A Series Of Studies On The Clinical Significance Of Abnormal Glucose And Lipid Metabolism

Objectives:Previous studies have shown that both triglyceride glucose(TyG)and haemoglobin glycation indexes(HGI)are predictors of cardiovascular risk.However,the prognostic value of TyG index and HGI in patients with type 2 diabetes mellitus(T2DM)and stable coronary artery disease(CAD)is not determined.Methods:From April 2011 to October 2014,we consecutively enrolled 1579 patients with T2DM who had angina-like chest pain and scheduled for coronary angiography.The baseline clinical characters and laboratory measurements for these patients were collected.We conducted a nested case-control study among 1282 T2DM patients with stable CAD.Patients were followed up for 3846 person-years.Endpoints were defined as major adverse cardiovascular events(MACEs),which included cardiovascular mortality,non-fatal myocardial infarction(MI),stroke,post-discharge revascularization[percutaneous coronary intervention(PCI)and coronary artery bypass grafting(CABG)].A total of 160 patients with events(12.5%)were identified and matched individually on age,gender,previous use of lipid lowering agents and duration of follow-up with 640 controls.TyG index was calculated as In[fasting triglycerides(mg/dL)*fasting plasma glucose(FPG,mg/dL)/2].HGI was assessed according to the linear relationship between FPG and hemoglobin A1c(HbA1c)as HbA1c(%)-0.012*FPG(mg/dL)-5.175.Multivariate Cox regression analyses and Kaplan-Meier curves were performed to estimate the association between TyG index and HGI with MACEs.Results:Among the 160 patients with MACEs,20(12.5%)died,26(16.3%)had stroke,17(10.6%)developed non-fatal MI,73(45.6%)underwent unplanned PCI or CABG and 24(15.0%)had hospitalized unstable angina.Compared with non-event group(n=640),the event group had significantly higher levels of TyG and HGI.In Kaplan-Meier analysis,the upper tertiles of TyG index and HGI had a significant lower event-free survival(p=0.002;p=0.036,respectively).Of the note,both TyG index and HGI were associated with increased risk of MACEs after adjusting for confounding risk factors including age,sex,body mass index,hypertension,family history of CAD,smoke,high density lipoprotein cholesterol(HDL-C),non-HDL-C,creatinine,uric acid,high sensitive C reactive protein,and coronary severity score[adjusted HR(95%CI):1.693(1.238-2.316);1.215(1.046-1.411),respectively].Moreover,adding TyG index to the Cox model increased the C-statistic to 0.638(95%CI:0.595-0.683,p=002)while the C-statistic was not statistically improved when HGI was included(p=0.240).Conclusions:Both TyG index and HGI could predict cardiovascular outcomes in T2DM patients with new-onset,stable CAD while TyG index might be better.Objective:The aim of the present study is to examine the effects of free fatty acids(FFAs)on major cardiovascular events(MACEs)in patients with stable coronary artery disease(CAD)and different glucose metabolism status.Methods:In this study,we consecutively enrolled 5443 patients with stable CAD from March 201 1 to May 2015.The baseline clinical characters and laboratory measurements for these patients were collected.CAD was diagnosed as coronary stenosis≥50%of at least one coronary artery.Patients were categorized into 9 groups according to both status of glucose metabolism status[diabetes mellitus(DM),pre-diabetes(Pre-DM),normal glycaemia regulation(NGR)]according to guideline of American Diabetes Association and FFAs levels(low,medium and high with cut-off value 0.3 and 0.5mmol/L).Plasma levels of FFAs were determined by automated biochemistry analyzer.All subjects were followed up for the occurrence of the MACEs.Endpoints were defined as major adverse cardiovascular and cerebrovascular events,which included cardiovascular mortality,non-fatal myocardial infarction(MI),stroke,post-discharge revascularization(percutaneous coronary intervention and coronary artery bypass grafting).Kaplan-Meier curves and Cox regression analyses and were performed to estimate the association between FFAs levels and glucose metabolism status with MACEs.Results:During a median of 6.7 years’ follow-up,608 MACEs occurred,including 155 deaths,71 nonfatal MI,209 nonfatal strokes and 173 unplanned revascularizations.DM but not Pre-DM patients had significantly higher levels of FFAs than NGR population[median(interquartile range):DM:0.46(0.35-0.57)mmol/L,Pre-DM:0.40(0.29-0.49)mmol/L,NGR:0.40(0.30-0.48)mmol/L].A two-fold higher FFAs level was independently associated with MACEs after adjusting for confounding factors including age,sex,body mass index,hypertension,family history of CAD,smoke,high density lipoprotein cholesterol,low density lipoprotein cholesterol,triglyceride,left ventricle ejection fraction,Gensini score and baseline statins[Hazard Ratio(HR):1.242,95%confidence interval(CI):1.084-1.424,p-value=0.002].Adding FFAs to the Cox model increased the C-statistic by 0.015(0.005-0.027).No significant difference inMACEs was observed between NGR and Pre-DM groups(P>0.05).When patients were categorized by both status of glucose metabolism and FFAs levels,medium and high FFAs were associated with significantly higher risk of MACEs in