Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease / 中华医学杂志(英文版)

BACKGROUND@#Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD.@*METHODS@#This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations.@*RESULTS@#TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs . 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs . 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44-3.39, P <0.001; HR: 3.32, 95% CI: 1.30-8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10-3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75-2.90, P = 0.257).@*CONCLUSION@#RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.

Analysis of revascularization strategies for elderly patients with ST-segment elevation myocardial infarction and multivessel disease / 中华老年医学杂志

Objective:To compare the effects of staged percutaneous coronary intervention(PCI)after emergency PCI and emergency culprit-only PCI on clinical outcomes of elderly patients with ST-segment elevation myocardial infarction(STEMI)and multivessel disease.Methods:A retrospective analysis was performed on 389 elderly patients with STEMI and multivessel lesions, aged ≥70 years and within 12 h of onset, admitted to the Clinical College of Thoracic Medicine, Tianjin Medical University, between January 2014 and September 2019.According to different revascularization strategies, enrolled patients were divided into the culprit-only PCI group(79.18%, 308)and the staged PCI group(20.82%, 81). Kaplan-Meier analysis and the Cox proportional hazards regression model were used to compare the incidences of major adverse cardiac and cerebrovascular events(MACCE), all-cause death, cardiac death, recurrent myocardial infarction, stroke and ischemia-driven revascularization between the two groups and to evaluate the effects of different revascularization strategies on MACCE and all-cause death.Then subgroup analysis was performed.Results:During a 56-month follow-up, 131 patients developed MACCE and 96 patients died.Compared with the culprit-only PCI group, the staged PCI group had a lower risk of MACCE( HR: 0.404, 95% CI: 0.227-0.716, P=0.002), all-cause death( HR: 0.354, 95% CI: 0.171-0.730, P=0.005), cardiac death( HR: 0.363, 95% CI: 0.157-0.838, P=0.018), and recurrent myocardial infarction( HR: 0.229, 95% CI: 0.055-0.953, P=0.043). There was no significant difference in the incidence of stroke or ischemia-driven revascularization between the two groups( P>0.05). The reduced risk with staged PCI for MACCE and for all-cause mortality persisted in all subgroups.Multivariate Cox proportional hazards regression revealed that, after adjusting for confounding factors, staged PCI was an independent protective factor for MACCE( HR: 0.44, 95% CI: 0.239-0.815, P=0.009)and for all-cause death( HR: 0.390, 95% CI: 0.90, P=0.020). Conclusion:Compared with culprit-only PCI, staged PCI can significantly improve the long-term prognosis of elderly patients ≥70 years with STEMI and multivessel disease within 12 h of onset.

