Objective: To evaluate the association between the tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms and common cardiovascular and cerebrovascular diseases.
Method: A literature-based search was operated through database including PubMed, EMBASE, Cochrane Library, CNKI and WanFang data. Crude odds ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate the strength of the association between TNFSF4 polymorphisms (rs3850641 and rs17568) and the risk of coronary heart disease and stroke.
Results: 11 eligible studies were included in this meta-analysis. It was showed that G allele was not associated with CHD and stroke, compared with A allele (rs3850641: OR 1.02, 95%CI.: 0.89, 1.17; rs17568: OR 1.09, 95%CI.: 0.89, 1.33). Genotypic analysis demonstrated that there was no significantly association between the risk of CHD and stroke and rs3850641 (homozygous comparison (GG vs. AA): OR 1.05, 95%CI.: 0.74, 1.50; heterozygous comparison (GA vs. AA): OR 1.00, 95%CI.: 0.88, 1.13; recessive model (GG vs. GA + AA): OR 1.04, 95%CI.: 0.76, 1.43; dominant model (GG + GA vs. AA): OR 1.01, 95%CI.: 0.88, 1.17). Similarly, no susceptibility between CHD and stroke and rs17568 polymorphism was uncovered (GG vs. AA: OR 1.04, 95%CI.: 0.74, 1.46; GA vs. AA: OR 1.07, 95%CI.: 0.62, 1.83; GG + GA vs. AA: OR 1.13, 95%CI.: 0.82, 1.56; GG vs. GA + AA: OR 1.01, 95%CI.: 0.74-1.39).
Conclusions: The present study demonstrated that there is no significant relationship between TNFSF4 gene polymorphism and cerebrovascular and cardiovascular diseases.

Objective: Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has also been established as an effective cardioprotective agent during ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart.
Methods: A total of 36 rats were equally divided into four groups: control, DOX (30 min, 20 µM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP groups). The isolated hearts were perfused according to the Langendorff method. Cardiac parameters, including left ventricular developed pressure (LVDP), heart rate (HR), coronary flow (CF), and rate pressure product (RPP; LVDP×HR) were measured. Lactate dehydrogenase (LDH) concentration was also assessed.
Results: At the end of the baseline period, the RPP, HR, and CF values were lower in the DOX group than in the control group (p<0.01). Meanwhile, there were no significant differences between the values of cardiac function parameters in the DOX+APAP and control groups. In the reperfusion period, the RPP and CF values were significantly increased in the DOX+APAP group compared with the DOX group (p<0.05). Furthermore, the LDH concentration was decreased in the DOX+APAP group compared with the DOX group.
Conclusion: APAP perfusion protected the hearts against DOX-induced cardiotoxicity in the baseline and ischemia/reperfusion conditions. These findings can be explained by the effect of APAP on antioxidant capacity and mitochondrial permeability transition pores.

Objective: Despite revascularization and optimal medical treatment (OMT), patients with angina often have a reduced quality of life due to inadequate relief from symptoms. Recent studies have shown that the application of shock waves may reduce angina symptoms and improve quality of life, exercise capacity, and myocardial perfusion due to the stimulation of angiogenesis. However, there is limited evidence due to small, single-arm, single-center studies of low to moderate quality. The purpose of this study is to evaluate the impact of cardiac shock wave therapy (CSWT) on exercise tolerance and angina symptoms in patients with coronary artery disease and objective evidence of myocardial ischemia who cannot undergo traditional revascularization and experience angina despite OMT in comparison to sham procedure.
Methods: We designed a randomized, triple-blind, placebo-controlled, multicentre trial (NCT02339454) to assess the efficacy of CSWT in addition to OMT in patients with stable angina and myocardial ischemia documented by exercise treadmill test (ETT). All patients were treated with stable doses of standard medical treatment 4 weeks before screening. An increase in the total exercise duration on ETT by ≥90 s from the baseline at the end of the study was set as the primary endpoint. Secondary endpoints included angina class, Seattle angina questionnaire scores, symptoms, and ECG changes during stress test. Patients underwent nine sessions of CSWT or corresponding sham procedure applied to all segments of the left ventricle, within 9 weeks. Endpoint assessments were performed at 6-month follow-up. The imaging substudies assessed the potential of CSWT to reduce stress-induced myocardial ischemia detected by dobutamine stress echocardiography, cardiac single-photon emission computed tomography, and cardiac magnetic resonance imaging.
Results: At two centers, 72 of the 323 screened patients were randomized in two groups (ratio 1: 1): active treatment and placebo control. Study patients were predominantly males (70.8%); the mean age of the patients was 68.4±8.3 years. Of these, 44 patients had angina Canadian Cardiovascular Society class III, and 66.7% of the patients had a history of myocardial infarction.
Conclusion: Using sham applicators, blinding study participants, investigators, and endpoints assessors to the study data as well as centralized randomization ensures rigorous methodology and low risk of bias in this large randomized controlled CSWT study.

