Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Endothelium-specific endothelin-1 expression promotes pro-inflammatory macrophage activation by regulating miR-33/NR4A axis.

The hallmark of atherogenesis is characterized as endothelial dysfunction and subsequent macrophage activation. Although our previous study has demonstrated that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying mechanism remains deeply investigation. Enhanced atherosclerotic plaques were observed in endothelium-specific ET-1 overexpression ApoE-/- mice (eET-1/ApoE-/-) concomitant with increased secretion of pro-inflammatory adhesion molecules and cytokines. The conditional media used for culturing human umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to OX-LDL stimulation, was collected and utilized for bone marrow-derived macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression related to classical M1 macrophages but decreased alternative activated M2 macrophages genes expression in macrophage culturing with the conditional media. Furthermore, consistent regulations of macrophage polarization were observed using isolated exosomes from the conditional media. More importantly, we noticed that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, while bioinformatics analysis further indicated that miR-33 directly targeted NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such effects could be reversed by ET-1 knockdown. Taken together, our study indicated that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to macrophages and subsequently promote pro-inflammatory macrophage activation by directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A axis was the important mechanism underlying the effect of ET-1 on macrophage activation and indicated that ET-1 may act as a promising target for atherosclerosis management.

Holistic review and meta-analysis of independent impact of the residual SYNTAX score on prognosis in patients with acute coronary syndrome.

Objectives. The appropriate extent of revascularization following primary intervention is unknown. We conducted a systematic review and meta-analysis of residual Syntax score (rSS) to predict the outcomes and provide guide to optimal management of revascularization following primary intervention. Designs. Previously published studies from 2007 to 2020 assessing the prognostic impact of rSS after ACS were included for this meta-analysis. The primary endpoint was defined as the major adverse clinical events (MACE) in multivariable analysis. The risk ratios (RRs) with 95% confidence intervals (CI) were calculated using the RevMan 5.4 software. Results. A total of 8,157 participants complicated with ACS from 12 clinical studies were included in this analysis. Based on the wide range of rSS studies available, we classified it into two major groups: rSS < 8 and rSS ≥ 8. In multivariate analysis, the rSS was an independent risk marker for MACE [RR = 1.04 (95%CI; 1.00-1.08)], all-cause mortality [RR = 1.05 (1.03-1.07)] and cardiovascular death [RR = 1.05 (1.03-1.07)]. Patients with incomplete revascularization (ICR) showed higher prevalence of MACE along with all-cause mortality, cardiovascular morality, and recurrent myocardial infarction without significant heterogeneity [RR = 1.60 (1.03-1.07), 2.30 (1.57-3.38), 3.57 (2.09-6.10) and 1.70 (1.38-2.09), respectively]. The patients with rSS ≥ 8 presented higher frequency of all-cause mortality [RR = 2.99 (2.18-4.09)], cardiovascular death [RR = 3.32 (2.22-4.95)], and recurrent myocardial infarction [RR = 1.64 (1.34-2.02)]. Conclusion. The meta-analysis indicated that an rSS value of 8 could be a reasonable cut-off for incomplete revascularization after ACS and is an efficient tool to guide revascularization. In future, detailed research should focus on investigation of the optimal value of the rSS score.

Pulmonary vein isolation guided by moderate ablation index targets combined with strict procedural endpoints for patients with paroxysmal atrial fibrillation.

INTRODUCTION: Ablation index (AI)-guided radiofrequency ablation has been increasingly used for the treatment of drug-resistant paroxysmal atrial fibrillation (AF)，but the optimal AI targets remain to be determined. We aimed to examine the efficacy and safety of catheter ablation guided by moderate AI values but more strict procedural endpoints in patients with paroxysmal AF. METHODS: We conducted a retrospective review of a consecutive series of patients who received their first AI-guided ablation for paroxysmal AF from 2017 to 2018. The standard procedural protocol recommends AI targets as follows: anterior: 400-450; posterior: 280-330; and roof/inferior wall: 380-430. After circumferential pulmonary vein isolation (PVI), we performed bipolar pacing along the ablation line, adenosine triphosphate (ATP)-provocation, and waited for 30 min to verify PVI. The primary clinical outcome was the rate of freedom from AF recurrence at 12 months. RESULTS: A total of 140 consecutive patients were included. The mean procedure and ablation times were 132.2 ± 30.2 min and 24.2 ± 7.9 min, respectively. The first-pass isolation and final isolation rates were documented in 49.3% and in 100% of the patients, respectively. At 12 months, single-procedure freedom from atrial tachyarrhythmias was observed in 92.1% of patients. No major procedure-related complications were encountered. CONCLUSIONS: Moderate AI-guided catheter ablation is highly effective for the treatment of drug-refractory paroxysmal AF in real-world settings. Over 90% of patients achieved single-procedure arrhythmia-free survival at 1 year. The outcome was obtained without major complications and the procedure involved relatively short procedure and ablation times.