miR-509-3p promotes oxidized low-density lipoprotein-induced apoptosis in mouse aortic endothelial cells / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of microRNA-509-3p (miR-509-3p) on the apoptosis of atherosclerotic vascular endothelial cells.@*METHODS@#Mouse aortic endothelial cells (MAECs) were divided into normal control group, oxidized low-density lipoprotein (ox-LDL) group, miR-509-3p overexpression group, miR-509-3p overexpression control group, miR-509-3p inhibitor + ox-LDL group, and miR-509-3p inhibitor control + ox-LDL group. MAEC were induced with 100 mg/L ox-LDL for 24 hours, and then transfected with miR-509-3p overexpression/inhibitor and corresponding control for 48 hours. The miR-509-3p expression in MAECs exposed to ox-LDL was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Flow cytometry was used to detect the level of apoptosis, and cell counting kit (CCK-8) was used to detect the proliferation activity of MAECs. The direct gene targets of miR-509-3p were predicted using bioinformatics analyses and confirmed using a dual luciferase reporter assay. The expression of Bcl-2 mRNA and protein was detected by RT-qPCR and Western blotting, respectively.@*RESULTS@#Compared with the normal control group, miR-509-3p was significantly upregulated in ox-LDL-stimulated MAECs (1.68±0.85 vs. 1.00±0.30, t = 2.398, P < 0.05). After transfection of MAECs with miR-509-3p overexpression, the luciferase activity of the BCL2 3'UTR WT reporter gene was significantly lower than that of miR-509-3p overexpression control group (0.83±0.06 vs. 1.00±0.07, t = 4.531, P = 0.001). The luciferase activity of the BCL2 3'-UTR mutant (MUT) reporter gene was not significantly different from that of miR-509-3p overexpression control group (0.94±0.05 vs. 1.00±0.08, t = 1.414, P = 0.188). Compared with the normal control group and miR-509-3p mimics control group, the cell proliferation activity was decreased [(0.60±0.06)% vs. (1.00±0.09)%, (0.89±0.04)%, both P < 0.01], the percentage of apoptotic cells were increased [(23.46±2.02)% vs. (7.66±1.52)%, (10.40±0.78)%, both P < 0.05], and the mRNA and protein expression of Bcl-2 were significantly downregulated (Bcl-2 mRNA: 0.52±0.13 vs. 1.00±0.36, 1.10±0.19, Bcl-2 protein: 0.42±0.07 vs. 1.00±0.11, 0.93±0.10, both P < 0.01) in miR-509-3p overexpression group. Compared with the ox-LDL group, inhibition of miR-509-3p expression could increase the proliferation activity of MAECs induced by ox-LDL [(0.64±0.35)% vs. (0.34±0.20%)%, P < 0.05], and reduce the apoptosis rate [(13.59±2.22)% vs. (29.84±5.19)%, P < 0.01], and up-regulated the expression of Bcl-2 mRNA and protein in MAECs induced by ox-LDL (Bcl-2 mRNA relative expression: 0.82±0.09 vs. 0.52±0.10, Bcl-2 protein relative expression: 0.83±0.17 vs. 0.40±0.07, both P < 0.05).@*CONCLUSIONS@#Bcl-2 was one of the target genes of miR-509-3p. miR-509-3p can reduce the proliferation activity of endothelial cells, reduce the expression of Bcl-2, and promote cell apoptosis, thereby promoting the occurrence and development of atherosclerosis. Inhibition of miR-509-3p expression may be a potential therapeutic target for atherosclerosis.

Expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome and their significance / 中华危重病急救医学

Objective To investigate the expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance. Methods A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were associated with STEMI. Results Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×109/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×109/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×109/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4+CD45RO+ T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4+CD45RO+ T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4+CD45RA+ T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4+CD45RA+ T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4+CD45RO+ T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003). Conclusions There was no significant difference in the ratio of CD4+CD45RA+ T cells among UAP, NSTEMI and STEMI patients, and CD4+CD45RO+ T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4+CD45RO+ T cells ratio may be risk factor of STEMI.

PCSK9 monoclonal antibody reduces serum level of lipoprotein(a) :Recent study advances / 中华老年医学杂志

Lipoprotein (a)[Lp(a)] is the independent risk tactors tor arteriosclerotic cardiovascular disease(ASCVD).Lp (a) combined with traditional risk factors can increase accurate prediction of the risk for ASCVD.The serum Lp(a)level is correlated with multiple-vessel disease,coronary artery plaque load,vulnerable plaque and in-stent restenosis.Lp(a)is related with coronary artery calcification,calcified aortic stenosis and heart failure.Therefore,Lp(a)level is an independent risk factor for cardiovascular events in ASCVD patients.The proprotein convertase subtilisin/kexin type 9 (PCSK9)monoclonal antibody can decrease the levels of low-density lipoprotein cholesterol and Lp(a),and further reduce the residual risk of major adverse cardiovascular events in ASCAD patients on the basis of statin therapy.

Expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome and their significance / 中华危重病急救医学

Objective@#To investigate the expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance.@*Methods@#A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were associated with STEMI.@*Results@#Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×109/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×109/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×109/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4+CD45RO+ T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4+CD45RO+ T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4+CD45RA+ T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4+CD45RA+ T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4+CD45RO+ T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003).@*Conclusions@#There was no significant difference in the ratio of CD4+CD45RA+ T cells among UAP, NSTEMI and STEMI patients, and CD4+CD45RO+ T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4+CD45RO+ T cells ratio may be risk factor of STEMI.

