9 Cardiovascular System

9 Cardiovascular System

2015066 Efficacy and safety com parison of different statins in elderly patients.CHEN Yahong（陳亞紅），etal.Dept Geriatrics，1st Hosp，Peking Univ，Beijing 100034.Chin JCardiol 2014；42（11）：910-915.

Ob jectiveTo compare the efficacy and safety of atorvastatin，rosuvastatin and Xuezhikang capsule in elderly.MethodsA total of 314 60-to-94-year-old（average（73.6±7.9）years old）patients who had been given different doses and types of statins were divided into three groups：the atorvastatin group（108 patients），the rosuvastatin group（104 patients）and the Xuezhikang capsule group（102 patients）.The serum TG，TC，LDL-C，HDL-C，ALT and CK were examined before and after the treatmentwhich lasted for at least4 weeks.All patientswere divided into moderate risk group（13，12 and 21 patients respectively in 3 groups）；high risk group（40，44 and 48 patients respectively in 3 groups）and very high risk group（55，48 and 33 patients respectively in 3 groups）according to guidelines on prevention and treatment of dyslipidemia in Chinese adults（2007 version）.The rate of reaching target goal and the dose when reaching target levels in different risk stratification groups were calculated and compared.ResultsSerum TC，LDL-C and non-HDL-C were significantly reduced after the 4-week-treatment in all the three groups（P＜0.01）.Serum LDL-C levels before and after treatment were（3.14±0.78）mmol/L vs.（2.14±0.65）mmol/ L in atorvastatin group（the arevage dose was（16.4± 4.8）mg/d），（2.93±0.77）mmol/L vs.（1.96± 0.55）mmol/L in rosuvastatin group（the arevage dose was（8.7±3.0）mg/d），and（2.70±0.62）mmol/L vs.（2.16±0.61）mmol/L in Xuezhikang capsule group（the arevage dose was（0.9±0.3）g/d）.Among all the three groups of patients，13，11 and 20 cases reached target levels of LDL-C in patients at moderate risk，38（95.0%），38（86.4%）and 40（83.3%）in patients at high risk，and 22（40.0%），30（62.5%）and 17（51.5%）in patients at very high risk.There were no statistical differences in the rate of reaching target levels of LDL-C，non-HDL-C and TC in the three groups and at different risks（P＞0.05）.One patient in the atorvastatin group showed ALT level elevation＞3times of the upper limit of normal value，there was no patient with CK level elevation＞5 times of the upper limit of normal value.ConclusionAtorvastatin，rosuvastatin and xuezhikang capsule at low dose and/or standard dose are effective and safe in elderly patients.

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2015067 Association between apolipoprotein A1-75 bp gene polymorphisms and risk for dyslipidem ia and coronary artery disease.WEIXuebiao（魏學(xué)標(biāo)），et al.Graduate Sch，South Med Univ，Guangzhou 510080.Chin JCardiol 2014；42（11）：916-921.

ObjectiveTo explore the relationship between the apolipoprotein ApoA1-75 bp polymorphism and risk for dyslipidemia and coronary artery disease（CAD）.M ethodsA total of 723 patients［mean age（62.4±10.2）years old］admitted to Guangdong General Hospital from 2011 to 2013 were enrolled.They were subdivided into CAD group（n=444）and non-CAD（n=279）group according to the result of coronary angiography（CAG）. Clinical data including the profiles of lipids，-75 bp gene polymorphisms and Gensini scores were analyzed to determine the correlation between-75 bp gene polymorphisms，lipid profile and CAD.ResultsFrequency of male gender，history of diabetes and smoking，TC，TG，LDL-C and ApoB level were significantly higher and HDL-C level was significantly lower in CAD group than in non-CAD group（all P＜0.05）.Frequency of A allele was significantly lower in CAD group than in non-CAD group（43.7%（194/444）vs.56.6%（158/279），P= 0.003）.The ApoA1-75 bp gene polymorphism was significantly correlated with CAD（P＜0.005）.Multivariate logistic regression analysis showed that-75 bp gene polymorphism mutation（OR=0.649，P=0.021）is an independent protective factor for coronary heart disease.ConclusionApoA1-75 bp gene polymorphism linkswith the risk for dyslipidemia and coronary artery disease.

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2015068 The anti-apoptosis effect and expression of m icroRNA-133a in rat myocardium of heart failure after myocardial in farction.LI Anying（李安瑩），et al.Dept Cardiol，3rd Xiangya Hosp，Centr South Univ，Changsha 410013.Chin J Arterioscler 2014；22（10）：1000-08.

