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Objective@#To analyze association of CYP2C19 genotype and platelet function phenotype and their impact on clinical outcomes including bleeding events of coronary artery disease(CAD) patients received clopidogrel post percutaneous coronary intervention(PCI).@*Methods@#Coronary atherosclerotic heart diseases patients underwent elective PCI and coronary stent implantation in Fuwai hospital were prospectively enrolled during May 2012 to April 2013. Patients were assigned into groups by genotype of CYP2C19 (extensive metabolizers, intermediate metabolizers, and poor metabolizers) and phenotype of platelet function (clopidogrel responders, semi-responders, and non-responders). The rates of major adverse cardiovascular events, combined cardiovascular events, and bleeding events were recorded during a at least 12 months follow-up period and compared among above defined groups. The association between genotype or phenotype and clinical outcome was assessed using multivariable Cox regression hazards model.@*Results@#Three hundred and eighty patients received coronary stent implantation and met the inclusion criteria of the study, including 157(41.3%) clopidogrel extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor metabolizers according to the genotype grouping; 98(25.8%) were responders to clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders according to the phenotype grouping. Three hundred and seventy-six patients accomplished follow-up. The highest combined cardiovascular events rate was observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers (15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the clopidogrel responders (33.7%(33/98)) as compared to the semi-responders (18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In multivariable Cox regression analysis, the adjusted risk of cardiovascular death, acute myocardial infarction, stent embolism, target lesion revascularization and angina onset was 2.305 times higher in clopidogrel poor metabolizers than in extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs. responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs. responders during the 12 months follow-up period.@*Conclusions@#Among CAD patients underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group carries a significantly higher risk for combined cardiovascular events than in extensive metabolizers group, while clopidogrel responders patients are at significantly higher risk for bleeding as compared to the semi-responders and non-responders.
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Objective: To analyze the relevant factors for combined use of low molecular weight heparin (LMWH) and statins causing transaminase elevation and to provide the reference for medication safety in clinical practice. Methods: There were 45 patients who received the combination of LMWH and statins treatment, then having ALT elevation in our ward from 2011-01 to 2012-12 were collected, by exclusion of patients with the history of high ALT at admission, interrupted treatment and incomplete record of liver function tests, a total of 32 patients were ifnally enrolled for investigation. The conditions for using LMWH and statins together, type of LMWH, timing of ALT elevation after medication and clinical outcomes were retrospectively analyzed. Results: All patients received statins including simvastatin, atorvastatin, rosuvastatin and pravastatin, and 15 patients took statins before using LMWH including enoxaparin, nadroparin and dalteparin. There were 18 patients had ALT increased below 3 times of the upper limit and 14 patients had ALT level ≥ 3 times of the upper limit, and ALT elevation occurred at the average of (3 ± 3.8) days after taking LMWH. All patients stopped using LMWH upon ALT elevation and 16 of them stopped taking statins. The ALT level gradually decreased to normal by application of hepatic-protective treatment in all patients.Conclusion: Combined using LMWH and statins could cause ALT elevation, LMWH and statins may have synergistic effect, and therefore, the enhanced monitor of liver function is necessary when using the combined medication.
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Objective: To describe the clinical characteristics with long-term prognosis in patients with mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHCM). Methods: A total of 66 MVOHCM patients treated in our hospital were retrospectively studied for their morbidity, clinical characteristics and mortality. The cumulative survival rate was calculated by Kaplan-Meier method; the risk factors for cardiac death and cardiovascular events were analyzed by uni- and multivariate Cox proportional hazard model. Results: There were 66 (2.74%) patients suffering from MVOHCM among 2413 patients of hypertrophic cardiomyopathy and the average diagnostic age was (40.16 ± 14.64) years. With (7.30 ± 6.25) years of follow-up study, the cardiovascular mortality was 13.6% and unexplained syncope (HR=13.37, 95% CI: 1.65-114.46, P=0.015) was the independent predictor for cardiovascular death. There were 45.45% (30/66) patients experienced at least 1 time of cardiovascular event and the most frequent one was non-sustained ventricular tachycardia (NSVT); 19.70% (13/66) of patients combined with apical aneurysms, and they were more inclined to experience NSVT. Conclusion: MVOHCM patients usually have unfavorable prognosis with the higher incidence of cardiovascular events, some patients may develop apical aneurysm. The early diagnosis of MVOHCM is important for appropriate treatment.