PCSK9 monoclonal antibody reduces serum level of lipoprotein(a): Recent study advances / 中华老年医学杂志

Lipoprotein(a)[Lp(a)]is the independent risk factors for arteriosclerotic cardiovascular disease(ASCVD). Lp(a)combined with traditional risk factors can increase accurate prediction of the risk for ASCVD.The serum Lp(a)level is correlated with multiple-vessel disease, coronary artery plaque load, vulnerable plaque and in-stent restenosis.Lp(a)is related with coronary artery calcification, calcified aortic stenosis and heart failure.Therefore, Lp(a)level is an independent risk factor for cardiovascular events in ASCVD patients.The proprotein convertase subtilisin/kexin type 9(PCSK9)monoclonal antibody can decrease the levels of low-density lipoprotein cholesterol and Lp(a), and further reduce the residual risk of major adverse cardiovascular events in ASCAD patients on the basis of statin therapy.

Application of non-invasive ventilator in acute heart failure with preserved ejection fraction / 中华急诊医学杂志

Objective To investigate the clinical features of patients with heart failure and the safety and efficacy of noninvasive ventilator in patients with heart failure.Methods Sequentially enrolled 65 patients who were diagnosed with decompensated heart failure in Tianjin Chest Hospital Heart Center from October 2016 to October 2017 and who had acute heart failure during hospitalization requiring noninvasive ventilator,were divided into the HF-PEF group (n=19) and HF-REF group (n=46).The clinical data of the two groups and the observation indexes before and after the application of the non-invasive ventilator were compared.Results Comparing the admission data of the two groups,the proportion of patients with hypertension (57.9％ vs 21.7％,P=0.005) and LVEF(％) (53.00±4.85 vs 33.07±7.24,P＜0.01)were significantly higher in the HF-PEF group than those in the HF-REF group;LVEDD (mm) in the HFPEF group was significantly lower than that in the HF-REF group (50.00±5.23 vs 63.82±8.95,P＜0.01).In the two groups of patients with acute left heart failure,blood lactate levels (mmol/L) in the HF-PEF group (4.20±1.06 vs 2.02±0.88,P＜0.05) and systolic blood pressure (mmHg) (151.32±43.40 vs 117.90± 19.55,P＜0.05) were significantly higher than those in the HF-REF group.After the application of non-invasive ventilator,systolic blood pressure (mmHg) (34.38±9.36 vs 16.94±5.19,P=0.038) and PaCO2 (mmHg)(2.49±0.98 vs-0.06±0.00,P=0.025),and lactic acid (mmol/L) (2.06±0.67 vs 0.04±0.01,P=0.001) were significantly lower in the HF-PEF group than those in the HF-REF group.While the NT-proBNP level (ng/L) (13 064.90±1 963.83 vs 11 687.13±1 028.03,P=0.848) did not decrease significantly,and the time of non-invasive ventilator application (h)was significantly longer than that in the HF-REF group (152.74±10.61 vs 71.03±10.41,P=0.013).Conclusions Hypertension is the main cause of HF-PEF group.The systolic blood pressure and blood lactate level in HF-PEF patients with acute left heart failure are significantly higher than HF-REF patients.Non-invasive ventilator is also safe and effective for the treatment of acute left heart failure in HF-PEF patients,but HF-PEF patients with acute left heart failure have a longer clinical remission time.

Relationship between serum levels of osteoproteins, inflammatory cytokines and coronary heart disease and disease severity / 中华危重病急救医学

Objective To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity. Methods The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD. Results A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. ① Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (μg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (μg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (μg/L):298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (μg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L):64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). ② The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (μg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (μg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05).③ Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. ④ ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 μg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 μg/L, the sensitivity was 69.7%, the specificity was 95.7%. Conclusions CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.

Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease / 中华危重病急救医学

Objective To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-κB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). Methods 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. Results All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD. Conclusions The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.

Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease / 中华危重病急救医学

OBJECTIVE@#To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD).@*METHODS@#528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD.@*RESULTS@#All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD.@*CONCLUSIONS@#The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.

