Oral anticoagulant prescribing in elderly patients above and below age 80 with atrial fibrillation
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BACKGROUND: Oral anticoagulation is efficient to prevent ischemic stroke in atrial fibrillation (AF), but in very old patients, physicians always remain cautious to use anticoagulants concerning the bleeding risk. This research aims to investigate the current situation of oral anticoagulation therapy in very old (≥ 80 years) AF patients. MATERIALS AND METHODS: We carried out a cross-sectional study in an urban area in China from 2014 to 2016. Characteristics of the very old patients (age ≥ 80 years) and the younger patients (age < 80 years) were compared. Logistic analysis was used to estimate the association between oral anticoagulation therapy and CHA2DS2-VASc score. RESULTS: A total of 1,000 AF patients were enrolled; 306 were very old patients, and 694 were younger patients. In the very old group, 48.0% were women, and the average age was 84.12 ± 3.62 years. In the younger group, 35.3% were women, and the average age was 66.92 ± 9.02 years. CHA2DS2-VASc score was 2.8 ± 1.7 in the younger group and 4.5 ± 1.5 in the very old group (p < 0.001). The proportion of oral anticoagulation was low in patients with AF (31.8%) and even lower in very old patients compared to younger patients (24.5 vs. 35.0%, p = 0.004). Moreover, oral anticoagulation therapy was strongly associated with CHA2DS2-VASc scores only in the younger group, but not in the very old group, which means the very old patients were not treated with oral anticoagulation according to their elevated CHA2DS2-VASc scores. CONCLUSION: Anticoagulants were underused in AF patients, particularly in very old patients. Evidence is accumulating that the very old patients could still benefit from anticoagulants so that physicians should not exclude such patients from anticoagulation only because of their older age.

The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis.

BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. METHODS: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells. RESULTS: LPS stimulation significantly aggravated cardiac inflammation and tissue injury in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater elevation, which may be related to Reactive oxygen species (ROS) stress involved mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 treatment significantly ameliorated cardiac inflammation and tissue injury compared with untreated group. CONCLUSION: Increased circulating mtDNA combined with upregulated TLR9 expression may corporately play a role in EAM as well as TLR4 activation mediated cardiac inflammation and injury.

A meta-analysis of ß1-adrenergic receptor gene polymorphisms in idiopathic dilated cardiomyopathy.

Published data on the association between ß1-adrenergic receptor gene polymorphisms and idiopathic dilated cardiomyopathy (IDCM) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 12 case-control studies including 2642 cases and 3136 controls provided data on the association between ß1-adrenergic receptor gene polymorphisms and susceptibility to IDCM. Overall, no significantly elevated risk was associated with Arg389Gly polymorphisms for all genetic models. In the subgroup analysis by ethnicity, no statistically increased risk was found for Gly389Gly versus Arg389Arg (OR 0.73; 95% CI 0.54-0.99; Ph=0.35) and Gly389Gly versus Arg389Arg+Arg389Gly (OR 0.75; 95% CI 0.55-1.01; Ph=0.52) among Europeans. Meanwhile, significantly increased risk was found among Asians based on the relatively small sample size. Further, significantly elevated IDCM risk was associated with Ser49Gly polymorphisms for all genetic models. When stratified by ethnicity, statistical association was found among Asians for Gly49Gly versus Ser49Ser (OR 4.56; 95% CI 1.36-15.23; Ph=0.10) and Gly49Gly versus Ser49Ser+Ser49Gly (OR 4.49; 95% CI 1.33-15.15; Ph=0.12), but not among Europeans. In summary, this meta-analysis suggests that no statistically increased risk was found between ß1-adrenergic receptor gene polymorphisms and susceptibility to IDCM among Europeans.

A meta-analysis of HLA-DR polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR polymorphism and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 19 case-control studies including 1,378 cases and 10,383 controls provided data on the association between HLA-DR polymorphism and genetic susceptibility to IDC. Overall, statistically elevated frequencies of HLA-DR4 (OR 1.58; 95% CI 1.21-2.07; P=0.0009) and HLA-DR5 (OR 1.35; 95% CI 1.05-1.73; P=0.02) alleles were found in patients with IDC compared with controls. Individuals with HLA-DR3 antigen have a protective effect against IDC (OR 0.72; 95% CI 0.58-0.90; P=0.004). In summary, this meta-analysis indicated that certain HLA-DR alleles may be genetic markers for susceptibility and resistance to IDC.

Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel.

Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk for recurrent ischemic events. Cytochrome P450 (CYP) polymorphisms have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Published data on the association between CYP2C19*2 polymorphism and atherothrombotic events are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight prospective cohort studies including 2,345 patients carrying CYP2C19*2 variant allele and 5,935 cases with the wild-type genotype were included in this meta-analysis. Overall, borderline statistically significantly elevated risk of adverse clinical events was associated with genotyping 681G>A polymorphism (for AA + GA vs. GG: OR, 1.46; 95% CI, 1.01 to 2.13; P = 0.05). The summary odds ratio showed a significant association between the CYP2C19*2 polymorphism and an increased risk of cardiac mortality in the follow-up period (OR, 2.07; 95% CI, 1.22 to 3.52; P = 0.007). When studies evaluating myocardial infarction, stent thrombosis, and ischemic stroke, the presence of the variant allele was associated with significantly increased risks of recurrent atherothrombotic events. In summary, this meta-analysis indicated that CYP2C19*2 carrier status is significantly associated with an increased risk of adverse cardiovascular events.

Varied association of prothrombin G20210A polymorphism with coronary artery disease susceptibility in different ethnic groups: evidence from 15,041 cases and 21,507 controls.

Published data on the association between prothrombin G20210A polymorphism and coronary artery disease (CAD) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 42 case-control studies including 15,041 cases and 21,507 controls were included in this meta-analysis. Overall, significantly elevated CAD risk was associated with prothrombin G20210A polymorphism (OR, 1.22; 95% CI 1.07-1.40; P=0.003) when 39 eligible studies were pooled into the meta-analysis. In the subgroup analysis, borderline statistically increased risk was found for myocardial infarction in 22 case-control studies (OR, 1.27; 95% CI 1.00-1.61; P=0.05). When stratified by ethnicity, significantly elevated risk was found in Europeans (OR, 1.19; 95% CI, 1.02-1.38; P=0.02). However, no statistical differences were found among Americans and Asians. In summary, this meta-analysis indicated that prothrombin G20210A allele is a low-penetrant risk factor for developing CAD in Europeans.

[Relationship between post-stenting coronary thrombolysis in myocardial infarction flow and plasma von Willebrand factor and ADAMTS-13 levels in patients with ST segment elevation myocardial infarction].

OBJECTIVE: To investigate the relationship between post-stenting coronary thrombolysis in myocardial infarction (TIMI) flow and plasma von Willebrand factor (vWF) and its cleaving protease (ADAMTS-13) levels in patients with ST segment elevation myocardial infarction (STEMI). METHODS: STEMI patients who underwent primary percutaneous coronary intervention (PCI) and stenting between September, 2007 and December, 2009 were enrolled. According to the post-stenting TIMI flow, patients were divided to TIMI ≤ 2 group (n = 43) and TIMI 3 group (n = 43). Patients with chest pain or dyspnea and normal coronary angiographic results served as control group (n = 43). The levels of vWF and ADAMTS-13 were measured by ELISA at three time points: immediately after admission, beginning of PCI and 1 week after PCI. RESULTS: Levels of vWF in STEMI patients at all 3 time points were significantly higher than in control patients, and the level of vWF was significantly higher in TIMI ≤ 2 group than in TIMI 3 group [at admission: (6721.83 ± 1380.58) U/L vs. (4786.12 ± 2362.01) U/L, P < 0.05; at the beginning of PCI: (5744.65 ± 1240.71) U/L vs. (3011.33 ± 2270.40) U/L, P < 0.05 and at 1 week after PCI: (2001.48 ± 931.70) U/L vs. (1365.17 ± 724.12) U/L, P < 0.05]. ADAMTS-13 levels were similar among groups at admission and at beginning of PCI, however, the level of ADAMTS-13 at 1 week after PCI was significantly higher in TIMI ≤ 2 group than that in TIMI 3 group [(406.93 ± 101.44) mg/L vs. (270.34 ± 115.12) mg/L, P < 0.001]. Logistic regression analysis showed that both vWF at admission (OR = 1.917, P < 0.01) and vWF at the beginning of PCI (OR = 2.016, P < 0.01) were risk factors of TIMI ≤ 2. CONCLUSION: Increased vWF during peri-PCI periods was associated with post-stenting coronary TIMI ≤ 2 after primary PCI in STEMI patients, and the imbalance between vWF and ADAMTS-13 may thus play an important role in the development of slow flow post PCI.

Cardiac matrix remodeling following intracoronary cell transplantation in dilated cardiomyopathic rabbits.

Cellular cardiomyoplasty has been proposed as a promising therapeutic strategy for chronic heart failure. Previous studies focused on structural changes in cardiomyocytes to explain the potential benefits for contractile function. However, limited information is available about the cardiac matrix remodeling following cell transplantation in dilated cardiomyopathy (DCM). Here, we established a new animal model of intracoronary bone marrow mononuclear cells (BMMNCs) transplantation to explore extracellular matrix remodeling in adriamycin-induced cardiomyopathic rabbits. In vivo studies demonstrated that BMMNCs transplantation can dramatically delay the progress of collagen metabolism and decrease myocardial collagen volume fraction. The beneficial effects were mediated by attenuating stress-generated over-expression of matrix metalloproteinases (MMPs) in ventricular remodeling. Improved cardiac function may be contributed in part by stem-associated inhibition of extracellular matrix remodeling.