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<p><b>OBJECTIVE</b>To compare the clinical features and long-term outcome of patients with midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) and patients with apical hypertrophic cardiomyopathy (AHCM) in China.</p><p><b>METHODS</b>This retrospective study analyzed clinical data of 66 patients with MVOHCM and 263 patients with AHCM from a consecutive single-center cohort consisting of 2 413 patients with HCM. The clinical features, cardiovascular mortality and morbidity were compared between the two groups.</p><p><b>RESULTS</b>Compared with the AHCM, patients in the MVOHCM group was younger and more likely to be symptomatic over a mean follow-up of 7 years. The proportion of MVOHCM and AHCM were 2.7% (66/2 413) and 10.9% (263/2 413) (P < 0.001), respectively, in this cohort. Cardiovascular mortality of the two groups were 13.6% (9/66) and 0.8% (2/263) (P < 0.001), and cardiovascular morbidity of the two groups were 53.0% (35/66) and 14.4% (38/263) (P < 0.001).</p><p><b>CONCLUSION</b>MVOHCM is rarer, but the clinical manifestations and long-term outcomes are worse compared with AHCM in this patient cohort.</p>
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Humans , Cardiomyopathy, Hypertrophic , Retrospective StudiesABSTRACT
Objective: To explore the relationship between erythrocyte sedimentation rate (ESR) and myocardial infarction (MI) occurrence in patients with rheumatoid arthritis (RA) combining coronary artery disease (CAD). Methods: A total of 106 consecutive patients with RA combining CAD were studied. There were 46 male and 60 female patients and divided into 2 groups:RA with MI group, n=46 and RA without MI group, n=60. The base line condition was compared between 2 groups, and multivariate regression analysis was conducted to explore the risk factors for MI occurrence in relevant patients. Results: Compared with RA without MI group, RA with MI group had the lower level of cholesterol and higher levels of inlfammatory indexes of ESR, high sensitivity C-reactive protein (hs-CRP) and CRP, P0.05. Multivariate regression analysis indicated that ESR was the independent risk factor of MI occurrence, OR=1.024, 95%CI 1.024 (1.007-1.043), P=0.007. Conclusion: ESR was independently related to MI occurrence in patients with RA combining CAD.
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Objective: To study the effect of cytochrome P-450 4F2 (CYP4F2, rs2108622) gene polymorphisms in patients with warfarin for initial doses in 7 days. Methods: A total of 271 patients treated by warfarin were studied. The CYP4F2 gene polymorphisms were assessed by real-time PCR, the average initial warfarin doses in 7 days and the time of international normalized ratio (INR) ifrst arrived to therapeutic range were recorded. The differences of initial warfarin doses and the time of INR ifrst arrived to therapeutic range among CYP4F2 gene polymorphisms of CC, CT and TT genotypes were analyzed by statistical method. Results: The average initial warfarin doses among CYP4F2 polymorphisms of TT and CT/TT were higher than CC, P Conclusion: CYP4F2 polymorphisms inlfuenced the initial warfarin doses in 7 days in relevant patients.
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Objective: To compare the clinical characteristics and plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP) between the patients with hypertensive hypertrophic cardiomyopathy in elder age (HHCME) and the patients with hypertensive left ventricular hypertrophy (HTN-LVH). Methods: Our work included 2 groups, HHCME group,n=47 and HTN-LVH group,n=44. Duplex Doppler echocardiography was performed to determine left atrial diameter (LAd), left ventricular end-diastolic dimension (LVEDd), interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), velocity of early diastolic period (VE) and velocity of end-diastolic period (VA) in mitral valve oriifce. Plasma level of NT-proBNP was measured by ELISA. The above indexes were compared between 2 groups. Results:①Compared with HTN-LVH group, HHCME group presented decreased LVEDd and increased IVST, LVEF, allP0.05.②Plasma level of NT-proBNP was higher in HHCME group,P Conclusion: The plasma NT-proBNP level was higher in HHCME patients than that in HTN-LVH patients which indicated that HHCME patients may have worse prognosis. NT-proBNP might be helpful for differencing HHCME.