Investigation of relationship between mean platelet volume and saphenous vein graft restenosis after coronary artery bypass grafting / 中华老年医学杂志

Objective To investigate the relationship between mean platelet volume(MPV)and saphenous vein graft restenosis in patients receiving coronary artery bypass grafting(CABG),and to analyze the clinical significance of MPV in the prediction of restenosis after CABG.Methods A total of 354 patients admitted into Tianjin chest hospital from September 2009 to September 2014 with suspected myocardial ischemic events 3 to 5 years after CABG treatment was enrolled for a retrospective analysis.According to the coronary angiography(CAG)results,patients were divided into the vein bridge vascular lesion group(saphenous vein graft diseases,SVGD)(n=233)and the venous bridge vascular patency group(saphenous vein graft,SVG)(n=121).Paired t test was used to analyze the relationship between different factors and the bridge vascular patency.The binary logistic regression was used to analyze the effects of MPV and other factors on bridge vascular patency.Venous bridge stenosis ＞ 50％ was considered to be clinically significant and to damage myocardial blood supply.Results The MPV was higher in the SVGD group than the SVG group [(10.2±1.5)fl vs.(9.6±1.5)fl,P＜0.01].The logistic regression analysis showed that MPV(OR =1.268,95％CI:1.053-1.570,P=0.014),age(OR =1.007,95％CI:1.038-1.117,P=0.000),gender (OR=0.452,95％CI:0.250-0.816,P=0.008),diabetes mellitus(OR=2.319,95％CI:1.221-4.405,P =0.010)were the independent risk factors for venous bridge stenosis in the two groups,gender(OR=0.495,95％CI:0.251-0.976,P=0.042),diabetes mellitus(OR =2.237,95％CI:1.105-4.527,P =0.025),MPV(OR=1.334,95％CI;1.050 1.694,P=0.018),fibrinogen(OR=1.654,95％CI:1.020-2.682,P =0.041)were the independent risk factors for venous bridge stenosis in non-elderly patients,and age(OR =1.178,95％CI:1.116-1.244,P =1.178)was an independent risk factor for vein graft stenosis in elderly patients.The restenosis rate was higher in patients with MPV ≥ 12 fl(92.6％ or 25/27) than in the patients with MPV ＜ 12 fl(63.6％ or 208/327).The receiver operating characteristics(ROC) curve showed that the areas under the curve of MPV,age,gender,diabetes,fibrinogen were 0.610,0.657,0.394,0.626,0.654,respectively,and the area under the curve of joint diagnosis was 0.796,showing that joint prediction value was higher than any single prediction value(P＜0.01).Conclusions MPV level is an independent risk factor for vein graft stenosis,and has higher predictive value in combination with age,gender,diabetes and fibrinogen.

Association of MMP3 promoter 5A/6A polymorphism with stability of extracellular matrix of atherosclerotic plaque / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of 5A/6A polymorphism in the promoter region of MMP3 gene with the stability of extracellular matrix of atherosclerotic plaque.@*METHODS@#Clinical data of 776 consecutive patients undergoing percutaneous coronary intervention (PCI) was reviewed. MMP3 gene polymorphisms and serum level of MMP3 for the second admission were collected. The target gene fragment containing MMP3 promoter region was transfected into HepG2 vector cells. The influence of the polymorphism on the expression of the MMP3 gene was determined in vitro.@*RESULTS@#Compared with the first admission data, the proportion of mutant MMP3 genotypes (5A/5A+5A/6A) was significantly higher in patients with acute myocardial infarction (AMI) compared with the control group (37.6% vs. 24.9%, P<0.01). 64.1% of the patients carrying the 5A allele had AMI, whereas only 50.11% of those carrying the 6A allele had AMI (P<0.01). The proportion of wild-type MMP3 genotype (6A/6A) was significantly higher in the stenotic group compared with the non-restenosis group (79.5% vs. 66.5%, P<0.01). Restenosis has occurred in 9.5% of patients harboring the 5A allele compared with 16.2% in those carrying the 6A allele (P<0.01). In addition, serum level of MMP3 in the restenosis group was significantly lower than that of the non-restenosis group (P<0.01). In vitro studies confirmed that the expression of pGL2-Basic/6A was significantly lower than that of pGL2-Basic/5A.@*CONCLUSION@#The 5A/6A polymorphism in the promoter region of the MMP3 gene may influence its transcriptional activity and impact on the degradation or push-up of extracellular matrix, resulting in a difference in the stability of atherosclerosis plaques, which in turn may induce different pathological processes in AMI or restenosis after stenting.