Objective: Coronary artery ectasia (CAE) is defined as an angiographic enlargement of a portion of the coronary artery between 1.5 and 2 times the diameter of the adjacent normal coronary artery. It has been demonstrated that increased serum prolidase activity (SPA) is associated with increased collagen turnover. We aimed to analyze the relationship between CAE and serum SPA levels.
Methods: This study used a prospective case protocol design. A total of 40 consecutive patients with isolated right CAE and normal coronary arteries (23 men, 17 women; mean age, 62.4±10.8 years) were evaluated. The control group included the same number of consecutive patients with angiographically normal coronary arteries (20 men, 20 women; mean age, 63.8±11.1 years). Clinical characteristics, laboratory results, cardiovascular risk factors, and medication use were recorded. SPA was measured using a spectrophotometer. Student’s t-test, Mann–Whitney U test, chi-square test, Pearson’s and Spearman’s correlations, logistic regression analysis, and ROC curve analysis were used for statistical analysis.
Results: SPA was significantly higher in the CAE group compared with the control group (1635.2±492.0 U/L and 986.2±422.3 U/L, respectively; p<0.001). The relationship of SPA with CAE proved to be significant (r=0.512; p<0.001). SPA also served as an independent predictor of CAE (OR=1.003; 95% CI, 1.001–1.005; p=0.002). The SPA value of 1170 U/L was predictive of CAE, with a sensitivity of 85% and specificity of 60% (AUC=0.854; 95% CI, 0.763–0.944; p<0.001).
Conclusion: The activity of this enzyme was significantly correlated with CAE.

Objective: In hemodialysis (HD) patients, cardiovascular disease (CVD) is the major cause of mortality and morbidity. In atherosclerotic diseases, iron gets accumulated in the arterial wall. Hepcidin is an important hormone in iron metabolism. Furthermore, hepcidin is associated with atherosclerotic disease. Therefore, this study aims to investigate the relation of serum hepcidin-25 (SH-25) and sub-clinic atherosclerosis measured by carotid intima-media thickness (CIMT) and mortality in HD patients.
Methods: We enrolled 82 HD patients in a cross-control study. We measured SH-25 using ELISA kit and CIMT using high-resolution real-time ultrasonography. After 4 years of first assessment, we investigated the relation between all-cause and cardiovascular mortality and SH-25 and CIMT.
Results: Two patients were excluded because of renal transplantation. The survivors were younger (53.7±15.1 vs. 65.2±15.5; p<0.05) and CIMT was lower (0.83±0.2 vs. 0.95±0.2; p<0.05); however, there was no significant difference in SH-25 levels between the groups (29.1±13 vs. 32.4±22.4;p=0.767). The patients who died of CVD were significantly older (63.7±16.1 vs. 53.7±15.1; p<0.05) and had significantly higher CIMT (0.94±0.2 vs. 83±0.2; p<0.05). The SH-25 levels were statistically significantly higher in patients who died of CVD (40.3±25 vs. 29.1±13; p<0.05). Linear regression
analysis showed a positive correlation between CIMT and SH-25 in the study population and in those who died from CVD (r=0.41; p<0.05 and r=0.606; p<0.05, respectively).
Conclusion: This study suggests that hepcidin is effective in cardiovascular mortality and pathophysiology of subclinical atherosclerosis in HD patients.

