The Preliminary Exploration Of Metabolomics Of The Pathogenesis Of Coronary Heart Disease And The Clinical Study Of Optimizing The Interventional Treatment Of Coronary Heart Disease

UHPLC-Q-TOF/MS based plasma metabolomics reveals altered metabolic signatures in patients with coronary heart diseaseAim:Coronary heart disease(CHD)has been known bonded with complex metabolic disorders and its molecular etiology remains unclear.Using novel nontargeted metabolomics approach we explored the globle molecular perturbation profile of severe coronary heart disease compared with angiographically normal controls.Methods and Results:Blood samples of 150 CHD cases and 150 age-and gender-matched controls drawn from patients who underwent coronary angiography at FuWai Hospital between June 2011 and March 2015 were collected.Metabolic fingerprinting was performed by ultra high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry(UHPLC-QTOF/MS)technique.After adjusting for CHD traditional risk factors and metabolite batch using multiple linear regression models,levels of a comprehensive list of 105 metabolites were found significantly altered in CHD.Six novel metabolic signatures were discovered with strongest correlation with CHD risk after adjusting for multiple testing,out of which 4-Pyridoxic acid,Lithocholic acid and PG(20:3/2:0)were to our knowledge first reported.Conclusion:This study has surveyed the broad panel of nontargeted metabolites of CHD populations,revealing both novel and known associated metabolites and providing three potential novel targets for clinical prediction and a deeper insight into CHD pathogenesis.Evaluation of the effect of 4-pyridoxic acid on the proliferation of HUVEC and the production of inflammatory cytokines by THP-1 cellsAim:Our previous study discovered a novel metabolic signature,4-pyridoxic acid(4-PA),significantly elevated in the plasma of severe coronary heart disease(CHD)compared with angiographically normal controls using novel nontargeted metabolomics approach.We are also the first to confirm the positive association between plasma 4-PA and CHD risk(odds ratio,4.879;95%CI,(2.158,11.035);P=0.0002).We hypothesized that elevated 4-PA may promote atherogenesis by affecting the normal function human umbilical vein endothelial cell(HUVEC)and human monocytic cell line(THP-1).Methods and Results:To test this hypothesis,we analyzed the proliferation of HUVEC and the production of inflammatory cytokines by THP-1 cells under the stimulation of 4-PA.We used the NaOH solution(0.1mL lmol/L)as the solvent to prepare the 4-PA solution and added into the cell culture medium.We tested 7 different concentrations during 4 time points in proliferation evaluation of HUVEC.The results showed that 4-PA started to inhibit HUVEC proliferation from the time point of 48h and the growth curves continual declined to the lowest at 2000 nmol/L(up to 10.56%).We tested 6 different concentrations of 4-PA at 48h stimulation on IL-1β/TNF-α/ICAM mRNA expression by qRT-PCR assay.Results showed that 4-PA has no impact on inflammatory cytokines expression by THP-1 cells on the concentration less than 1000 nmol/L.The expression of IL-1β mRNA,TNF-a mRNA and ICAM mRNA were significantly up-regulated at the concentration of 1000 nmol/L and 2000 nmol/L(P<0.05),which the maximum is up to 1.22 fold,1.4 fold and 1.74 fold separately higher than control.Conclusion:The present study demonstrates that 4-PA inhibits HUVEC proliferation and enhances inflammatory responses of THP-1 cells which play important roles in atherosclerosis progression.Can "Hybrid stent implantation" improve long-term safety without adversely affecting efficacy when treating multilesion coronary artery disease in the drug-eluting stent era?Background:Though drug-eluting stent(DES)almost solved problem of restenosis,safety issues related to stent thrombosis are still the major concern of DES.We hypothesized that hybrid stent implantation may decrease the use of DES,probably improving the long-term safety but not affecting efficacy adversely when treating mutilesion coronary artery disease in the DES era.Methods:From April 2004 to October 2006,848 patients with multilesion disease underwent hybrid stent implantation.During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital.According to propensity score matching,we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study.We obtained the 24-month clinical outcome including death,myocardial infarction(MI),thrombosis,target lesion revascularization(TLR),target vessel revascularization(TVR),and major adverse cardiac events(MACE,the composite of death,MI,and TVR).We used Cox’s proportional-hazard models to assess relative risks of all the outcome measures after propensity match.Results:At 24 months,patients in the hybrid stent implantation group showed a significantly higher risk of TLR(8.39%vs.3.28%,HR 2.38,95%CI:1.50-3.70),TVR(11.07%vs.6.32%,HR 1.61,95%CI:1.15-2.27)and MACE(13.75%vs.8.75%,HR 1.37,95%CI:1.02-1.85).No significant difference was apparent in terms of mortality(1.22%vs.1.70%,HR 0.55,95%CI:0.24-1.25)MI(1.95%vs.2.31%,HR 0.73,95%CI:0.37-1.42),or thrombosis(definite+probable)(0.73%vs.1.58%,HR 0.40,95%CI:0.15-1.05).Conclusion:In patients with multilesion coronary artery disease,the exclusive DES implantation was associated with significantly lower risks of TLR,TVR and MACE,and the hybrid stent implantation did not result in any significant improvements regarding safety issues.Prospective studies are needed to confirm our results.Risk Stratification of Periprocedural Myocardial Infarction after Percutaneous Coronary Intervention:Analysis Based on the SCAI DefinitionObjectives:Few large-sample studies have attempted to predict the risk of SCAI-defined PMI.To investigate the predictors of and generate a risk prediction method for periprocedural myocardial infarction(PMI)after percutaneous coronary intervention(PCI)using the new PMI definition proposed by the Society for Cardiovascular Angiography and Interventions(SCAI).Methods:A total of 3,371 patients(3,516 selective PCIs)were included in this single-center retrospective analysis.The diagnostic criteria for PMI were set according to the SCAI definition.All clinical characteristics,coronary angiography findings and PCI procedural factors were collected.Multivariate logistic regression analysis was performed to identify independent predictors of PMI.To evaluate the risk of PMI,a multivariable risk score(PMI score)was constructed with incremental weights attributed to each component variable according to their estimated coefficients.Results:PMI occurred in 108(3.1%)of all patients.Age,multivessel treatment,at least one bifurcation treatment and total treated lesion length were independent predictors of SCAI-defined PMI.PMI scores ranged from 0 to 20.The C-statistic of PMI score was 0.71(95%confidence interval:0.66-0.76).PMI rates increased significantly from 1.96%in the non-high-risk group(PMI score<10)to 6.26%in the high-risk group(PMI score≥10)(P<0.001).Conclusions:Age,multivessel treatment,at least one bifurcation treatment,and total treated lesion length are predictive of PMI.The PMI score could help identify patients at high risk of PMI after PCI.