A meta-analysis on the association between genetic polymorphisms of osteoprotegerin and cardiovascular disease / 中华心血管病杂志

Objective@#To explore the association between genetic polymorphisms of rs2073617T/C (950T/C) and rs2073618G/C(1181G/C) in the osteoprotegerin gene and cardiovascular disease with meta-analysis.@*Methods@#A computer-based search for the study of relationship between genetic polymorphisms of rs2073617T/C and rs2073618G/C in the osteoprotegerin gene and cardiovascular disease were performed in electronic databases including China National Knowledge Infrastructure(CNKI), China Biomedical Literature Database, Wanfang Database, Chinese Journal Full-text Database, Embase, PubMed, and Cochrane Library, supplemented by manual search, from the beginning of library to February 28, 2017. The quality of the included studies were assessed by the Newcastle-Ottawa Scale (NOS) scoring system. Data were analyzed using STATA 12.0 software.@*Results@#Eleven clinical case-control studies that enrolled 2 115 patients with cardiovascular disease and 1 467 healthy subjects were included.The results indicated that osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C might be closely associated with the susceptibility to cardiovascular disease(rs2073617T/C allele model: OR=0.79, 95%CI 0.73-0.87, P=0.001;rs2073618G/C M allele and W allele: OR=0.83, 95%CI 0.74-0.92, P=0.001). The osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C were significantly related to the incidence of coronary artery disease and acute coronary syndrome(coronary artery disease allele model: OR=0.83, 95%CI 0.75-0.92, P=0.001; acute coronary syndrome allele model: OR=0.73, 95%CI 0.62-0.85, P<0.001). However, there was no significant correlation between the genetic polymorphisms of these two sites and the lesion vessel number of coronary artery (rs2073617T/C allele model:OR=1.00, 95%CI 0.81-1.24, P=0.985;rs2073618G/C allele model:OR=0.98, 95%CI 0.80-1.21, P=0.626). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-ligase detection reaction(PCR-LDR) evidenced the association between osteoprotegerin gene polymorphisms and cardiovascular disease(allele model: OR=0.79, 95%CI 0.72-0.86, P<0.001), but no obvious relationship was found with fluorogenic quantitative detection and molecularprobe(allele model: OR=0.86, 95%CI 0.65-1.12, P=0.263).@*Conclusion@#This meta-analysis indicates that the osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C may be closely related to the increased risk of cardiovascular disease.

Predictors and effect of repeat revascularization in elderly CHD patients with DM after coronary drug-eluting stent implantation / 中华老年心脑血管病杂志

Objective To analyze the incidence and predictors of unplanned repeat revascularization (RR) in CHD patients with DM within 2 years after coronary drug-eluting stent (DES) implantation.Methods A total of 2764 CHD patients with DM who underwent successful DES were divided into RR group (n=383) and non-RR group (n=2381).The effect of RR on all-cause mortality and myocardial infarction (MI) was analyzed by Cox regression analysis.Results Unplanned RR was detected in 383 patients (13.9％) within 2 years after DES.The rate of insulin therapy for DM was higher and the duration of DM was longer in RR group than in non-RR group (P＜0.05,P＜0.01).Multivariate Cox regression analysis showed that insulin therapy for DM,history of coronary artery bypass graft,serum HbAlc and LDL-C level,multivessel PCI and no use of statins during the follow-up period were the independent predictors of RR.RR was related with MI (adjusted HR=3.967,95％CI:1.284-6.254,P=0.017) but not related with all-cause mortality (adjusted HR=6.134,95％CI:0.435-26.224,P=0.154).Conclusion The severity of disease,complex coronary artery procedures and insufficient drug therapy are the risk factors for RR,and RR is related with ischemic cardiovascular events.