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<p><b>OBJECTIVES</b>To establish an algorithm to predict the warfarin maintenance dose in Chinese Han population and validate the accuracy of this algorithm.</p><p><b>METHODS</b>A total of 488 Chinese Han patients, hospitalized in Fuwai hospital and had a stable dose of warfarin and a target international normalized ratio (INR) of 1.5 to 3.0, were recruited. Indications for warfarin use included prosthetic heart valve, atrial fibrillation and pulmonary embolism. These patients were divided into derivation group (n = 323) and validation group (n = 165) according to the enrollment time. A warfarin maintenance dose algorithm was established based on genetic information, demographic characteristics and concomitant medications by multiple linear regression analysis in derivation group. In the validation group, we evaluated the accuracy of our algorithm by comparing the predicted dose with the actual dose.</p><p><b>RESULTS</b>Our algorithm included VKORC1-1639G > A, CYP2C9*3 and CYP4F2 genotype, age, Body hight, body weight, amiodarone and digoxin use (R(2) = 0.652, P < 0.001) .In the validation group, the average predicted dose by our algorithm had no statistical difference with the actual dose [(3.51 ± 1.03) mg vs. (3.53 ± 1.41) mg, P = 0.779]. Our algorithm identified 100 out of 165 (60.6%) patients in the validation group, whose predicted dose of warfarin was within 20% of the actual dose, and predicted warfarin dose was underestimated in 17.6% (29/165) patients and overestimated in 21.8% (36/165) patients.</p><p><b>CONCLUSION</b>Our algorithm based on VKORC1, CYP2C9 and CYP4F2 polymorphisms can help to predict the warfarin maintenance dose in Chinese Han Population.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Algorithms , Asian People , Genetics , China , Cytochrome P-450 CYP2C9 , Genetics , Cytochrome P-450 Enzyme System , Genetics , Cytochrome P450 Family 4 , International Normalized Ratio , Models, Theoretical , Polymorphism, Genetic , Vitamin K Epoxide Reductases , Genetics , Warfarin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms on Warfarin maintenance dose variation in Chinese Han Population.</p><p><b>METHODS</b>Four hundred eighty-eight patients with prosthetic heart valves, atrial fibrillation or pulmonary thromboembolism and achieved stable Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic characteristics, stable therapeutic dose of Warfarin and concomitant medications were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms, demographic characteristics and concomitant medications on Warfarin daily maintenance dose were analyzed with statistical method.</p><p><b>RESULTS</b>VKORC1 and CYP2C9 gene polymorphisms could explain more than 50% Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have a greater impact on Warfarin maintenance dose compared with demographic characteristics and concomitant medications.</p><p><b>CONCLUSION</b>VKORC1 and CYP2C9 gene polymorphisms have a significant impact on Warfarin maintenance dose in Chinese Han population.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Aryl Hydrocarbon Hydroxylases , Genetics , Asian People , Ethnology , Genetics , Atrial Fibrillation , Drug Therapy , Ethnology , Genetics , Cytochrome P-450 CYP2C9 , Cytochrome P-450 Enzyme System , Genetics , Cytochrome P450 Family 4 , Dose-Response Relationship, Drug , Epoxide Hydrolases , Genetics , Polymorphism, Single Nucleotide , Protein C , Genetics , Pulmonary Embolism , Drug Therapy , Ethnology , Genetics , Treatment Outcome , Vitamin K Epoxide Reductases , Genetics , WarfarinABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical features of statin-induced myopathy.</p><p><b>METHOD</b>The 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 to myopathy 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.</p><p><b>RESULTS</b>A 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 first medication and up to 4 years after medication. Observed clinical features were myalgia, 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). Percent 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 to 85 years) died because of ADR and all 4 cases received high-dose statin treatment, 3 of them suffered from complex combined diseases, acute disease progression and complex multiple drug use history.</p><p><b>CONCLUSIONS</b>Severe statin-induced myopathy, like rhabdomyolysis, is more likely to occur in old patients, in patients taking high-dose statin, especially simvastatin.</p>
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Aged , Female , Humans , Male , Middle Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscular Diseases , Myositis , Rhabdomyolysis , SimvastatinABSTRACT