Ob jectiveTo observe the anti-apoptosis effect and expression ofmicroRNA-133a（miR-133a）in ratmyocardium of heart failure after myocardial infarction（MI）.MethodsSprague-Dawley rats were divided into four groups random ly：①Sham group：rats were dealt with open-chest；②MIgroup：rats were operated by left anterior descending coronary artery ligation；③rAAV9 group：ratswere operated by leftanterior descending coronary artery ligation after transfected with rAAV9-Zs-Green by coronary injection；④miR-133a group：ratswere operated by left anterior descending coronary artery ligation after transfected with rAAV9-ZsGreen-pre-miR-133a by coronary injection.Fed for eightweeks，the ratswere tested the expressions ofmiR-133a and mRNA of transgelin-2（TAGLN2），Caspase-9 and Bcl-2 by real-time PCR，immunohistochemistry and Western blotwere used to determine protein level of TAGLN2，Caspase-9 and Bcl-2.Resu ltsThemiR-133a expression ofMIgroup decreased obviously compared with sham group（2.963±0. 461 vs.12.518±2.21）.ThemRNA and protein level of TAGLN2 and Caspase-9 both increased in MIgroup versus sham group，while Bcl-2 expression decreased in MI group.The expression ofmiR-133a was up-regulated after rAAV9-ZsGreen-pre-miR-133a coronary injection，the mRNA and protein level of TAGLN2 and Caspase-9 were reduced in the same group，while Bcl-2 expression increased.ConclusionThe down-regulation ofmiR-133a in failure heart after MI could decrease its degradation and inhibiting effects to TAGLN2 and Caspase-9，thus promote myocardial apoptosis.Myocardial apoptosismay be alleviated by over-expressedmiR-133a.

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2015069 Study on the m echanism of pravastatin changing polarity anti-inflammatory in murine macrophages.LIQuanzhong（李全忠），etal.Dept Cardiovasc，Affil Hosp，Guilin Med Coll，Guilin.541001. Chin JArterioscler 2014；22（10）：993-996.

ObjectiveTo investigate themechanism of statins to prevent and cure atherosclerosis（As）by the study of pravastatin sodium changes mouse macrophages polarity and anti-inflammatory action.M ethodsSupernatant from L929 cellswas used to inducemice bonemarrow cells in-to M0 macrophages，then itwas stimulated by LPS plus IFN-γ，and made into M1 macrophages，after that itwas given 50μmol/L pravastatin sodium，TLR4 specific receptor inhibitor for 12 h，then intervened with inhibition of 50μmol/L pravastatin sodium.ELISA was used to detect cells secretion factors，such as the level of IL-10 and IL-12.Flow cytometry was to detect the cell membrane surface antigen expression of CD16/32，CD206. Fluorescence quantitative polymerase chain reaction（PCR）was to detect the expression of TLR4，MyD88 and IRF5 mRNA.Resu ltsThe expression of IL-12，CD16/32 and TLR4，MyD88，IRF5 mRNA in M1 macrophages were increased，but the expression of IL-10，CD206 were higher，TLR4，MyD88，and IRF5 mRNA were lower in macrophages treated by pravastatin sodium（P＜0.05）.Compared with the 50μmol/L pravastatin sodium group，the effectof TLR4 specific receptor receptor inhibitor for 12 h，then interventing with inhibition of 50μmol/L pravastatin sodium group was not obvious（P＞0.05）.ConclusionPravastatin sodium can change macrophage polarity which plays a role of anti-in-flammatory.It may affect the TLR4-MyD88-IRF5 signaling transduction pathway，playing the effect of anti-As.

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2015070 Clinical analysis of 160 cases of statin-induced m yopathy.JIANG Yuexin（江岳鑫），et al.Key Lab，Clin Cardiovas Drug Trial Res，F(xiàn)uwai Hosp，CAMS&PUMC，Beijing 100037.Chin JCardiol 2014；42（11）：905-909.

Ob jectiveTo analyze the clinical features of statininducedmyopathy.MethodsThe statin-induced myopathy case reported as adverse drug reaction（ADR）to the Beijing Center for ADR Monitoring during January 2007 to December 2012 was summarized，patients were divided tomyopathy group and rhabdomyolysis group，according to the absence or presence of rhabdomylysis.The clinical characteristics，medication history and outcome were compared between the two groups.Resu ltsA total of 160 statin-induced myopathy cases（54 in rhabdomyolysis group（33.8%）and 106 cases in myopathy group（66.3%））were collected from the database［mean age：（64.22±13.55）years old，51.2%male，n=82］. The ADR occurred immediately after the firstmedication and up to4 yearsaftermedication.Observed clinical featuresweremyalgia，myositis，asymptommatic creatine kinase（CK）elevation or rhabdomyolysis.The average age were（68.54±15.41）years old in rhabdomylysis group and（62.02±12.41）years old in myopathy group（P= 0.004）.There was no gender difference between the rhabdomylysis group and myopathy group（P=0.406）. Twenty-four cases（44.4%）in rhabdomyolysis group and 26 cases（16.5%）in myopathy group were treated with high dose statin（P＜0.001）.The percentage of simvastatin treatment was significantly higher in rhabdomyolysis group（70.4%（38/54））than in myopathy group（32.1%（34/106），P＜0.001）.Spearman correlation analysis showed that age，high-dose statin treatment and simvastatin use were all positively correlated with rhabdomylysis（P＜0.001），and the correlation coefficients（r value）were 0.305，0.290 and 0.364，respectively.Four patients（aged from 71 to85 years）died because of ADR and all4 cases received high-dose statin treatment，3 of them suffered from complex combined diseases，acute disease progression and complexmultiple drug use history.ConclusionSevere statin-induced myopathy，like rhabdomyolysis，is more likely to occur in old patients，in patients taking high-dose statin，especially simvastatin.