Phosphodiesterase type 5 inhibitors for high-altitude pulmonary hypertension: a meta-analysis.

BACKGROUND: High-altitude pulmonary hypertension (HAPH) is a public health problem in mountainous areas of the world. Treatment options for this condition are unsatisfactory. Recent interest in use of selective phosphodiesterase type 5 (PDE5) inhibitors for pulmonary hypertension has suggested a possible role for these agents in the treatment of HAPH. Preliminary data from several small studies have shown beneficial haemodynamic effects of empirical PDE5 treatment of HAPH but the results of these studies have been challenged. OBJECTIVE: We performed a meta-analysis to explore the potential therapeutic effects of PDE5 inhibitors for HAPH. METHODS: Randomized controlled trials were identified to test the effects of PDE5 inhibitors in HAPH by searching PubMed (inception to June 2009). A standardized protocol with predefined criteria was used to extract details on study design, Jadad score, demographic data, interventions and outcomes. The main outcomes assessed were cardiopulmonary parameters. Treatment effects for continuous variables were presented as weighted mean differences with 95% confidence intervals. RESULTS: Ten clinical trials were identified and included for the meta-analysis. The weighted mean difference in systolic pulmonary artery pressure post-treatment at rest in PDE5 inhibitor-treated subjects was -7.51 mmHg (95% CI -10.87, -4.16; p < 0.0001) compared with controls, whereas the analysis of systolic blood pressure and heart rate demonstrated that no significant effects were observed in the active treatment group at rest and during exercise. CONCLUSIONS: The available evidence suggests PDE5 inhibitors can attenuate altitude-induced pulmonary hypertension without significantly affecting systemic blood pressure or heart rate.

Tenascin C: A Potential Biomarker for Predicting the Severity of Coronary Atherosclerosis.

AIMS: Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide and one of the greatest threats to public health. Tenascin C (TNC) is an extracellular matrix glycoprotein that is found in low concentrations in normal tissues and is enhanced by a range of cardiovascular pathologies. This study aimed to evaluate the value of TNC in assessing the severity of atherosclerosis measured by the Gensini score. METHODS: A total of 157 patients with chest pains who underwent selective coronary angiography for suspected coronary atherosclerosis were enrolled. The patients were divided into the CAD group and non-CAD group according to symptoms and angiography. Demographic data and laboratory analyses were collected. RESULTS: The mean TNC level was significantly higher in the CAD group than in the non-CAD group (p＜0.001). A significant positive correlation between TNC levels and Gensini score (p＜0.01, r=0.672) was found. ROC curve analysis demonstrated that the cutoff value for TNC at 89.48 ng/mL was well differentiated in the CAD and non-CAD groups. Furthermore, TNC was also a good predictor for a higher Gensini score (the third tertile) in the ROC curve analysis. When the cutoff was accepted as 100.91 ng/mL, the sensitivity and specificity were 82.7% and 79%, respectively. CONCLUSION: A significant relationship was found between the Gensini score and serum TNC level. TNC levels can be considered in risk assessments for CAD before angiography.

TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance.

Mitochondrial dynamic imbalance associates with several cardiovascular diseases. However, the role of mitochondrial dynamics in TLR4 activation-mediated dilated cardiomyopathy (DCM) progress remains unknown. A model of experimental autoimmune myocarditis (EAM) was established in BALB/c mice on which TLR4 activation by LPS-EB or TLR4 inhibition by LPS-RS was performed to induce chronic inflammation for 5 weeks. TLR4 activation promoted the transition of EAM to DCM as demonstrated by increased cardiomyocyte apoptosis, myocardial fibrosis, ventricular dilatation, and declined heart function. TLR4 inhibition mitigated the above DCM changes. Transmission electron microscope study showed that mitochondria became fragmented, also with damaged crista in ultrastructure in EAM mice. TLR4 activation aggravated the above mitochondrial aberration, and TLR4 inhibition alleviated it. The mitochondrial dynamic imbalance and damage in DCM development were mainly associated with OPA1 downregulation, which may be caused by elevated TNF-α level and ROS stress after TLR4 activation. Furthermore, OMA1/YME1L abnormal degradation was involved in the OPA1 dysfunction, and intervening OMA1/YME1L in H9C2 significantly alleviated mitochondrial fission, ultrastructure damage, and cell apoptosis induced by TNF-α and ROS. These data indicate that TLR4 activation resulted in OPA1 dysfunction, promoting mitochondrial dynamic imbalance and damage, which may involve in the progress of EAM to DCM.

