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Impact of type 2 diabetes mellitus on the progression and revascularization of coronary non-target lesions in patients with coronary heart disease

Objective: To investigate the impact of type 2 diabetes mellitus on progression and revascularization of coronary non-target lesions in patients with coronary heart disease. Methods: From January 2010 to September 2014, we retrospectively analyzed the clinical data of patients with coronary heart disease who underwent two consecutive coronary angiographies at Fuwai Hospital. At least one coronary non-target lesion was recorded at the first procedure in these patients. Patients were grouped according to the diagnose of type 2 diabetes mellitus. Demographic features, risk factors of coronary heart disease, laboratory results as well as characteristics of coronary non-target lesions were collected at baseline (first coronary angiography) and follow-up (second coronary angiography). Lesion progression was defined by quantitative coronary angiography analysis. Lesions revascularization was recorded. Multivariable Cox regression analysis was used to define the impacts of diabetes mellitus on progression and revascularization of non-target lesions. Subgroup analysis in diabetic and non-diabetic groups were further performed. Receiver operating characteristics curve was used to identify the predictive value of HbA1c. Results: A total of 1 255 patients were included, and 1 003(79.9%) were male, age was(58.0±9.7) years old. And 486 patients were diagnosed with type 2 diabetes mellitus. Follow-up time was (14.8±4.5) months. Compared with non-diabetic group, diabetic group were older with less male and had higher BMI index as well as higher prevalence of hypertension, dyslipidemia, prior myocardial infarction and prior percutaneous coronary intervention(all P<0.05). Diabetic patients also had higher level of white blood cells, erythrocyte sedimentation rate, C-reactive protein, endothelin and HbA1c at both baseline and follow-up compared with non-diabetic patients (all P<0.01). There was no significant difference on progression of non-target lesions (20.0%(97/486) vs. 18.5%(142/769), P=0.512), revascularization of non-target lesions (13.2%(64/486) vs. 15.9%(122/769), P=0.190) and non-target lesion related myocardial infarction(1.9%(9/486) vs. 1.3%(10/769), P=0.436) between diabetic and non-diabetic patients. Multivariable Cox regression analysis revealed that diabetes mellitus was not an independent predictor for progression and revascularization of non-target lesions (Both P>0.05). Subgroup analysis in diabetic patients showed that baseline HbA1c level(HR=1.160, 95%CI 1.009-1.333, P=0.037) was an independent predictor for non-target lesion progression. Cut-off value of HbA1c was 6.5% (Area Under Curve(AUC) 0.57, specificity 88.7%; sensitivity 24.2%, P=0.046) by receiver operating characteristics curve. Patients with HbA1c level above 6.5% had 2.8 times higher risk of lesion progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion: Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.

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A cohort study on the association between resting heart rate and the risk of new-onset heart failure

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with β-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.

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Long-term outcomes of patients with ST-elevation myocardial infarction undergoing early versus late delayed percutaneous coronary intervention using drug-eluting stents

Objective: To compare the long-term outcomes in ST-elevation myocardial infarction (STEMI) patients who underwent early or late delayed percutaneous coronary intervention (PCI) using drug-eluting stents (DES). Methods: This study was a retrospective, observational and single-center study. Consecutive STEMI patients (n=977), who admitted to Fuwai Hospital in 2013 and underwent successful selective PCI using drug-eluting stents (DES) within 3 to 35 days after symptom onset were enrolled and divided into the early delayed PCI (3-14 d) group (n=495) and the late delayed PCI (15-35 d) group (n=482). General clinical data of the patients and related data of coronary angiography and interventional therapy were collected, and the endpoint events were followed up. The primary endpoint was 2-year major adverse cardiac and cerebrovascular events (MACCE) including cardiac death, recurrent myocardial infarction, definite or probable stent thrombosis and ischemic stroke. The secondary endpoint was 2-year ischemia-driven target vessel revascularization. The incidence of endpoint events of the two groups was compared, and it was compared again after the primary baseline characteristics such as age and gender were matched by the propensity scoring method at a 1∶1 ratio. Results: A total of 910 (93.1%) patients who underwent delayed PCI were transferred from other hospitals, and 292 (29.9%) patients received thrombolysis before PCI. The time interval before PCI was 14 (10, 20) days. The incidence of 2-year MACCE (3.0%(15/495) vs. 2.3%(11/482), P=0.468) and ischemia-driven target vessel revascularization (3.8%(19/495) vs. 5.0%(24/482), P=0.385) were similar between the two groups. The incidence of 2-year MACCE (3.3%(15/453 vs. 2.4%(11/453), P=0.426) and ischemia-driven target vessel revascularization (4.2% (19/453) vs. 4.9%(22/453), P=0.632) were also similar between the two groups after matching propensity score. Conclusion: The long-term clinical outcomes after early delayed PCI using DES is statistically equivalent to those of late delayed PCI using DES for STEMI patients who missed the time window for emergency PCI.

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Evaluating the long-term prognosis of coronary artery disease patients undergoing percutaneous coronary intervention by risk stratification with ACC/AHA classification of coronary lesions

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions: The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

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TanshinoneⅡA attenuates carotid artery atherosclerosis by deactivating mast cells in adventitia

Objective: To investigate the effects of tanshinone ⅡA on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E(-/-) mice model. Methods: Sixteen 8-week-old Apo E(-/-)male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E(-/-)+carboxymethyl cellulose per gavage) and the tanshinoneⅡA intervention group (Apo E(-/-)+30 mg/kg tanshinone ⅡA per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone ⅡA/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR. Results: After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneⅡA intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone ⅡA intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). TanshinoneⅡA intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05). Conclusions: Tanshinone ⅡA could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E(-/-) mice. The protective effect of tanshinoneⅡA is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.

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