阿托伐他汀对糖耐量低减患者致动脉硬化因素的干预
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摘要
目的:颈动脉内-中膜厚度(IMT)是反映早期动脉硬化(AS)的敏感、可靠、无创的指标。探讨影响糖耐量低减(IGT)患者早期AS的危险因素及阿托伐他汀对其干预的机制。
方法:入选50例IGT患者及50例正常对照(NGT),分别为IGT组及NGT组。采用高分辨率多普勒超声检测两组颈动脉IMT及斑块形成情况。所有入选者均测量身高、体重、腰围、臀围、血压,测定空腹(FPG)及糖负荷后2 h血浆血糖(2hPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、高敏C反应蛋白(hs-CRP、)、一氧化氮(NO)。采用高频超声检测肱动脉血流介导的血管扩张功能(FMD),其指标用肱动脉舒张内径的变化率(D%)表示;并计算体重指数(BMI)、腰臀比(WHR)、胰岛素抵抗(IR)指数(HOMA-IR)。分析IGT组上述指标与颈动脉IMT的相关性及其独立的危险因素;针对IGT组给予阿托伐他汀20mg/日,服药3个月,观察服药前后上述指标的变化,分析颈动脉IMT的变化(△IMT)与其它指标变化的相关性。
结果:1.IGT组较NGT组BMI、WHR、2hPG、TG、LDL-C、hs-CRP、FINS、HOMA-IR、颈动脉IMT均明显增高,NO及D%明显减低,差别有统计学意义(P＜0.05,P＜0.01);两组间的年龄、性别、SBp、DBp、FPG、TC及HDL-C差别无统计学意义(P＞0.05)。2.IGT组颈动脉IMT与年龄、BMI、WHR、2hPG、TC、LDL-C、hs-CRP及HOMA-IR均呈正相关(P＜0.05,P＜0.01),与D%呈负相关(P＜0.01);而与SBp、DBp、FPG、TG、HDL-C、NO均无明显相关性(P＞0.05);经多元逐步回归,年龄、WHR、HOMA-IR及D%是颈动脉IMT的独立危险因素。3.服用阿托伐他汀3个月后,IGT组指标2hPG、TG、TC、LDL-C、hs-CRP及IMT均有显著下降,NO及D%显著升高,差别有统计学意义(P＜0.05,P＜0.01);而BMI、WHR、SBp、DBp、FPG、FINS、HDL-C及HOMA-IR差别无统计学意义(P＞0.05)。4.IGT组服药前后△IMT与△hs-CRP呈正相关(P＜0.05),与△D%呈负相关(P＜0.01):而与△TG、△TC、△LDL-C、△HDL-C、△FPG、△2hPG、△FINS、△HOMA-IR及△NO无明显相关性(P＞0.05)。
结论:IGT患者已经存在明显的早期AS及与之相关的多种危险因素,其中年龄、中心型肥胖、IR、内皮功能异常为其独立危险因素,是心脑等大血管疾病的高危人群;他汀类药物可通过调脂、抗炎、改善内皮功能及可能的改善IR、胰岛β-细胞功能等多种机制,防治IGT患者早期AS的发生发展。
Objective:Intima-media thickness(IMT)of carotid artery is a sensitive,reliable, and non-invasive index of early stage atherosclerosis.To determine the risk factor of early stage atherosclerosis in impaired glucose tolerance(IGT)patients and evaluate the interference mechanisms of atorvastatin with the risk factor of atherosclerosis in IGT patients.
Methods:One hundred patients were divided into 2 groups;experimental group (IGT,n=50)and control group(non IGT/NGT,n=50).Both groups underwent high-frequency Doppler echocardiography to evaluate IMT of carotid artery.Body height,body weight,waist line,hip line,blood pressure,fasting plasma glucose (FPG),two hours plasma glucose(2hPG),fasting insulin(FINS),triglyceride(TG), total cholesterol(TC),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),high sensitive C-reactive protein(hs-CRP),nitrogen monoxidum(NO),body mass index(BMI),waist-to-hip ratios(WHR),and insulin resistance index with homeostasis model(HOMA-IR)were measured in both groups. Flow-mediated diastolic function of brachial artery was examined using high-frequency echocardiography,which was indicated by diastolic inner diameter changing rate(D%).Analyze the association between those parameters and IMT of carotid artery in IGT group and that of independent risk factor.IGT group was administered by atorvastatin 20 mg/day for 3 months.All parameters were observed before and after drug administration.Analyze the correlation between the changes of carotid-IMT and the other parameters.