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2015071 K indlin-2 regulates m igration and adhesion of vascu lar sm ooth m uscle cells viaβ1-integrin.WU Xiaolin（吳校林），et al.Dept Cardiol，Renmin Hosp，Wuhan Univ，Wuhan 430060.Chin J Cardiol 2014；42（11）：938-943.

ObjectiveTo explore the effects of Kindlin-2 RNA interference on vascular smooth muscle cells（VSMCs）migration，adhesion andβ1-integrin as well as the relationship between Kindlin-2 andβ1-integrin.M ethodsPrimary VSMCs were cultured，infected with Kindlin-2 siRNA lentiviral vectors.VSMCswere divided into three groups：the blank control group，the negative control group and the Kindlin-2 siRNA group.The ability of VSMCsmigration wasmeasured by Transwell experiment and wound healing assay.The ability of VSMCs adhesion to extracelluarmatrix was determined by cell-extracelluar matrix adhesion assay.The Kindlin-2 andβ1-integrinmRNA and protein expression levelswere detected by real-time quantitative PCR and Western blot.Totalβ1-integrin and activeβ1-integrin expression on the surface of VSMCswas evaluated by flow cytometry.ResultsThe efficiency of Kindlin-2 siRNA lentivirus infected VSMCs wasmore than 90%.The number of VSMCsmigration in the Kindlin-2 siRNA group was significantly lower than that of the blank control group and the negative group（all P＜0.05）.Moreover，the distance of VSMCsmigration was shorter than that of the blank control group and the negative group（all P＜0.05）.The number of VSMCs adhesion to collagenⅠwas less than that of the blank control group and the negative group（all P＜0.05）. A590nmof the Kindlin-2 siRNA group was also lower than that of the blank control group and the negative group（all P＜0.05）.Compared with the blank control group，the expression level of Kindlin-2 mRNA in the Kindlin-2 siRNA group decreased 47%（P＜0.05），but the expression level ofβ1-integrin mRNA remained unchanged.The Kindlin-2 protein level in the Kindlin-2 siRNA group was lower than that of the blank control group and the negative group（all P＜0.05）.β1-integrin protein levelwas similar among the three groups.Activatedβ1-integrin on the surface of VSMCs in the Kindlin-2 siRNA group was lower than that of the blank control group and the negative group（all P＜0.05）.However，the expression level of totalβ1-integrin on the VSMCs surface was similar among the three groups.ConclusionKindin-2 can regulate VSMCs migration and adhesion and activateβ1-integrin on the surface of VSMCs.

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2015072 Association between serum soluble CD146 level and p laque vu lnerability in carotid atherosclerosis.QIAN Yining（錢怡寧），et al.Dept Neurol，Beijing Anzhen Hosp，Capital Med Univ，Beijing 100029. Natl Med JChina 2014；94（43）：3392-96.

Ob jectiveTo explore the relationship between circulating level of soluble CD146（sCD146）and plaque vulnerability or inflammatory factors in patients with carotid atherosclerosis（CAS）.M ethodsForty CAS patients with carotid stenosis（≥70%）were enrolled and divided into 2 groups of stable and unstable plaque by ultrasonic imaging.And another 40 healthy subjects were enrolled for control group.Double-antibody sandwich enzyme-linked immunosorbent assay（ELISA）was employed tomeasure the serum levels of sCD146 andmatrix metalloproteinase-9（MMP-9），the correlation of sCD146 was analyzed with MMP-9 and high sensitivity CRP（hs-CRP），and whether sCD146 correlated with plaque vulnerability was evaluated.Resu ltsSoluble CD146 level was elevated in CAS patients versus healthy donors［（212±43）vs（173±36）ng/ml，P＜0.001］.And sCD146 level significantly increased in CAS patientswith unstable plaques than those with stable plaque［（218± 28）vs（176±25）ng/m l，P＜0.001］.And sCD146 was correlated with high-sensitivity C-reactive protein（hsCRP，r=0.370 9，P＜0.018 5），a well known marker for CAS inflammation.Also it was an independent risk factor for plaque vulnerability（OR=1.16，95% CI：1.020-1.310，P=0.019 2）.And its level was not correlated with the risk factors of CAS，such as age，homocysteine，triglyceride，total cholesterol（TC），low density lipoprotein-cholesterol（LDL-C）or high density lipoprotein-cholesterol（HDL-C）（P＞0.05）.But there was a good correlation with the serum level of MMP-9 in CAS patients（r=0.677 2，P＞0.001）.ConclusionThe concentration of soluble CD146 is positively correlated with hsCRP and MMP-9 in CAS patients.And inflammation and neovascularization may interactwith each other during atherosclerotic process.The serum level of sCD146 is correlated independently with plaque vulnerability.

