Advancing cardiovascular outcomes with dapagliflozin and sacubitril in post-acute myocardial infarction heart failure and type 2 diabetes mellitus

Coronary heart disease and type 2 diabetes mellitus(T2DM)often co-occur,presenting substantial health risks,particularly following acute myocardial infarction(AMI).While percutaneous coronary intervention(PCI)is a prevalent treatment,complications such as microvascular dysfunction may lead to heart failure,necessitating additional therapies.This editorial examines the emerging roles of sacubitril/valsartan and sodium-glucose co-transporter 2 inhibitors in managing post-PCI.Recent research investigates the combined effects of dapag-liflozin and telmisartan on myocardial microperfusion in post-AMI heart failure patients with T2DM.The findings suggest that this combination enhances myo-cardial microcirculation,improves cardiac function,and achieves better glycemic control,with a reduced incidence of major adverse cardiovascular events.Despite ongoing challenges,the integration of dapagliflozin and sacubitril/valsartan re-presents a significant advancement in post-AMI care.Further investigation in larger cohorts and more diverse patient populations is required to confirm its long-term clinical outcomes.

Confounders of uric acid level for assessing cardiovascular outcomes

We read the article entitled Serum uric＇ acid as a prognostic marker in the setting of advanced vascular disease： a prospective study in the elderly by Stolfo, et al. with great interest. The authors evaluated the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. They founded meaningful association between SUA levels and of cardiovascular events and cancer related death. We believe that these findings will lead for further studies on uric acid.

Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors:A meta-analysis of cardiovascular outcome trials

BACKGROUND Dipeptidyl peptidase-4(DPP-4)inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus(T2DM).Recently,a series of large,randomized controlled trials(RCTs)addressing cardiovascular outcomes with DPP-4 inhibitors have been published.AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias.METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020.We extracted data concerning the following“hard”efficacy outcomes:fatal and non-fatal myocardial infarction,fatal and non-fatal stroke,hospitalization for heart failure,hospitalization for unstable angina,hospitalization for coronary revascularization and cardiovascular death.We also extracted data regarding the risk for major cardiac arrhythmias,such as atrial fibrillation,atrial flutter,ventricular fibrillation and ventricular tachycardia.RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo.DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction[risk ratio(RR)=1.02,95%CI:0.94-1.11,I2=0%],hospitalization for heart failure(RR=1.09,95%CI:0.92-1.29,I2=65%)and cardiovascular death(RR=1.02,95%CI:0.93-1.11,I2=0%).DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke(RR=0.96,95%CI:0.85-1.08,I2=0%)and coronary revascularization(RR=0.99,95%CI:0.90-1.09,I2=0%),Finally,DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina(RR=1.00,95%CI:0.85-1.18,I2=0%).As far as cardiac arrhythmias are concerned,DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation(RR=0.95,95%CI:0.78-1.17,I2=0%),while they were associated with a significant increase in the risk for atrial flutter,equal to 52%(RR=1.52,95%CI:1.03-2.24,I2=0%).DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias.CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM,while they do not seem to be associated with a significant risk for any major cardiac arrhythmias,except for atrial flutter.Therefore,this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors,except for those cases when newer antidiabetics(glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors)are not tolerated,contraindicated or not affordable for the patient.

Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.

Dual-chamber pacing confers better myocardial performance and improves clinical outcomes compared to single-chamber pacing

The deleterious effects of long term right ventricular pacing are increasingly being recognized today.Current clinical practice favors the implantation of dual-chamber permanent pacemaker which maintains atrioventricular synchrony and is associated with better quality of life.However,despite the popular belief and common sense surrounding the superiority of dual-chamber pacing over single chamber pacing,the same has never been conclusively verified in clinical trials.Some observational evidence however,does exists which supports the improved cardiac hemodynamics,lower the rate of atrial fibrillation,heart failure and stroke in dual-chamber pacing compared to single-chamber pacing.In the index study by Haque et al,right ventricular pacing,particularly in ventricular paced,ven-tricular sensed,inhibited response and rate responsive pacemaker adversely im-pacted the left ventricular functions over 9-months compared to dual pacing,dual sensing,dual responsive and rate responsive pacemaker.Although there are key limitations of this study,these findings does support a growing body of evidence reinstating the superiority of dual chamber pacing compared to single chamber pacing.

Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital

Background:Recent cardiovascular outcome trials(CVOTs)changed the therapeutic strategy of guidelines for type 2 diabetes.We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.Methods:This electronic medical record(EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1,2011,to June 30,2019.We identified patients meeting the inclusion criteria of a pragmatic randomized trial(EMPA-REG OUTCOME)based on EMRs and compared their baseline characteristics with those of the trial participants.The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.Results:We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389(17.4%)inpatients and 2646(7.2%)outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial.Compared with the trial population,the realworld inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age,blood pressure,and lipid profiles but comprised of fewer males,metformin users,anti-hypertensive drug users,and aspirin users,and had a lower body mass index.The group of outpatients meeting the eligibility criteria had fewer males,similar age,fewer metformin users,fewer insulin users,fewer anti-hypertensive drug users,and fewer aspirin users compared with the trial population.Conclusions:The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center.Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

DPP-4 inhibitors and GLP-1RAs:cardiovascular safety and benefits

Glucagon-like peptide-1 receptor agonists(GLP-1RAs)and dipeptidyl peptidase-4 inhibitors are commonly used treatments for patients with type 2 diabetes mellitus(T2DM).Both anti-diabetic treatments function by playing key modulatory roles in the incretin system.Though these drugs have been deemed effective in treating T2DM,the Food and Drug Administration(FDA)and some members of the scientific community have questioned the safety of these therapeutics relative to important cardiovascular endpoints.As a result,since 2008,the FDA has required all new drugs for glycemic control in T2DM patients to demonstrate cardiovascular safety.The present review article strives to assess the safety and benefits of incretin-based therapy,a new class of antidiabetic drug,on the health of patient cardiovascular systems.In the process,this review will also provide a physiological overview of the incretin system and how key components function in T2DM.

Cardiovascular sequelae in post-COVID-19 patients with moderate to severe CT severity score: A follow-up study

Objective:To study cardiovascular sequelae of post-COVID-19 patients with moderate to severe computed tomography(CT)severity score.Methods:A prospective,non-randomized,observational study was conducted on 100 post-COVID-19 patients with moderate to severe CT severity scores from January 2021 to December 2021.Fifty-nine were male[mean age(54.1±12.2)years]and 41 were female[mean age(46.9±15.1)years].Patients with previous cardiovascular disease,previous chronic lung disease,and pre-existing primary or secondary pulmonary hypertension were excluded.Patients were examined,and serial electrocardiogram and 2D echocardiography were performed to detect any cardiovascular abnormality.Results:Post-COVID-19 patients had persistent symptoms,the most common being fatigue(59%).Most of these symptoms were relieved on follow-up.A rise in systolic,diastolic blood pressure,and pulse rate was observed.The electrocardiographic evaluation revealed ST-T segment changes,sinus tachycardia,ventricular hypertrophy,and arrhythmias among a considerable number of patients.On echocardiography,left ventricular diastolic dysfunction was most common(43%).Pulmonary hypertension,as evidenced by elevated pulmonary artery systolic pressure,was seen in 15%of patients.Conclusions:The present findings reveal an increased incidence of cardiovascular complications after recovery from COVID-19 infection in those without pre-existing cardiovascular or chronic lung disease.

Pharmacoepidemiologic study of association between apparent treatment resistant hypertension, cardiovascular disease and interaction effect by sex and age

BACKGROUND A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension(aTRH)and risk of cardiovascular disease(CVD).AIM To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association.METHODS We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT).ALLHAT recruited participants(n=25516)from 625 primary care settings throughout the United States,Canada,Puerto Rico,and United States Virgin Islands,aged 55 and older with hypertension and at least one additional risk factor for heart disease.aTRH was assessed from the year 2 visit.CVD event was defined as one of the following from the year 2 follow-up visit:Fatal or non-fatal myocardial infarction,coronary revascularization,angina,stroke,heart failure,or peripheral artery disease.Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk.Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction.RESULTS Of the total study participants(n=25516),5030 experienced a CVD event during a mean of 4.7 years follow-up.aTRH was associated with a 30%increase in risk of CVD compared to non-aTRH[hazards ratio(HR)=1.3,95%CI:1.19-1.42].Sex and age modified this relationship on both multiplicative and additive scales independently.Stratified by sex,aTRH was associated with a 64%increase in risk of CVD(HR=1.64,95%CI:1.43–1.88)in women,and a 13%increase in risk of CVD(HR=1.13,95%CI:1.01–1.27)in men.Stratified by age,aTRH had a stronger impact on the risk of CVD in participants aged<65(HR=1.53,95%CI:1.32–1.77)than it did in those aged≥65(HR=1.18,95%CI:1.05–1.32).Significant two-way interactions of sex and aTRH,and age and aTRH on risk of CVD were observed(P<0.05).The observed joint effect of aTRH and ages≥65 years(HR=1.85,95%CI:1.22–2.48)in males was less than what was expected for both additive and multiplicative models(HR=4.10,95%CI:3.63–4.57 and 4.88,95%CI:3.66–6.31),although three-way interaction of sex,age,and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance(P>0.05).CONCLUSION aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age.Further studies are warranted to test these mechanisms.