The Elabela-APJ axis: a promising therapeutic target for heart failure.

Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin-APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA-APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA-APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA-APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA-apelin-APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.

Cardiovascular complications of SARS-CoV-2 infection (COVID-19): a systematic review and meta-analysis.

Coronavirus Disease 2019 (COVID-19) originated in Wuhan, China in December 2019 and rapidly spread worldwide. Herein, we conducted a systematic review and meta-analysis to find the association between COVID-19 and cardiovascular complications. We conducted a systematic literature search of the PubMed and Embase databases from 01 December 2019 to 30 November 2020. We then statistically analyzed the incidence of cardiovascular complications in COVID-19 patients. We included 3044 confirmed COVID-19 cases from 12 studies. The most common cardiovascular complications in COVID-19 patients were myocardial injury (21.2%, 95% CI 12.3-30.0%) and arrhythmia (15.3%, 95% CI 8.4-22.3%), followed by heart failure (14.4%, 95% CI 5.7-23.1%) and acute coronary syndrome (1.0%, 95% CI 0.5-1.5%). The pooled incidence of heart failure, arrhythmia and myocardial injury in non-survivors were 47.8% (95% CI 41.4-54.2%), 40.3% (95% CI 1.6-78.9%) and 61.7% (95% CI 46.8-76.6%), respectively. Also, the data separately showed significantly higher incidence of heart failure and cardiac injury in non-survivors (relative risks = 5.13, 95% CI 2.46-10.7, Z = 4.36, P = 0.017) and (relative risks = 6.91, 95% CI 3.19-14.95, Z = 4.91, P = 0.009). Myocardial injury and arrhythmia were the most common complications in COVID-19 patients. Myocardial injury and heart failure were more common in patients who died, regardless of a history of cardiovascular disease. The incidence of heart failure and myocardial injury were higher in non-survivors compared to the survivors. Accordingly, in addition to basic support, cardiac reactions of patients with confirmed COVID-19 with or without underlying cardiovascular diseases should be closely monitored.

Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors. METHODS: A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension. RESULTS: Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels. CONCLUSIONS: ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

The long-term impact of a chronic total occlusion in a non-infarct-related artery on acute ST-segment elevation myocardial infarction after primary coronary intervention.

OBJECTIVES: To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. METHODS: The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. RESULTS: The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47-10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P < 0.01), an in-hospital Killip class ≥ 3 (OR = 4.32, 95% CI: 1.71 ~ 10.95, P < 0.01), and the presence of renal insufficiency (OR = 5.32, 95% CI: 1.49 ~ 19.01, P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P < 0.01) and the presence of renal insufficiency (OR = 5.61, 95% CI: 1.19 ~ 26.39, P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO. CONCLUSIONS: The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

Circulating exosomal long non-coding RNAs in patients with acute myocardial infarction.

Exosomes are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized in acute myocardial infarction (AMI). However, the regulatory role of exosomal long non-coding RNAs (lncRNAs) in AMI remains largely unclear. Exosomes were isolated from the plasma of AMI patients and controls, and the sequencing profiles and twice qRT-PCR validations of exosomal lncRNAs were performed. A total of 518 differentially expressed lncRNAs were detected over two-fold change, and 6 kinds of lncRNAs were strikingly elevated in AMI patients with top fold change and were selected to perform subsequent validation. In the two validations, lncRNAs ENST00000556899.1 and ENST00000575985.1 were significantly up-regulated in AMI patients compared with controls. ROC curve analysis revealed that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 yielded the area under the curve values of 0.661 and 0.751 for AMI, respectively. Moreover, ENST00000575985.1 showed more significant relationship with clinical parameters, including inflammatory biomarkers, prognostic indicators and myocardial damage markers. Multivariate logistic model exhibited positive association of ENST00000575985.1 with the risk of heart failure in AMI patients. In summary, our data demonstrated that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 are elevated in patients with AMI, functioning as potential biomarkers for predicting the prognosis of pateints with AMI.

Identification of circumferential pulmonary vein isolation responders among patients with persistent atrial fibrillation: clinical value of the sequential low-dose ibutilide test.