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2015073 Effect of oxymatrine on myocardial cytosolic phospholipase A2，cyclooxygenase-1，cyclooxygenase-2 and prostacyclin synthase expression in rat w ith chronic heart failure.XU Yehua（徐燁華），et al.Ningxia Med Univ，Yinchuan 750004.Chin JArterioscler 2014；22（10）：973-979.

Ob jectiveThe present study was to investigate the protective of oxymatrine（OMT）on regulation of the expression of cytosolic phospholipase A2（cPLA2），cyclooxygenase-1（COX-1），COX-2 and prostacyclin synthase（PGIS）in isoproterenol-induced rat heart failure.M ethodsHeart failure was induced in Sprague-Dawley rats by 5 mg/kg isoproterenol（ISO）subcutaneous injec-tion for 7 days.The rats，maintained on a normal diet，were random ly divided into five groups given control，oxymatrine（100 mg/kg）alone，ISO and ISO with oxymatrine（100 mg/kg or 50 mg/kg）.In groups of ISO and ISO with oxymatrine（100 mg/kg or 50 mg/kg），saline or oxymatrine was administered orally for 7 days prior to the ISO administration.ISO（5 mg/kg）was administered subcutaneously for 7 days with saline or oxymatrine.In groups of control and oxymatrine（100 mg/kg）alone，saline was administered subcutaneously for 7 days.Serum brain natriuretic peptide（BNP）level，haemodynamic parameters，histopathological variables and expression of protein levelswere analyzed.ResultsOral administration of OMT significantly inhibited ISO-induced heart failure，as evaluated by serum BNP and haemodynamic parameters，and histological examinations.Coadministration of oxymatrine increased myocardial level of COX-2 and PGIS，and inhibited COX-1 expression in ISO-induced heart failure rat.Whereas the protein level for cPLA2 wasmarkedly increased by ISO，OMT exerted no effects on ISO-induced elevated protein cPLA2 expression.Compared with control group，and indexes in sham rats treated with OMT（100 mg/kg）alone were unaltered（all P＞0.05）.ConclusionOur results suggest that the favourable effects of oxymatrine formanagement of heart failure are probably achieved by regulation of the COX-1，COX-2 and PGIS expression.

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2015074 The effects of olm esartan on am bulatory b lood p ressures and b lood pressure variability in patientsw ith m ild to moderate essential hypertension.LI Jing（李菁），et al.Dept Cardiol，China-Japan Friendship Hosp，Beijing 100029.Chin J Intern Med 2014；53（10）：788-792.

ObjectiveTo evaluate the effectof olmesartanmedoxomil tablets（olmesartan）in comparison with Olmetec on 24 h ambulatory blood pressure（ABPM）and blood pressure variability（BPV）in patients with mild to moderate hypertension.M ethodsA randomized，doubleblind，double-mimic controlled trialwas performed.Forty-eight patients with mild to moderate essential hypertension were random ly into treatment group（olmesartan）and control group（Olmetec）for eightweeks.The ABPM was taken before and at the end of the trial.ResultsAfter eightweeks，treatmentwith olmesartan induced a significant reduction in ABPM in patients［（9±3）/（11± 3）mmHg（1 mmHg=0.133 kPa）］，which was similar with the reduction by Olmetec［（9±4）/（9±5）mm-Hg］，P＞0.05.This situation holds for BPV with the standard deviations of 24 h，systolic blood pressure/diastolic blood pressure of pre-treatment and pro-treatment were（10±2）/（11±3）mmHg vs（10±3）/（12±2）mmHg in olmesartan group，and（10±3）/（11±3）mmHg vs（12±3）/（12±4）mmHg in Olmetec group.（3）There is no difference in the rate ofadverse eventbetween olmesartan（10.42%）and Olmetec（8.33%）treatment（P＞0.05）.ConclusionSimilar to Olmetec，treatmentwith olmesartan once daily can significantly reduce ABPM in patients with mild to moderate essential hypertension.

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