Analysis of clinical characteristics and survival status of patients with non-vaIvular atrial fibrillation complicated with type 2 diabetes mellitus / 重庆医学

Objective To investigate the clinical characteristics of patients with non-vaIvular atrial fibrillation (NVAF) combined with type 2 diabetes mellitus (T2DM),and explore the effect of T2DM on survival status of patients with NVAF.Methods A total of 646 patients with NVAF in Tianjin Chest Hospital from January 2014 to September 2015 were enrolled in the study,and were divided into T2DM group (n=110) and non-T2DM group (n=536) according to whether these patients were complicated with T2DM.The clinical data,incidence rates of cerebral infarction and cardiovascular death after 1-year follow-up were compared between the two groups.Multivariate Cox regression analysis was performed to determine independent factors for cerebral infarction and cardiovascular death within 1 year.Results The age,body mass index,incidence rates of hypertension,coronary heart disease,transient ischemic attack (TIA) or stroke,and hyperlipidemia,and application rates of aspirin,statins in the T2DM group were higher than those in the non-T2DM group,there were statistically significant differences (P＜0.05).After 1-year follow-up,the incidence rate of cardiovascular death in the T2DM group was 14.5 ％ which was significantly higher than 5.1％ in the nonT2DM group (P＜0.05).The incidence rate of cerebral infarction within 1 year in the T2DM group and non-T2DM group were 12.7 ％ and 6.4％,respectively.There was no significant difference in the incidence rate between the two groups (P＞0.05).Multivariate Cox regression analysis showed that age,TIA or stroke history and T2DM were the independent risk factors for cerebral infarction (P＜0.05).Age,heart failure and T2DM were the independent risk factors for cardiovascular death,and ACEI/ARB was an independent protective factor (P＜0.05).Conclusion T2DM could increase the risk for cerebral infarction and cardiovascular death in patients with NVAF.

Analysis of clinical characteristics and survival status of patients with non-vaIvular atrial fibrillation complicated with type 2 diabetes mellitus / 重庆医学

Objective To investigate the clinical characteristics of patients with non-vaIvular atrial fibrillation (NVAF) combined with type 2 diabetes mellitus (T2DM),and explore the effect of T2DM on survival status of patients with NVAF.Methods A total of 646 patients with NVAF in Tianjin Chest Hospital from January 2014 to September 2015 were enrolled in the study,and were divided into T2DM group (n=110) and non-T2DM group (n=536) according to whether these patients were complicated with T2DM.The clinical data,incidence rates of cerebral infarction and cardiovascular death after 1-year follow-up were compared between the two groups.Multivariate Cox regression analysis was performed to determine independent factors for cerebral infarction and cardiovascular death within 1 year.Results The age,body mass index,incidence rates of hypertension,coronary heart disease,transient ischemic attack (TIA) or stroke,and hyperlipidemia,and application rates of aspirin,statins in the T2DM group were higher than those in the non-T2DM group,there were statistically significant differences (P＜0.05).After 1-year follow-up,the incidence rate of cardiovascular death in the T2DM group was 14.5 ％ which was significantly higher than 5.1％ in the nonT2DM group (P＜0.05).The incidence rate of cerebral infarction within 1 year in the T2DM group and non-T2DM group were 12.7 ％ and 6.4％,respectively.There was no significant difference in the incidence rate between the two groups (P＞0.05).Multivariate Cox regression analysis showed that age,TIA or stroke history and T2DM were the independent risk factors for cerebral infarction (P＜0.05).Age,heart failure and T2DM were the independent risk factors for cardiovascular death,and ACEI/ARB was an independent protective factor (P＜0.05).Conclusion T2DM could increase the risk for cerebral infarction and cardiovascular death in patients with NVAF.

The relationship between vascular lesion and serological changes in patients with coronary heart disease and obstructive sleep apnea hypopnea syndrome / 天津医药

Objective To investigate the relationship between vascular lesion and serological changes in patients with coronary heart disease (CHD) complicated with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods According to the standard, a total of 168 patients of OSAHS complicated with CHD were selected in this study. Those patients were divided into 3 groups according to the apnea hypopnea index (AHI) level:light group (AHI, 5-14/h), moderate group (AHI, 15-30/h) and severe group (AHI,>30/h). Syntax scores were performed on three groups according to coronary angiography results. The data of hemoglobin (Hb), platelet count (PLT), fibrinogen (FIB), D-Dimer (DD), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triacylglycerol (TG), alanine aminotransferase (ALT), aspartate transaminase (AST), uric acid (UA), creatinine (Cr) and echocardiographic examination index were collected and analyzed in three groups. Results The Syntax score was significantly higher in severe group than that in mild and moderate groups (P 0.05). Conclusion The serology and cardiac structure can change gradually in severe OSAHS patients, and the coronary artery lesion will be more complex. Therefore, the clinical treatment should pay attention to screening for OSAHS in patients with coronary heart disease.