AIMS: Circumferential pulmonary vein isolation can be effective as sole treatment for persistent atrial fibrillation. However, identifying those patients who will respond to this therapy remains a challenge. We investigated the clinical value of the sequential low-dose ibutilide test for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation is effective as sole therapy. METHODS AND RESULTS: In a prospective cohort of 180 consecutive patients with persistent atrial fibrillation, intravenous low-dose (0.004 mg/kg) ibutilide was administered 3 days before ablation and after the completion of circumferential pulmonary vein isolation. In patients in whom ibutilide did not terminate atrial fibrillation pre-procedurally, but successfully terminated it intraprocedurally, no further atrial substrate modification was performed. Pre-procedural low-dose ibutilide failed to terminate the arrhythmia in all patients with persistent atrial fibrillation, while pulmonary vein isolation ± low-dose ibutilide terminated persistent atrial fibrillation in 55 (30.6%) of them (PsAF group 1). The remaining 125 (69.4%) patients underwent electrogram-based ablation (PsAF Group 2). The control group comprised 379 consecutive patients with paroxysmal atrial fibrillation who underwent pulmonary vein isolation over the same period. At 24 months follow-up, 39 (70.9%) patients in PsAF Group 1 and 276 (72.8%) patients in the control group were free from atrial tachyarrhythmias (P = NS); the arrhythmia-free rates in both groups were higher than that in PsAF group 2 (58.4%, P = 0.005). CONCLUSION: The sequential low-dose ibutilide test is a simple method for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation alone is an appropriate treatment strategy.

Electrocardiographic morphology during left bundle branch area pacing: Characteristics, underlying mechanisms, and clinical implications.

AIMS: In this study, we investigated the characteristics and underlying mechanisms of the electrocardiographic (ECG) morphology during left bundle branch area pacing (LBBAP), which have not been systematically described. METHODS: Patients with indications for permanent cardiac pacing underwent LBBAP attempts. The ECGs of patients with confirmed left bundle branch (LBB) capture were compared with those of individuals with right bundle branch block (RBBB) on 12-lead ECG. Intracardiac electrograms recorded during implantation were analyzed in all patients who underwent pacing. RESULTS: LBBAP was successfully achieved in 87.5% (56/64) of patients. The QRS morphologies in lead V1 during LBBAP, which typically demonstrated Qr (60.7%), qR (19.6%), rSR' (7.1%), or QS (12.5%) patterns, differed from those of native RBBB, which featured rsR' (57.5%), M shape (23.7%), or monophasic R patterns (18.7%). The terminal R' wave duration in lead V1 was significantly shorter during LBBAP than during native RBBB (51 ± 12 ms vs 85 ± 19 ms, p < 0.001). LBB potentials were recorded in 66.1% (37/56) of the LBBAP patients. No significant differences in ECG characteristics were found between LBBAP with and without recorded LBB potentials. The presence of bundle branch block during LBBAP significantly prolonged QRS duration, R wave peak time, and terminal R' wave duration in lead V1 . CONCLUSION: LBBAP-ECG patterns are characterized by a shorter terminal R' wave duration in lead V1 compared with that of native RBBB configurations. Bundle branch conduction integrity has an impact on ECG characteristics during LBBAP.

Pace capture and adenosine triphosphate provocation are complementary rather than mutually exclusive methods to ensure durable pulmonary vein isolation.

INTRODUCTION: Adenosine triphosphate (ATP)-provoked dormant conduction (DC) and pacing for unexcitability are used to identify conduction gaps along the ablation lines after circumferential pulmonary vein isolation (CPVI). We aim to determine whether ATP provocation and pacing are interchangeable as endpoints for ablation of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: A total of 107 patients with PAF were randomly divided into two groups after completion of CPVI. In group I (A-P group, n = 53), ATP was administered first. If DC was uncovered, additional ablation was performed until ATP tests were negative. Bipolar pacing along the ablation line was performed subsequently. In group II (P-A group, n = 54), the same protocol was used, but the pacing and the ATP tests were performed in the opposite sequence. The 12-month ablation outcomes of all patients were compared with those of a historical control group of 107 patients with PAF in whom only ATP test was performed. Regardless of which test was performed first, the other modality still identified conduction gaps. In group I, pacing maneuvers identified gaps in 49% (n = 26) of patients who had negative ATP tests. In group II, ATP tests uncovered DC in 18.5% (n = 10) of patients in whom pacing identified no gaps. After 12 months, a higher proportion of patients (91.6%) were free from atrial tachyarrhythmias compared with the historical control group (81.3%; P = 0.031). CONCLUSION: Pacing along the ablation lines and ATP provocation are complementary tests for evaluating the durability of CPVI and can lead to better long-term outcomes when used in combination.

Palmitic Acid Increases Endothelin-1 Expression in Vascular Endothelial Cells through the Induction of Endoplasmic Reticulum Stress and Protein Kinase C Signaling.

