Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study

Background Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. Methods In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of “compound reserpine and triamterene tablets (CRTTs)” for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. Results From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. Conclusions There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered;and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Tongmai Yangxin Pill combined with metoprolol or metoprolol alone for the treatment of symptomatic premature ventricular complex:a multicenter,randomized,parallel-controlled clinical study

OBJECTIVE To investigate the effects of Tongmai Yangxin Pill(TMYXP)combined with metoprolol tartrate or metoprolol alone for the treatment of premature ventricular complex(PVC)in patients with symptomatic frequent PVC.METHODS A total of 584 patients with symptomatic frequent PVC were randomly assigned(in a 1:1 ratio)into two groups:study group[n=292,TMYXP(40 pills twice/day,orally)combined with metoprolol tartrate(25 mg twice/day,orally)]and control group[n=292,metoprolol tartrate(25 mg twice/day,orally)plus placebo pill(40 pills twice/day,orally)].The total treatment period was eight weeks.RESULTS After eight weeks of treatment,the total effective rate of reduction of PVC in the study group and the control group were 76.4%and 51.4%,respectively(P<0.001).TMYXP combined with metoprolol tartrate demonstrated a significantly greater reduction of the frequency of PVCs compared with the metoprolol tartrate alone(−4537 times/24 h vs.−3013 times/24 h,P<0.001).The study group also showed a better result compared with the control group with respect to PVC related symptoms.In terms of New York Heart Association classification improvement,the total effective rates were 21.9%in the study group and 12.4%in the control group(P<0.05).Both the study group and the control group exhibited improvements in echocardiographic indexes.Left ventricular ejection fraction was significantly improved in the study group compared with the control group(P<0.05).There was no significant difference in the incidence of adverse events between the two groups.CONCLUSIONS Compared with metoprolol tartrate alone,TMYXP combined with metoprolol tartrate could more effectively reduce the frequency of PVC and alleviated PVC related symptoms,and improve cardiac function in patients with symptomatic PVC.

The relation between serum phosphorus levels and long-term mortality in Chinese patients with ST-segment elevation myocardial infarction

Background Elevated serum phosphorus levels may be associated with adverse outcomes in cardiovascular disease. This study aimed to investigate the relation between serum phosphorus levels and risk of all-cause mortality in Chinese patients with ST-segment elevation myocardial infarction (STEMI) who had preserved renal function at baseline. Methods We enrolled patients with STEMI who had preserved renal function at baseline in Xuanwu Hospital from January 2011 to December 2016. Those patients were divided into four groups based on serum phosphorus levels. All-cause mortality rates were compared between groups. Mean duration of follow up was 54.6 months. We used Cox proportional-hazards models to examine the relation between serum phosphorus levels and all-cause mortality after adjustment for potential confounders. Results 1989 patients were involved and 211 patients (10.6%) died during follow-up. Based on serum phosphorus levels, patients were categorized into the following groups:< 2.50 mg/dL (n = 89), 2.51–3.50 mg/dL (n = 1066), 3.51–4.50 mg/dL (n = 672) and > 4.50 mg/dL (n = 162), respectively. The lowest mortality occurred in patients with serum phosphorus levels between 2.51–3.50 mg/dL, with a multivariable-adjusted hazard ratio of 1.19 (95% CI: 0.64–1.54), 1.37 (95% CI: 1.22–1.74), and 1.46 (95% CI: 1.35–1.83) in patients with serum phosphorus levels of < 2.50 mg/dL, 3.51–4.50 mg/dL and > 4.50 mg/dL, respectively. Conclusions Elevated serum phosphorus levels were associated with all-cause mortality in Chinese patients with STEMI who had preserved renal function at baseline.

Study on possible synergistic anticancer cachexia effects of the main active compounds of Radix Sophorae flavescentis

Background:Cancer cachexia is a complex disease secondary to cancer,and no specific therapy for it has been found.The Chinese herb Kushen(Radix Sophorae flavescentis)is the dried root of Sophora flavescens Aiton,which has been widely applied in treating digestive and urinary inflammatory diseases.Matrine,one of the main components of Radix Sophorae flavescentis,can alleviate cancer cachexia.Methods:Compounds from Radix Sophorae flavescentis were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The targets related to cancer cachexia were queried from the Therapeutic Target Database(http://db.idrblab.net),DisGeNET database(http://www.disgenet.org),and Search Tool for Interacting Chemicals database,related literature,and constructed cancer cachexia-protein network.Cancer cachexia-protein network was merged with compound-protein networks respectively using Cytoscape software as well as network topology data and key targets counting.Pathway enrichment analysis was conducted via the Database for Functional Annotation Bioinformatics Microarray Analysis.Protein crystal structures and compound structures were queried from RCSB and PubChem databases,respectively.Molecular docking was conducted using Discovery Studio software.Results:The anticancer cachexia compounds of Radix Sophorae flavescentis were screened as oxymatrine,matrine,and kurarinol,and targets such as BIRC2,TNF and STAT3 were found.The mechanisms of oxymatrine,matrine,and kurarinol have the characteristics of synergy and complementarity.Kurarinol has a mechanism similar to that of matrine,which includes the FoxO signaling pathway,insulin resistance and mTOR signaling pathway.TNF signaling pathway is a common signaling pathway of kurarinol,oxymatrine and matrine.Adipocytokine signaling pathway is the other common pathway of kurarinol and oxymatrine except for the TNF signaling pathway.Kurarinol can be successfully docked with CYCS,GPX2,BIRC7,etc.,and kushenol C can be successfully docked with IKBKB and PIK3CD.Conclusion:Kurarinol,matrine,oxymatrine,and kushenol C may be the key compounds of Radix Sophorae flavescentis treating cancer cachexia.Additionally,TNF signaling pathway is the key pathway for the synergistic action of kurarinol,matrine and oxymatrine.

Association between serum uric acid level and endothelial dysfunction in elderly individuals with untreated mild hypertension

Background Endothelial dysfunction is the initial stage in atherosclerotic formation and progression and is associated with high serum uric acid(SUA)level.We hypothesized that reactive hyperemia index(RHI),which reflects endothelial function,is associated with SUA levels in elderly individuals with untreated mild hypertension.Methods We recruited 123 patients≥60 years with untreated mild hypertension.The association between SUA level and RHI was analyzed using univariate correlation analysis and multiple regression analysis.The receiver operating characteristic(ROC)curve was performed to validate the cutoff value of SUA that can be used to predict endothelial dysfunction.Results The serum uric acid level significantly increased in the RHI<1.67 group,and this result was still observed in the subgroup of men.RHI was inversely associated with SUA level(P=0.006)and the association was still observed after adjusting for factors,such as age,sex,smoking status,and creatinine level(P=0.014).In the subgroup analysis,a positive association was observed only in men.In the ROC curve analysis,the optimal cutoff values of SUA for predicting endothelial dysfunction was 293.5μmol/L in elderly mild hypertension patients and 287.0μmol/L in men.Conclusion A high SUA level was considered an independent predictor of endothelial dysfunction among elderly individuals,particularly men with untreated mild hypertension.