Results:(1)BMI,WHR,2hPG;TG,LDL-C,hs-CRP,FINS,HOMA-IR,IMT of carotid artery significantly increase in IGT group compared with those of the NGT group.Conversely,NO and D%significantly decrease in IGT group compared with those of the NGT group(P＜0.05,P＜0.01).No significant differences in age,sex, systolic BP,diastolic BP,FPG,TC and HDL-C between two groups(P＞0.05).(2) There was positive correlation between carotid-IMT and age,BMI,WHR,2hPG,TC, LDL-C,hs-CRP,HOMA-IR(P＜0.05,P＜0.01).Inversely,there was negative correlation between carotid-IMT with D%in IGT group(P＜0.01).However, carotid-IMT did not correlate with systolic BP,diastolic BP,FPG,TC and HDL-C, NO(P＞0.05).Linier regression analysis showed that age,WHR,HOMA-IR and D% are independent risk factors for carotid-IMT.(3).After 3-months of Atorvastatin treatment;2hPG,TG,TC,LDL-C,hs-CRP,IMT significantly decrease,NO and D% significantly increase(P＜0.05,P＜0.01)in IGT group.However,no significant differences were found in BMI,WHR,systolic BP,diastolic BP,FPG,FINS,HDL-C and HOMA-IR between before and after Atorvastatin treatment in IGT group (P＞0.05).(4)There was positive correlation between△IMT and△hs-CRP in IGT group,before and after treatment(P＜0.05).Negative correlation was found between△IMT and△D%(P＜0.01)and there was no correlation between△IMT and△TG,△TC,△LDL-C,△HDL-C,△FPG,△2hPG,△FINS,△HOMA-IR,△NO(P＞0.05).
Conclusions:IGT patients have already had risk factors of early stage atherosclerosis,including age,concentric obesity,IR,impaired endothelial function as independent risk factors of atherosclerosis that is to be a high risk factors in cardio-neuro-vascular diseases;Statin is considered to prevent and treat early stage atherosclerosis in IGT patients,through decreased lipid profile,anti-inflammation, improved endothelial function,ameliorate IR and insulinβ-cell function.
方法:入选50例IGT患者及50例正常对照(NGT),分别为IGT组及NGT组。采用高分辨率多普勒超声检测两组颈动脉IMT及斑块形成情况。所有入选者均测量身高、体重、腰围、臀围、血压,测定空腹(FPG)及糖负荷后2 h血浆血糖(2hPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、高敏C反应蛋白(hs-CRP、)、一氧化氮(NO)。采用高频超声检测肱动脉血流介导的血管扩张功能(FMD),其指标用肱动脉舒张内径的变化率(D%)表示;并计算体重指数(BMI)、腰臀比(WHR)、胰岛素抵抗(IR)指数(HOMA-IR)。分析IGT组上述指标与颈动脉IMT的相关性及其独立的危险因素;针对IGT组给予阿托伐他汀20mg/日,服药3个月,观察服药前后上述指标的变化,分析颈动脉IMT的变化(△IMT)与其它指标变化的相关性。
结果:1.IGT组较NGT组BMI、WHR、2hPG、TG、LDL-C、hs-CRP、FINS、HOMA-IR、颈动脉IMT均明显增高,NO及D%明显减低,差别有统计学意义(P＜0.05,P＜0.01);两组间的年龄、性别、SBp、DBp、FPG、TC及HDL-C差别无统计学意义(P＞0.05)。2.IGT组颈动脉IMT与年龄、BMI、WHR、2hPG、TC、LDL-C、hs-CRP及HOMA-IR均呈正相关(P＜0.05,P＜0.01),与D%呈负相关(P＜0.01);而与SBp、DBp、FPG、TG、HDL-C、NO均无明显相关性(P＞0.05);经多元逐步回归,年龄、WHR、HOMA-IR及D%是颈动脉IMT的独立危险因素。3.服用阿托伐他汀3个月后,IGT组指标2hPG、TG、TC、LDL-C、hs-CRP及IMT均有显著下降,NO及D%显著升高,差别有统计学意义(P＜0.05,P＜0.01);而BMI、WHR、SBp、DBp、FPG、FINS、HDL-C及HOMA-IR差别无统计学意义(P＞0.05)。4.IGT组服药前后△IMT与△hs-CRP呈正相关(P＜0.05),与△D%呈负相关(P＜0.01):而与△TG、△TC、△LDL-C、△HDL-C、△FPG、△2hPG、△FINS、△HOMA-IR及△NO无明显相关性(P＞0.05)。
结论:IGT患者已经存在明显的早期AS及与之相关的多种危险因素,其中年龄、中心型肥胖、IR、内皮功能异常为其独立危险因素,是心脑等大血管疾病的高危人群;他汀类药物可通过调脂、抗炎、改善内皮功能及可能的改善IR、胰岛β-细胞功能等多种机制,防治IGT患者早期AS的发生发展。
Objective:Intima-media thickness(IMT)of carotid artery is a sensitive,reliable, and non-invasive index of early stage atherosclerosis.To determine the risk factor of early stage atherosclerosis in impaired glucose tolerance(IGT)patients and evaluate the interference mechanisms of atorvastatin with the risk factor of atherosclerosis in IGT patients.