Coronary artery disease and heart failure:Late-breaking trials presented at American Heart Association scientific session 2023

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure(HF).The dapagliflozin in patient with acute myocardial infarction(DAPA-MI)trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo,with no difference in cardiovascular outcomes.The MINT trial showed that in patients with acute MI and anemia(Hgb<10 g/dL),a liberal transfusion goal(Hgb≥10 g/dL)was not superior to a restrictive strategy(Hgb 7-8 g/dL)with respect to 30-day all-cause death and recurrent MI.The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy,percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure.The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist,placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year.The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given≥6 months after cardiac transplantation.Providing patients being treated for HF with reduced ejection fraction(HFrEF)with specific out-of-pocket(OOP)costs for multiple medication options at the time of the clinical encounter may reduce‘contingency planning’and increase the extent to which patients are taking the medications decided upon.The primary outcome,which was cost-informed decisionmaking,defined as the clinician or patient mentioning costs of HFrEF medication,occurred in 49%of encounters with the checklist only control group compared with 68%of encounters in the OOP cost group.

Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes

Both GLP-1 receptor agonists(GLP-1RA)and SGLT-2 inhibitors(SGLT-2I)are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure(SBP)modestly.Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c,body weight,and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects.Since several agents from each class of these drugs have shown an improvement in cardiovascular(CV)and renal outcomes in their respective cardiovascular outcome trials(CVOT),combination therapy is theoretically expected to have additional CV and renal benefits.In this comprehensive opinion review,we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone,although body weight lowering was nearly additive and the SBP lowering was more than additive.Our additional meta-analysis of CV outcomes with GLP1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone,against placebo.Interestingly,a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials.Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

Number of medications is associated with outcomes in the elderly patient with metabolic syndrome

Background The diagnosis of metabolic syndrome indicates a clustering of metabolic imbalances which in sum have been recognized as a major predictor of cardiovascular and all-cause mortality. The aim of this study was to assess the level of under-pharmacy and poly-pbarmacy and its prognostic impact in elderly patients with metabolic syndrome. Methods Retrospective chart-review at a tertiary medical center, of 324 patients greater than 65 years of age who met the International Diabetes Foundation criteria for metabolic syndrome diagnosis [Body Mass Index （BMI） 〉 30 kg/m2, diagnosis of type 2 diabetes, hypertension, and dyslipidemia]. Results There were 60 （18.5%） patients in the low （〈 5） medication burden group, 159 （49.1%） in the medium （〉 5 and 〈 10） medication burden group, and 105 （32.4%） in the high （〉 10） medication burden group. At baseline, the groups differed only by systolic blood pressure. At two years follow-up, the medium group had significantly better improvement in high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C）, HbAlc, and systolic blood pressure compared to the low medication burden group and significantly better improvement in triglycerides, Haemoglobin Alc （HbAlc） and systolic blood pressure compared to the high medication group. Decrease in HDL-C was the only variable associated with strokes. High medication burden predicted hospitalization burden. The number of anti-hypertensives, history of tobacco use, low and high medication burdens and decrease in HDL-C were all associated with death. Conclusions Both poly-pharmacy and under-pharmacy are associated with a decreased therapeutic benefit among patients with metabolic syndrome in terms of important laboratory measurements as well as clinical outcomes such as myocardial infarctions, hospitalization, and death.

Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.

Renin-angiotensin system blockers-SGLT2 inhibitorsmineralocorticoid receptor antagonists in diabetic kidney disease:A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease(DKD)have been tested in patients with type 2 diabetes mellitus(T2DM)in the past two decades.With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001,no other pharmacological agent tested in the past two decades have shown any clinically meaningful result.Recently,the sodium-glucose cotransporter-2 inhibitor(SGLT-2i),canagliflozin,has shown a significant reduction in the composite of hard renal and cardiovascular(CV)endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of reninangiotensin system blocker use.Another SGLT-2i,dapagliflozin,has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease(CKD),regardless of T2DM status.Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM.However,the full results of this trial have not yet been published.While the use of older steroidal mineralocorticoid receptor antagonists(MRAs)such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes,a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM,with reasonably acceptable side effects.