Objective: To investigate the association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance (CR) in patients with cardiovascular disease in Beijing district.
Methods: In total, 325 patients were enrolled in the study, including 101 experimental group patients and 224 control group patients. The experimental group was divided into CR group (n=30) and non-CR group (n=71) according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was defined as CR and rate of 30%–100% was defined as non-CR). Genotypes, including CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*17, and ABCB1, were determined using time-of-flight mass spectrometry (Clin-TOF) and Sanger sequencing in all patients.
Results: In the experimental group, carriers of CYP2C19 heterozygous (*1/*2, n=46; *1/*3, n=7), and mutation homozygous (*2/*2, n=7; *2/*3, n=3; *3/*3, n=0) genotypes showed significantly lower ADP-induced platelet inhibition rates than noncarriers (*1/*1, n=38; p=0.035 and 0.001, respectively); the carriage of mutant CYP2C19*2 or *3 allele was significantly associated with an increased risk of CR. In contrast, carriers of ABCB1 heterozygous (TC, n=50) showed significantly lower ADP-induced platelet inhibition rates than noncarriers (CC, n=39, p=0.097), and there was no significant correlation between ABCB1 genotypes and higher CR risk.
Conclusion: The carriage of CYP2C19*2 or *3 mutant allele was significantly associated with attenuated platelet response to clopidogrel and increased CR risk. The carriage of ABCB1 mutant allele was not significantly associated with CR risk.

Objective: Cardiovascular diseases are the most important cause of mortality worldwide, particularly atherosclerosis. Recently, lncRNAs affecting atherosclerotic progression have been reported in vascular smooth muscle cells, endothelial cells, and monocytes, suggesting that lncRNAs play an important role in atherosclerosis.
Methods: In recent clinical studies, nowadays, it was determined that internal mammary bypass grafts are closest to ideal grafts in coronary artery bypass surgery. In this study, we used tissue samples taken from atherosclerotic coronary arteries and the internal mammary artery (IMA) during coronary artery bypass surgery. Using RT-PCR, we investigated the role of two lncRNAs, FENDRR and LincRNA-p21, by comparing their expression levels in coronary artery plaques and normal mammary arteries of 20 atherosclerotic patients.
Results: We found that the FENDRR and LincRNA-p21 expressions decreased by approximately 2 and 7 fold in coronary artery plaques, respectively, compared with those in IMA, which is known to have no plaque development.
Conclusion: This study was the first to use mammary artery tissues of the same patients as a control and to study FENDRR expression. Our data may provide helpful insights regarding the association of lncRNAs and atherosclerosis.

Although various cardiac monitoring methods were developed to detect subclinical arrhythmias, guidelines do not address in detail the management of subclinical atrial fibrillation and tachyarrhythmias. The European Heart Rhythm Association recently published a consensus document that addresses the clinical importance, implications, and management of device-detected subclinical atrial tachyarrhythmias. This paper comprehensively reviews the diagnostic tools to detect subclinical atrial arrhythmias and discusses the pathophysiologic link between device-detected subclinical atrial fibrillation and stroke. In this invited review, in the light of this paper and current scientific data, we aimed to summarize how to manage subclinical atrial arrhythmias.

Traditional circulating biomarkers play a fundamental role in the diagnosis and prognosis of acute myocardial infarction (AMI). However, they have several limitations. microRNAs (miRs), a class of RNA molecules that do not encode proteins, function directly at the RNA level by inhibiting the translation of messenger RNAs. Due to their significant roles in disease development, they can be used as biomarkers. Accumulating evidence has revealed an attractive role of miRs as biomarkers of AMI and its associated symptoms, including vulnerable atherosclerotic plaques, and their role in disease diagnosis, platelet activation monitoring, and prognostic outcome prediction. This manuscript will highlight the recent updates regarding the involvement of miRs as biomarkers in AMI and emphasize their value in vulnerable atherosclerotic plaque prediction and monitoring of platelet activation.