation and the contraction of thromboxane A2 (TXA2) on vasvular system may be reduced to some extent.
4. Zhibitai may be effctive in treatment of abnormal liver function and lowering FBS.
5. Zhibitai capsule was relatively safe and the side effects were rare.
方法：选2007年7月至2008年12月湘雅二医院心内科门诊就诊,除血脂异常以外至少伴有其他一项心血管危险因素的中老年患者为研究对象,共计83例,随机分为脂必泰组(n=44)和阿托伐他汀组(n=39),分别于治疗前及治疗8周观察血脂、血常规及肝肾功能等指标变化,并于治疗前后采用全自动动脉硬化检测仪测定PWV及ABI,采用酶联免疫吸附法(Enzyme linked immunosorbent assay, ELISA)测定TXB2,分析PWV, ABI、TXB2三者间及各自与血压、血脂的相关性,并观察用药不良反应。
结果：
1.脂必泰胶囊与阿托伐他汀治疗8周,受试者的血清甘油三酯(Triglyceride, TG)、总胆固醇(Total cholesterol, TC)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol, LDL-C)水平均显著降低(P<0.05),而高密度脂蛋白胆固醇(High density lipoprotein cholesterol, HDL-C)水平较治疗前无统计学差异(P>0.05)。两组TG、TC及LDL-C水平降低程度无显著性差异(P>0.05)。
2.脂必泰胶囊和阿托伐他汀治疗8周后,受试者的股-踝脉搏波速度(Femoral-Ankle pulse wave velocity, FAPWV)、颈-桡脉搏波速度(Carotid-Radial pulse wave velocity, CRPWV)显著降低,与治疗前相比有统计学意义(P<0.05),而颈-股脉搏波速度(Carotid-Femur pulse wave velocity, CFPWV)及ABI较治疗前未出现统计学差异(P>0.05)。组间比较上述各值无显著性差异(P>0.05)。
3.脂必泰胶囊和阿托伐他汀治疗8周均使受试者的血浆TXB2浓度显著降低(P<0.05),且两组间TXB2降低程度无显著性差异(P>0.05)。
4.对PWV、ABI、血浆TXB2与血压、血脂相关性分析发现,CFPWV与收缩压(Systolic blood pressure, SBP)呈正相关(r=0.273,p=0.014),而CRPWV与舒张压(Diastolic blood pressure, DBP)呈正相关(r=0.341,p=0.002)；血浆TXB2浓度与SBP、TC及LDL-C均呈正相关(r分别为0.272、0.363、0.297,p分别为0.030、0.003、0.017), FAPWV、ABI与血压、血脂水平均无相关性；两组CRPWV、FAPWV下降值及血浆TXB2浓度改变与血压、血脂基础水平及血脂改变量均无相关性。对PWV、ABI、血浆TXB2基础值三者间的相关性进行分析,结果显示CFPWV与血浆TXB2浓度呈正相关(r=0.303,p=0.016), FAPWV与ABI呈负相关(r=-0.248,p=0.028)。
5.脂必泰胶囊治疗8周使受试者谷丙转氨酶(Alanine aminotransferase, ALT)、总胆红素(Total bilirubin, TBIL)及空腹血糖(Fasting blood sugar, FBS)明显降低(P<0.05),而阿托伐他汀组以上指标较治疗前无统计学差异(P>0.05)。两组治疗前后,血常规、肾功能等均无明显变化。
6.阿托伐他汀组有1例患者治疗未满4周时出现肝区疼痛,退出研究。脂必泰胶囊组无严重或无法耐受的不良事件发生,患者耐受性较好。
结论：
1.脂必泰胶囊和阿托伐他汀治疗8周均能有效降低心血管高危患者的TG、TC、LDL-C水平,二者降低TG、TC和LDL-C的程度相近。
2.脂必泰胶囊和阿托伐他汀治疗8周对反映外周中等肌性动脉弹性指标CRPWV及FAPWV均有降低作用,而对ABI及中央大动脉弹性指标CFPWV均无明显影响。
3.两者均能显著降低患者血浆TXB2浓度,提示血小板活性降低,血栓素A2(ThromboxaneA2,TXA2)对血管的强烈收缩作用在一定程度上改善。
4.脂必泰胶囊对ALT及TBIL升高的肝功能异常患者可能有益,且有辅助降血糖作用,阿托伐他汀短期治疗无以上作用。
5.脂必泰胶囊不良反应甚少,患者耐受性好。
Objectives:The aim of this study was to evaluate the effects of Zhibitai capsule on blood lipids,arterial elasticity(measured by pulse wave velocity(PWV) and ankle-brachial index(ABI)) and plasma thromboxaneB2(TXB2) in patients with high cardiovascular risk, compared with Atorvastatin.The safety of Zhibitai capsule and Atorvastatin were assessed after 8-week treatment.