Pre-DM[1.736(1.018-2.959)and 1.779(1.012-3.126),all p-value<0.05]and DM[2.017(1.164-3.494)and 2.795(1.619-4.824),all p-value<0.05].Conclusions:The present data indicated that baseline FFAs levels were associated with the prognosis in DM and Pre-DM patients with CAD,suggesting that FFAs may be a valuable predictor in patients with impaired glucose metabolism.Objectives:Elevation in small dense low-density lipoprotein(sdLDL)is common in patients with diabetes mellitus(DM),which has already been reported to be associated with incidence of coronary artery disease(CAD).The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM.Methods:A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events(MACEs)up to 8.5 years.CAD was diagnosed by angiography and clinical and laboratory data were recorded at baseline.Te MACEs were defned as cardiovascular mortality,non-fatal myocardial infarction(MI),stroke,unplanned percutaneous coronary intervention(PCI)or coronary artery bypass grafting(CABG),and hospitalized unstable angina.Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer.The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism[DM,Pre-DM,normal glycaemia regulation(NGR)]was evaluated.Kaplan-Meier curves and Cox regression analyses and were performed to estimate the association between FFAs levels and glucose metabolism status with MACEs.Results:A total of 464(11.2%)MACEs were documented(70 cardiovascular deaths,49 sufered nonfatal MI,108 had non-fatal strokes and 158 received unplanned revascularization and 79 suffered hospitalized unstable angina).Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile.both DM and Pre-DM groups had higher levels of plasma sdLDL than NGR group,but no significant difference existed between DM and Pre-DM.When the prognostic value of high sdLDL was assessed in different glucose metabolism status,the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors(hazard ratio:1.83,95%confident interval:1.24-2.70,p<0.05).However,no significant association was observed for high sdLDL plus Pre-DM or NGR.Conclusions:The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD,suggesting that sdLDL may be useful for CAD risk stratification in DM.Objectives:Previous study has indicated that lipoprotein(a)[Lp(a)]is an independent predictor of atherosclerotic cardiovascular disease(CVD).Current guidelines highlighted the necessity of measuring Lp(a)in patients with intermediate or high risk of CVD,familial hypercholesterolemia,or family history of premature CVD.However,no study is currently available regarding the prognosis of Lp(a)in patients with coronary artery disease and impaired glucose metabolism.The aim of the present study is to determine the effects of elevated Lp(a)on cardiovascular events(CVEs)in patients with stable CAD under different glucose metabolism status.Methods:In this multicenter study,we consecutively enrolled 5143 patients from March 2011 to February 2015.The baseline clinical characters and laboratory measurements for these patients were collected.CAD was diagnosed as coronary stenosis≥50%of at least one coronary artery.Lp(a)was determined by immunoturbidimetry method.prediabetes mellitus(Pre-DM)and diabetes mellitus(DM)were defined according to the criteria of American Diabetes Association.Patients were categorized according to status of glucose metabolism[DM,Pre-DM,normal glycaemia regulation(NGR)]levels and further classified into 12 groups by Lp(a)levels(<10mg/dL,10≤Lp(a)<30mg/dL,30≤Lp(a)<50m/dL,Lp(a≥50mg/dL).CVE endpoints included nonfatal acute myocardial infarction(MI),stroke and cardiovascular mortality.Trained nurses or physicians completed the interview.Multivariate Cox regression analyses and Kaplan-Meier curves were performed to estimate the association between Lp(a)levels,glucose metabolism status,and CVEs.Results:Among 5,143 subjects,18.8%,43.5%,and 37.6%were diagnosed as having NGR,pre-DM,and DM,respectively,according to ADA criteria.During a median of 6.1 years’follow-up,435(8.5%)CVEs occurred(154 died,76 suffered nonfatal MI,and 205 had nonfatal strokes).The prevalence of CVEs in the NGR,pre-DM,and DM groups was 5.8%,7.7%,and 10.7%,respectively.Kaplan-Meier curves indicated that no significant difference in occurrence of CVEs was observed between NGR and Pre-DM groups while DM patients presented significantly higher risk of CVEs.ByLp(a)status,Lp(a)≥50mg/dL were least likely to be free of events.When status of glucose metabolism was incorporated in stratifying factors,30≤Lp(a)<50mg/dL and Lp(a)≥50mg/dL was associated with significantly higher risk of subsequent CVEs in Pre-DM[2.181(1.099-4.327)and 2.668(1.383-5.415),all p<0.05]and DM[3.088(1.535-5.895)and 3.470(1.801-6.686),all p<0.05].Moreover,adding Lp(a)to the Cox model increased the C-statistic by 0.022(0.003-0.046,p=0.043)and 0.029(0.013-0.048,p=0.001)in Pre-DM and DM respectively while the C-statistic was not statistically improved when Lp(a)was included for CVEs prediction in NGR.Conclusions:Our findings,for the first time,indicated that elevated Lp(a)levels might affect the prognosis in Pre-DM patients with stable CAD,suggesting that Lp(a)may help further stratify stable CAD patients with mild impaired glucose metabolism.