Relook at DPP-4 inhibitors in the era of SGLT-2 inhibitors

SGLT-2 inhibitors(SGLT-2Is)have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases,heart failure,and diabetic kidney disease.Similarly,GLP-1 receptor agonists(GLP-1RAs)have significantly improved atherosclerotic cardiovascular outcomes.To this end,DPP-4 inhibitors(DPP-4Is)are cardiac-neutral drugs.While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is,there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is.Moreover,the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions,unlike DPP-4Is.Furthermore,the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c(8.0%-8.5%)compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c(>8.5%-9.0%).These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.

Prognostic Significance of HbA1c Level in Asian Patients with Prediabetes and Coronary Artery Disease

Background:Measuring glycosylated hemoglobin(HbA1c)is a simple way to assess patients with prediabetes or diabetes mellitus.It has been shown that HbA1c level predicts prognosis in patients with coronary artery disease(CAD)and the incidence of diabetes mellitus.However,the prognostic significance of HbA1c level in Asian patients with prediabetes and CAD is not yet clear.Our study aimed to determine the relationship between HbA1c level and major adverse cardiovascular events(MACE)in patients with prediabetes and CAD.Methods:We enrolled 1367 patients with prediabetes and CAD in the final analysis,and grouped them according to the HbA1c level.Primary end points included nonfatal myocardial infarction,hospitalization for unstable angina,and ischemia-driven revascularization.Cox proportional-hazards regression analysis was used to determine the relation-ship between HbA1c level and MACE after our accounting for confounding factors.Results:A total of 1367 patients(age 58.8±10.3 years;71.6%men)were included.During 43 months of follow-up,197 patients experienced at least one primary end point event.Multivariate Cox proportional-hazards regression analy-sis showed in comparison of HbA1c levels that the hazard ratio for primary end points was 4.110,with a 95%confidence interval of 2.097-6.011(P<0.001).Conclusions:HbA1c level positively correlated with MACE,demonstrating it is a valuable indicator for indepen-dently predicting MACE in Asian patients with prediabetes and CAD.

Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

Sodium-glucose cotransporter-2 inhibitors(SGLT2 inhibitors)are a new type of drug for the treatment of diabetes,and they have been proven to have a good hypoglycemic effect.Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis,hospitalization for heart failure,cardiovascular death,and all-cause mortality and delay the progression of chronic kidney disease.Because of the protective effects of SGLT2 inhibitors on the heart and kidney,they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes.Therefore,it is necessary for cardiologists,patients with diabetes,and nephrologists to fully understand this type of drug.In this review,we summarize the following three aspects of SGLT2 inhibitors:the recent clinical evidence of their cardiovascular benefits,their mechanisms of action,and their safety.

Outcome and risk factors of early onset severe preeclampsia

Background Early onset severe preeclampsia is a specific type of severe preeclampsia, which causes high morbidity and mortality of both mothers and fetus. This study aimed to investigate the clinical definition, features, treatment, outcome and risk factors of early onset severe preeclampsia in Chinese women. Methods Four hundred and thirteen women with severe preeclampsia from June 2006 to June 2009 were divided into three groups according to the gestational age at the onset of preeclampsia as follows： group A （less than 32 weeks, 73 cases）, group B ,（between 32 and 34 weeks, 71 cases）, and group C （greater than 34 weeks, 269 cases）. The demographic characteristics of the subjects, complications, delivery modes and outcome of pregnancy were analyzed retrospectively. Results The systolic blood pressure at admission and the incidence of severe complications were significantly lower in group C than those in groups A and B, prolonged gestational weeks and days of hospitalization were significantly shorter in group C than those in groups A and B. Liver and kidney dysfunction, pleural and peritoneal effusion, placental abruption and postpartum hemorrhage were more likely to occur in group A compared with the other two groups. Twenty-four-hour urine protein levels at admission, intrauterine fetal death and days of hospitalization were risk factors that affected complications of severe preeclampsia. Gestational week at admission and delivery week were also risk factors that affected perinatal outcome. Conclusions Early onset severe preeclampsia should be defined as occurring before 34 weeks, and it is featured by more maternal complications and a worse perinatal prognosis compared with that defined as occurring after 34 weeks. Independent risk factors should be used to tailor the optimized individual treatment plan, to balance both maternal and neonatal safety.