Methods:Eighty three subjects with high risk factors of cardiovascular disease were randomizedly devided into Zhibitai group (n=44) and Atorvastatin group (n=39),and the course of treatment was eight weeks.The levels of blood lipids were assayed by clinical chemistry method. PWV and ABI were measured with an automatic device.Plasma TXB2 levels were measured with enzyme linked immunosorbent assay before and after treatment,respectively.The safety and tolerability of Zhibitai and Atorvastatin were evaluated at the end of the treatment.
Results:
1. In the two groups,the levels of triglyeride(TG),total cholesterol (TC) and low density lipoprotein cholesterol(LDL-C) were decreased markedly for 8 weeks (P< 0.05),but high density lipoprotein cholesterol (HDL-C) had no significant change (P>0.05).The variation of the TG, TC and LDL-C levels had no difference between two groups (P>0.05)
2. Femoral-ankle PWV(FAPWV) and carotid-radial PWV(CRPWV) were decreased markedly after therapy with both Zhibitai capsule and Atorvastatin (P<0.05).No significant difference was found between the two groups (P>0.05). There were no obvious change in carotid-femoral PWV(CFPWV) and ABI in two groups (P>0.05)
3. Plama TXB2 levels were reduced observably in two groups after therapy (P<0.05).The variation of the TXB2 levels had no difference between two groups (P>0.05)
4. CFPWV was correlated with systolic blood pressure (SBP) (r=0.273,p=0.014),while CRPWV was correlated with diastolic blood pressure (DBP) (r=0.341,p=0.002).Plasma TXB2 level was correlated with SBP (r=0.272,p=0.030),TC (r=0.363,p=0.003),and LDL-C (r=0.297,p=0.017). There were no correlation between blood pressure,blood lipids and FAPWV,ABI. No significant association was observed between the extent of lipid reduction and fall in CRPWV, FAPWV or plasma TXB2. CFPWV and plasma TXB2 level were positively correlated(r=0.303,p=0.016),while FAPWV and ABI were negatively correlated (r=-0.248,p=0.028).
5 The levels of alanine aminotransferase (ALT),total bilirubin (TBIL) and fasting blood sugar (FBS) were decreased evidently after therapy with Zhibitai for 8 weeks (P<0.05), but there were no significant alteration of them in Atorvastatin group (P>0.05).No significant changes of blood regulation and kidney function were found in two groups (P> 0.05).
6. In Atorvastatin group,one patient withdrew from the study because of the liver pain.The side effects of Zhibitai were very mild, and the compliance of patients was very well.
Conclusions:
1. Zhibitai capsule has the same effects on reducing serum levels of TG,TC and LDL-C as Atorvastatin after 8 week treatment.
2. Both Atorvastatin and Zhibitai can reduce the levels of FAPWV and CRPWV significantly, thus improving peripheral muscular medium-sized arterial elasticity,while ABI and CFPWV were not changed in the two groups.
3. The level of plasma TXB2 was reduced obviously in the two groups after 8 week treatment suggesting that platelet activation and the contraction of thromboxane A2 (TXA2) on vasvular system may be reduced to some extent.
4. Zhibitai may be effctive in treatment of abnormal liver function and lowering FBS.
5. Zhibitai capsule was relatively safe and the side effects were rare.
引文
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[43]Sainani GS,Maru VG. Role of endothelial cell dysfunction in essential hypertension[J] J Assoc Physicians India.2004;52:966-969.
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[1]周玉杰,葛均波,韩雅玲.防栓抗栓现代治疗策略[M].第1版.人民卫生出版社.2006,23
[2]赵玉林.血小板功能与心脑血管病[J].中华医学实践杂志.2005,4(3)
[3]Aviram M, Osamah Hussein, Mira Rosenblat. Interactions of platelets macrophages,and lipoproteins in hypercholesterolemia:An tiatherogenic effects of HMG-CoA reductase inhibitor therapy[J] .J Cardiovasc Pharmacol.1998,31 (1):39-45
[4]李家增,贺石林,王鸿利.血栓病学[M].第1版.北京科学出版社.1998.142-160.
[5]Relou IA, Hackeng CM, Akkerman JW, et al. Low-density lipoprotein and its effect on human blood platelets[J]. Cell Mol Life Sci 2003; 60:961-971.
[6]Clair RW. Pathogenesis of atherosclerosis [J]. Cardiology in Review.1997,5: 14-24.
[7]Laufs U, Gertz K,Dirnagl U,et al. Rosuvastatin, a new HMG-CoA reductase inhibitor, Upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice [J].Brain Res.2002,942(1-2):23-30.
[8]赵水平,李向平.他汀类药物治疗学[M].长沙：中南大学出版社.2005.95-103.
[9]林毅,陈新民,罗助荣,等.不同剂量阿托伐他汀对急性冠脉综合征患者炎症及血小板和纤溶活性的影响[J].中国全科医学.2007,13(1)：1060-1062.
[10]Laufs U, L a Fata V, L iao JK. Inhibition of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase [J]. J Bio 1 Chem.1997,272 (50):31725.
[11]Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase [J]. J Bio l Chem,1998,273 (37): 24266.
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