OBJECTIVE: We investigated the regulation of endothelin-1 (ET-1) expression in in vivo high-fat diet (HFD)-fed mice and in vitro cultured human aortic endothelial cells (HAECs). METHODS: Male C57BL/6 mice were fed on standard chow, serum was prepared, and ET-1 levels were analyzed using an ELISA kit. Quantitative PCR was performed using iQ SYBR Green Supermix. Statistical significance was assessed using SPSS, with p < 0.05 considered significant. RESULTS: The serum ET-1 content and endothelial expression of ET-1 mRNA were increased in the HFD-fed mice compared to the chow-fed control mice. Moreover, the mRNA expression of ET-1 was significantly increased in cultured HAECs in response to acute (< 24 h) and chronic (12-16 days) treatments with palmitic acid (PA), one of the most abundant saturated fatty acids in obesity. We found that the induction of ET-1 expression by PA was abolished by pretreating the cells with the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid or the protein kinase C (PKC) inhibitor Gö 6850. CONCLUSION: Our findings demonstrate for the first time that PA increases ET-1 expression in endothelial cells through the induction of ER stress and the activation of PKC, providing novel mechanistic insights into the pathogenesis of obesity-associated hypertension and cardiovascular diseases.

Circulating Long Noncoding RNA LIPCAR Acts as a Novel Biomarker in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND Long noncoding RNAs (lncRNAs) recently have been implicated in the pathological processes of cardiovascular diseases. In this study, LncRNADisease database and PubMed database were used to screen myocardial infraction (MI)-related lncRNAs and to investigate the diagnostic role of lncRNAs in ST-segment elevation myocardial infraction (STEMI). MATERIAL AND METHODS Forty-six patients with STEMI and 40 healthy controls were included in the study. Venous blood samples acquired at different time points and the expression levels of lncRNAs in plasma were measured by qRT-PCR. In addition, other blood samples were collected before and after percutaneous coronary intervention (PCI). Correlation analysis and receiver operating characteristic (ROC) curve were used to assess the diagnosis value of the markers. All included patients were followed up for 12±1 months. RESULTS Nine MI-related lncRNAs were selected from the database. The qRT-PCR results showed that the expression of hypoxia inducible factor 1A antisense RNA 2 (aHIF), member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), and mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) were significantly increased in patients with STEMI compared to the control patients. The ROC curve showed that LIPCAR (AUC=0.782, 95% CI: 0.707-0.0.894) had better diagnostic accuracy. Moreover, correlation analysis indicated that LIPCAR were positively correlated with myocardial enzymes and negatively correlated with left ventricular ejection fraction. The level of LIPCAR in STEMI patients after PCI was lower (P<0.05). Multivariate regression analysis indicated that higher levels of LIPCAR were independent predictors of major adverse cardiovascular events in patients with STEMI (HR=5.93; 95% CI, 1.46-9.77; P=0.001). CONCLUSIONS Highly expressed LIPCAR in plasma may serve as a warning sign for the diagnosis of STEMI.

[Adjusting Platelet Counts for Platelet Aggregation Tests].

OBJECTIVE: To explore a better method to adjust platelet counts for light transmission aggregometry (LTA). METHODS: Blood samples from 36 healthy participants aged from 18 to 50 yr. were collected.Platelet-rich plasma (PRP) was diluted using platelet-poor plasma (PPP) and physiological saline (PS),respectively,in a ratio of 1.5,2,2.5 and 3 times. Platelet aggregation was induced by adenosine diphosphate (ADP),arachidonic acid (ARA),collagen (COL), epinephrine (EPI),or ristocetin (RIS). The maximal aggregation rates (MAs) of different approaches were compared. We also compared the MAs induced by RIS between PRP-obtained-PPP and whole blood-obtained-PPP (2 100×g, 5 min). RESULTS: Compared with the original PRP,the MAs induced by ADP,ARA,and EPI decreased in PPP-adjusted PRP (significant at 2-3 times dilution ratio,P<0.05),but not in PS-adjusted PRP (P>0.05). The MA induced by RIS decreased in PS-adjusted PRP (significant at all dilution ratios,P<0.05),but not in PPP-adjusted PRP (P>0.05). No changes in the MA induced by COL were found in PS-adjusted PRP and PPP-adjusted PRP (P>0.05). Whole blood-obtained-PPP (2 100×g, 5 min) had the same MA induced by ristocetin compared with PRP-obtained-PPP (P>0.05). CONCLUSION: PS is recommended for adjusting platelets counts for platelet aggregation induced by ADP,ARA,COL and EPI. Whole blood-obtained-PPP (2 100 ×g, 5 min) is recommended for RIS-induced aggregation as a matter of convenience.