<p><b>BACKGROUND</b>Whether two clopidogrel pretreatment strategies prior to elective percutaneous coronary intervention (PCI): a 300 mg loading dose (LD) in clopidogrel naїve patients and a 75 mg maintenance dose (MD) once daily in patients on chronic clopidogrel therapy play the same role in the platelet inhibition in Chinese with different CYP2C19 genotypes remains unknown. We aim to evaluate the impact on platelet inhibition by clopidogrel pretreatment strategy and its interaction effect with CYP2C19 genotype.</p><p><b>METHODS</b>Chinese patients undergoing PCI (n = 840) were assigned to 2×2 groups in the trial according to different clopidogrel pretreatment strategies (470 patients in LD, 370 patients in MD) and CYP2C19 genotypes (494 carriers of any CYP2C19 *2 or *3 loss-of-function allele, 346 non-carriers). The primary outcome was platelet aggregation (PA) as measured by the 10 µmol/L adenosine diphosphate induced light transmission aggregation.</p><p><b>RESULTS</b>Compared with MD group, LD strategy showed a significantly higher PA-((59.22 ± 11.67)% vs. (52.83 ± 12.17)%, P < 0.01), similar PA difference was observed in CYP2C19 loss-of-function carriers compared with non-carriers ((59.41 ± 10.91)% vs. (52.10 ± 12.90)%, P < 0.01). LD patients in either the CYP2C19 loss-of-function allele carrier or non-carrier group showed a significantly higher PA compared with MD group ((61.50 ± 10.61)% vs. (56.84 ± 10.74)%, P < 0.01; (56.06 ± 12.34)% vs. (46.88 ± 11.78)%, P < 0.01, respectively). A quantitative interaction effect was observed between clopidogrel pretreatment strategy and CYP2C19 genotype (P = 0.001).</p><p><b>CONCLUSION</b>The 300 mg LD strategy results in a decreased effect on platelet inhibition compared with the 75 mg MD in Chinese patients receiving clopidogrel prior to PCI, especially in the CYP2C19 2 or 3 loss-of-function allele non-carriers. (ClinicalTrials.gov number NCT01710436)</p>
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Aged , Female , Humans , Male , Middle Aged , Blood Platelets , Coronary Artery Disease , General Surgery , Cytochrome P-450 CYP2C19 , Genetics , Genotype , Percutaneous Coronary Intervention , Methods , Platelet Aggregation , Prospective Studies , Ticlopidine , Therapeutic UsesABSTRACT
@#Objective To evaluate the inhibition of urine 11-dH-TXB2 by dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin in Chinese cardiovascular patients after long-term therapy. Methods103 cardiovascular patients were treated with oral doses of dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin tablets (162 mg aspirin) daily for 24 weeks. The Urine 11-dH-TXB2 concentration were measured before and 6, 12, 24 weeks after administration. ResultsThe urine 11-dH-TXB2 concentration were （1840.41±1452.63） pg/ml, （820.01±610.55） pg/ml, （1011.19±1148.12） pg/ml, （1290.82±1425.51） pg/ml before and 6, 12, 24 weeks after administration. The urine 11-dh-TXB2 concentration was higher in 24th week than in 12th weeks and 6th week. ConclusionThe dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin can inhibit the platelet aggregation, which decreased after long-term administration.
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@#Objective To evaluate the inhibition of urine 11-dH-TXB2 by dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin in Chinese cardiovascular patients after long-term therapy. Methods103 cardiovascular patients were treated with oral doses of dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin tablets (162 mg aspirin) daily for 24 weeks. The Urine 11-dH-TXB2 concentration were measured before and 6, 12, 24 weeks after administration. ResultsThe urine 11-dH-TXB2 concentration were （1840.41±1452.63） pg/ml, （820.01±610.55） pg/ml, （1011.19±1148.12） pg/ml, （1290.82±1425.51） pg/ml before and 6, 12, 24 weeks after administration. The urine 11-dh-TXB2 concentration was higher in 24th week than in 12th weeks and 6th week. ConclusionThe dihydroxyaluminum aminoacetate-heavy magnesium carbonate-aspirin can inhibit the platelet aggregation, which decreased after long-term administration.
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OBJECTIVE:To provide references for improving the quality of clinical trial of new drug (phase I-IV),guaranteeing participants' interests and enhancing the core competitive power of drug clinical trial institutions. METHODS: The advantages of both the guiding principle of Good Clinical Practice(GCP) and the quality standards of ISO/IEC17025:2005 were applied throughout the quality control process of clinical drug trial. RESULTS & CONCLUSIONS: To establish quality management and supervision system in China that is in line with the international norm and national condition by combining GCP principle with the quality standards of ISO/IEC17025 is conducive to the improvement of the quality of clinical drug trial and enhancement of the core competitive power of drug clinical trial institutions in China.
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OBJECTIVE:To provide references for clinicians in the choice of antihypertensive drugs.METHODS:The antihypertensive efficacy 6 classes(or 15 kinds) of antihypertensive drugs in a monotherapy in the treatment of 370 patients with essential hypertension(EH) were compared.RESULTS:The blood pressure was effectively lowered by all of the antihypertensive drugs except doxazosin,and doxazosin and torasemide showed inferior efficacy in the reduction of diastolic blood pressure(DBP).CONCLUSION:Calcium antagonists with prolonged action,angiotensin converting enzyme inhibitor(ACEI),angiotens-in receptor antagonist,and the monotherapy of Terazosin or Indapamide can all effectively bring down the blood pressure.It is suggested that low-dose doxazosin and torasemide should not be used alone in treating essential hypertension.