Clinical application evaluation of thrombus aspiration on emergency percutaneous coronary intervention of patients with ST-segment elevation type of myocardial infarction / 中国综合临床

Objective To investigate the influence of thrombus aspiration on ventricular remodeling of patients with ST?segment elevation type of myocardial infarction ( STEMI ) who underwent emergency percutaneous coronary intervention ( PCI) and its predicative value for patients′ prognosis. Methods Three hundred and eight patients who were diagnosed with STEMI line emergency PCI and hospitalized in the Cardiology Department of Jinghai Clinical College of Medical University of Tianjin from March 2011 to March 2014 were retrospective analyzed, including 152 patients received thrombus aspiration during primary PCI as thrombus aspiration group,and the remaining 156 patients without thrombus aspiration as control group. Indexes of myocardial perfusion levels such as ST?segment resolution 2 hours after PCI and TIMI myocardial perfusion grade were measured in all patients. All patients accepted echocardiography examinations to detect left ventricular end diastolic diameter(LVED) and left ventricular ejection fraction(LVEF) 10 days after PCI. The indexes differences of the two groups,secondary end points major cardiac adverse events(MACE) at 6 months were compared. Results There was no statistical difference between the ratio of two groups for ST segment fell more than 50%( 78. 9%( 120/152) vs. 71. 2%( 111/156) ,χ2=0. 428,P=0. 669) . But for ST segment fell more than 70%,the ratio of the thrombus aspiration group was significantly higher than that in the control group ( 73. 7%( 112/152 ) vs. 47. 4% ( 74/156 ) , χ2 = 4. 701, P = 0. 001 ) . Two groups of patients were treated by echocardiography 10 days after PCI,showed the LVED in the thrombus aspiration group was lower than that in the control group((50. 2±4. 7) mm vs. (51. 6±4. 6) mm,t=2. 642,P=0. 008),while the LVEF value was higher than that in the control group((56. 9±4. 9)% vs. (49. 4±4. 2)%,t=14. 434,P=0. 001). Recurrent angina pectoris decreased significantly in the thrombus aspiration group at 6 months ( 4. 61% ( 7/152 ) vs. 10. 90%(17/156),χ2=2. 056,P=0. 040). Conclusion STEMI patients adopt thrombus aspiration that undergoing emergency PCI,not only can improve myocardial reperfusion,especially microcirculation reperfusion, but also can improve the left ventricular systolic function and the prognosis of patients.

Mechanisms of ERK1/2 signaling pathway participate in inflammatory reaction caused by coronary heart disease / 天津医药

Objective To investigate the effects of ERK1/2 signaling pathway on coronary atherosclerosis-associated inflammatory reaction in autopsy cases. Methods Forty-five autopsy cases were divided into three groups:coronary arterydisease (CHD)-associated death group, CHD group and control group (n=15 for each group). The inflammatory cell infiltration in myocardial tissues was observed through staining leucocyte common antigen (CD45) by HE and immunohistochemistry method. The protein expression level and distribution in extracellular signal-regulated kinase 1/2 (t-ERK1/2) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) of myocardial tissues were detected by immunohistochemistry and Western-blot assay. The expression level of tumor necrosis factor α (TNF-α) was determined using semiquantitative RT-PCR analysis. The activity of nuclear factor (NF)-κB was assessed using electrophoretic mobility shift assay (EMSA). Results Compared with CHD and control groups, myocardial inflammatory cell counts, phosphorylation of ERK1/2, TNF-α mRNA expression and NF-κB activation were significantly increased in CHD-associated death group (P < 0.05). Western blot analysis showed that the phosphorylation of ERK1/2 was positively correlated with expression of TNF-αmRNA and the number of inflammatory cells in CHD-associated death group (r=0.675, P<0.01;r=0.893, P<0.01). Conclusion Results reveal that the activation of ERK1/2 signaling pathway is considered as an important mechanism for coronary atherosclerosis caused myocardial inflammatory reaction, which indicates that the inhibition of ERK1/2 signal transduction pathway may become a potential new target for prevention and treatment of atherosclerotic coronary infarction.