A novel block at chromosome 12q24.1 is associated with coronary artery disease in Han Chinese populations.

OBJECTIVE: The aim of this study was to refine the chromosomal region 12q24.1 associated with coronary artery disease in Han Chinese populations. METHODS AND RESULTS: Twenty tagging single nucleotide polymorphisms covering 1.2 Mb of chromosomal 12q24.1 were selected and genotyped in three geographically isolated case-control populations consisting of 7076 coronary artery disease (CAD) patients and non-CAD participants. In addition to replication of the previous block (block 1), we identified a novel block (block 2) associated with CAD. In a combined analysis, the odds ratio (95% confidence interval, permuted P value) were 0.79 (0.72-0.86, 8.358×10) and 1.24 (1.13-1.36, 2.576×10) for haplotypes ATGGG and GCACA in block 1 and 1.22 (1.14-1.30, 6.484×10) and 0.82 (0.77-0.88, 6.484×10) for haplotypes GA and AG in block 2, respectively. Protective alleles of two index single nucleotide polymorphisms decreased the expression of NAA25 (P=0.034), but did not alter the expression of other genes within block 2. CONCLUSION: We identified a novel block associated with CAD at chromosomal 12q24.

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine.

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

Associations between plasma total homocysteine, blood pressure stages and pulse wave velocity in Chinese rural community population.

The aim of the study was to examine the associations among plasma total homocysteine (tHcy) and blood pressure (BP) stages and brachial-ankle pulse wave velocity (ba-PWV) in a Chinese rural community population. In this cross-sectional study, 2148 rural community subjects with normotension and mild hypertension (HTN) were classified into four groups according to ba-PWV level. Multivariate regression showed that ba-PWV was significantly and independently correlated with tHcy (ß = 5.32, p < 0.001) in the entire study population. Moreover, ba-PWV showed a significant increase with increasing plasma tHcy level in subjects with both high normal BP and grade 1 HTN (p < 0.05). Compared with optimal BP stage, ba-PWV was significantly associated with high normal BP stage (ß = 193, p < 0.001) and grade 1 HTN (ß = 413, p < 0.001).There was a statistical interaction effect between high normal BP stage and optimal BP stage (p = 0.045). The similar result was found between subjects with optimal BP and those with grade 1 HTN (p = 0.037). In conclusion, tHcy was independently correlated with ba-PWV in subjects with high normal BP and grade 1 HTN. High normal BP and grade 1 HTN may worsen the impact of tHcy on arterial stiffness in a Chinese rural community population.

Downregulation of microRNA-19b contributes to angiotensin II-induced overexpression of connective tissue growth factor in cardiomyocytes.

OBJECTIVES: The present study was designed to decipher the molecular mechanisms underlying angiotensin (Ang) II-induced overexpression of connective tissue growth factor (CTGF) in cultured cardiomyocytes. METHODS: Cardiomyocytes isolated from 1- to 3-day-old neonatal rats were cultured and treated with 100 nM Ang II with or without pretreatment with 10 nM telmisartan, an Ang II type 1 receptor antagonist. The role of microRNA (miR)-19b in the regulation of Ang II-induced CTGF expression was evaluated in cultured cardiomyocytes with quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. RESULTS: We provide several lines of evidence to show that miR-19b contributes to the Ang II-induced overexpression of CTGF in cultured cardiomyocytes. Firstly, administration of Ang II decreased the level of miR-19b dramatically (p < 0.05 vs. control), which was abolished by telmisartan. Secondly, Ang II increased the level of CTGF significantly (p < 0.05 vs. control), which was also prevented by pretreatment with telmisartan. Thirdly, overexpression of miR-19b decreased CTGF levels (p < 0.05 vs. control). Finally, transfection of miR-19b into cardiomyocytes prevented the upregulation of CTGF induced by Ang II. CONCLUSION: Downregulation of miR-19b contributes to Ang II-induced overexpression of CTGF in cultured cardiomyocytes.

High blood pressure is associated with increased risk of future fracture, but not vice versa.

The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997-2015 (N = 10,227), 2000-2015 (N = 10,547), 2004-2015 (N = 10,909), and 2006-2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95-1.90) in 1997-2015, 1.40 (1.04-1.88) in 2000-2015, 1.32 (0.98-1.78) in 2004-2015, and 1.38 (1.01-1.88) in 2006-2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96-1.72) in 1997-2015, 1.18 (0.94-1.49) in 2000-2015, 1.12 (0.89-1.40) in 2004-2015, and 1.09 (0.85-1.38) in 2006-2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.