Methods:One hundred patients were divided into 2 groups;experimental group (IGT,n=50)and control group(non IGT/NGT,n=50).Both groups underwent high-frequency Doppler echocardiography to evaluate IMT of carotid artery.Body height,body weight,waist line,hip line,blood pressure,fasting plasma glucose (FPG),two hours plasma glucose(2hPG),fasting insulin(FINS),triglyceride(TG), total cholesterol(TC),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),high sensitive C-reactive protein(hs-CRP),nitrogen monoxidum(NO),body mass index(BMI),waist-to-hip ratios(WHR),and insulin resistance index with homeostasis model(HOMA-IR)were measured in both groups. Flow-mediated diastolic function of brachial artery was examined using high-frequency echocardiography,which was indicated by diastolic inner diameter changing rate(D%).Analyze the association between those parameters and IMT of carotid artery in IGT group and that of independent risk factor.IGT group was administered by atorvastatin 20 mg/day for 3 months.All parameters were observed before and after drug administration.Analyze the correlation between the changes of carotid-IMT and the other parameters.
Results:(1)BMI,WHR,2hPG;TG,LDL-C,hs-CRP,FINS,HOMA-IR,IMT of carotid artery significantly increase in IGT group compared with those of the NGT group.Conversely,NO and D%significantly decrease in IGT group compared with those of the NGT group(P＜0.05,P＜0.01).No significant differences in age,sex, systolic BP,diastolic BP,FPG,TC and HDL-C between two groups(P＞0.05).(2) There was positive correlation between carotid-IMT and age,BMI,WHR,2hPG,TC, LDL-C,hs-CRP,HOMA-IR(P＜0.05,P＜0.01).Inversely,there was negative correlation between carotid-IMT with D%in IGT group(P＜0.01).However, carotid-IMT did not correlate with systolic BP,diastolic BP,FPG,TC and HDL-C, NO(P＞0.05).Linier regression analysis showed that age,WHR,HOMA-IR and D% are independent risk factors for carotid-IMT.(3).After 3-months of Atorvastatin treatment;2hPG,TG,TC,LDL-C,hs-CRP,IMT significantly decrease,NO and D% significantly increase(P＜0.05,P＜0.01)in IGT group.However,no significant differences were found in BMI,WHR,systolic BP,diastolic BP,FPG,FINS,HDL-C and HOMA-IR between before and after Atorvastatin treatment in IGT group (P＞0.05).(4)There was positive correlation between△IMT and△hs-CRP in IGT group,before and after treatment(P＜0.05).Negative correlation was found between△IMT and△D%(P＜0.01)and there was no correlation between△IMT and△TG,△TC,△LDL-C,△HDL-C,△FPG,△2hPG,△FINS,△HOMA-IR,△NO(P＞0.05).
Conclusions:IGT patients have already had risk factors of early stage atherosclerosis,including age,concentric obesity,IR,impaired endothelial function as independent risk factors of atherosclerosis that is to be a high risk factors in cardio-neuro-vascular diseases;Statin is considered to prevent and treat early stage atherosclerosis in IGT patients,through decreased lipid profile,anti-inflammation, improved endothelial function,ameliorate IR and insulinβ-cell function.
引文
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