Relation of Low-Density Lipoprotein Cholesterol to Ischemic Stroke in Patients With Nonvalvular Atrial Fibrillation.

Low-density lipoprotein cholesterol (LDL-C) has been demonstrated as an independent risk factor of ischemic stroke, but the association of LDL-C with ischemic stroke in patients with nonvalvular atrial fibrillation (AF) remains uncertain. Our objective was to explore whether LDL-C could refine stroke stratification in patients with AF. A total of 424 nonvalvular patients with AF with ischemic stroke and 391 ones without ischemic stroke were enrolled. No patient had received antithrombotic therapy. Multivariate logistic regression analysis showed that LDL-C was an independent predictor of ischemic stroke in patients with AF, with the adjusted odds ratio of 2.004 (95% confidence interval 1.624 to 2.473; p <0.001). The receiver operating characteristic analysis revealed that the best cut-off value of LDL-C to predict ischemic stroke in patients with AF was 2.48 mmol/L with 56.3% sensitivity and 66.3% specificity (area under the curve: 0.651, p <0.001). In the subgroup analysis based on different CHA2DS2-VASc scores, the predictive value of LDL-C remained significant in patients with a CHA2DS2-VASc score of ≤5. In conclusion, LDL-C was an independent predictor of ischemic stroke, which could potentially refine stroke stratification in patients with AF. A prospective study with a large number of patients is required to validate the current findings.

Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population.

Tissue factor pathway inhibitor-2 (TFPI-2) may play critical roles in the pathogenesis of atherosclerosis. In this study, we aimed to investigate the association between TFPI-2 gene polymorphisms and coronary atherosclerosis.Four hundred and seven patients with coronary atherosclerosis and 306 individuals with normal coronary artery were enrolled in the present study. Nine single-nucleotide polymorphisms (SNPs) (rs3763473, rs59805398, rs60215632, rs59999573, rs59740167, rs34489123, rs4517, rs4264, and rs4271) were detected with polymerase chain reaction-direct sequencing method. Severity of coronary atherosclerosis was assessed by Gensini score. After the baseline investigation, patients with coronary atherosclerosis were followed up for incidence of cardiovascular events (CVEs).Eight SNPs were in accordance with the Hardy-Weinberg equilibrium, and 8 haplotypes were constructed based on rs59999573, rs59740167, and rs34489123 after linkage disequilibrium and haplotype analysis. Two SNPs (rs59805398 and rs34489123) and 5 haplotypes correlated with coronary atherosclerosis even after adjustment by Gensini score. At follow-up (median 53 months, range 1-60 months), 85 patients experienced CVE. However, there was no strong association between the gene polymorphisms and the occurrence of CVE.Tissue factor pathway inhibitor-2 gene polymorphisms were associated with coronary atherosclerosis in the Chinese population, suggesting that the information about TFPI-2 gene polymorphisms was useful for assessing the risk of developing coronary atherosclerosis, but there was not enough evidence showing it could predict occurrence of CVE.

Cardiac arrhythmias as the initial manifestation of adult primary Sjögren's syndrome: a case report and literature review.

Two middle-aged female patients presenting with heart palpitation and electrocardiogram revealed complex cardiac arrhythmias. A review of systems was positive for dry mouth and transient arthralgia, while laboratory and instrumental tests enabled us to make the diagnosis of primary Sjögren's syndrome (pSS). Cardiac electrophysiology revealed atrioventricular node dysfunction and impaired intraventricular conduction. Prednisone therapy induced a significant improvement in symptoms and electrocardiographic readings. The diagnosis of pSS should be considered in a patient presenting with complex cardiac arrhythmias.

[Effect of Zhenju Jiangya Tablet on the endothelial function of hyperlipidemic rabbits].

OBJECTIVE: To study the effect of Zhenju Jiangya Tablet (ZJ) on the injured endothelial cells and endothelium-dependent relaxation function of hyperlipidemia rabbits. METHODS: Male New Zealand rabbits were randomized into four groups: control group, hyperlipidemia group, ZJ group and sivastatin group. The endothelium-dependent relaxation function was evaluated by APV using intravascular Doppler, and the morphology of endothelial cells was detected by light microscopy and electron microscopy, and nitric oxide synthase was evaluated. RESULTS: ZJ reduced the lesions of hyperlipidemia vessels, and the APV after Ach injection of each group was (1.14+/-0.26), (1.74+/-0.59), (1.22+/-0.37) and (1.17+/-0.41) respectively. The eNOS of each group was (4.21+/-0.37), (1.43+/-0.88), (3.95+/-0.67) and (4.08+/-0.46) nmol x min(-1) x g(-1) respectively. CONCLUSION: ZJ can improve the abnormality of endothelial cells and endothelium-dependent relaxation function of hyperlipidemia.