Silencing hsa_circ_0049271 attenuates hypoxia-reoxygenation (H/R)-induced myocardial cell injury via the miR-17-3p/FZD4 signaling axis.

Background: This study sought to explore the role and molecular mechanism of circ_0049271 in hypoxia-reoxygenation (H/R)-induced cardiomyocyte injury. Methods: Significantly upregulated circular ribonucleic acids (circRNAs) in Gene Expression Omnibus (GEO) data sets were identified using a Venn diagram. A H9c2 (rat cardiomyocytes) cell model of acute myocardial infarction (AMI) was induced by 1% H/R. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression levels of circ_0049271, miR-17-3p, and FZD4 in clinical blood samples and cells, and Cell Counting Kit-8 (CCK-8) was used to determine the proliferation rate of the cells in each group. Next, flow cytometry and Western blot were used to evaluate cell apoptosis. Biochemical tests and enzyme-linked immunosorbent assays (ELISAs) were then used to determine the activities/levels of the cell damage markers [i.e., creatine kinase (CK) and lactate dehydrogenase (LDH)], oxidative stress substances [i.e., malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD)], and inflammatory factors [i.e., interleukin (IL)-1ß, IL-6, and IL-8]. In addition, intermolecular interactions were verified using dual-luciferase reporter and RNA pull-down experiments. Results: Circ_0049271 was significantly upregulated in both the blood of the AMI patients and the H/R-induced H9c2 cells. The knockdown of circ_0049271 increased the cell proliferation rate, decreased the apoptosis rate, inhibited oxidative stress (ROS and MDA were upregulated, and SOD was downregulated) and inflammatory responses (IL-1, IL-6, and IL-8 were downregulated), and relieved cell damage. However, the overexpression of circ_0049271 promoted H/R-induced H9c2 cell damage. Further experiments showed that miR-17-3p was a target of circ_0049271, and miR-17-3p was negatively correlated with circ_0049271 in the AMI blood samples. Additionally, miR-17-3p was found to target FZD4. A further exploration also revealed that miR-17-3p knockdown or FZD4 overexpression reversed the effects of si-circ_0049271 on the H/R-induced H9c2 cells; that is, miR-17-3p knockdown or FZD4 overexpression promoted H/R-induced injury in the H9c2 cells. Conclusions: Circ_0049271 promoted cellular function damage (e.g., proliferation inhibition, apoptosis, oxidative stress, and inflammation) in H/R-induced H9c2 cardiomyocytes via the miR-17-3p/FZD4 signaling axis.

Utilization of Risk Scores for Coronary Heart Disease Diagnosis in Rural China.

Objective: The current study was to design a cardiovascular risk score for the diagnosis of coronary heart disease (CHD) in the rural area of China and the sensitivity and specificity of this score would be assessed. Methods: A total of 520 patients were enrolled and based on the results from coronary artery angiography, patients were divided into three groups: CHD group (coronary artery ≥50% stenosis), atherosclerosis group (coronary artery <50% stenosis) and normal groups (without stenosis). Between-group differences were evaluated and the sensitivity and specificity of cardiovascular risk score were evaluated. Results: Compared to the normal and atherosclerosis groups, patients in the CHD group were older, had higher body mass index, and more likely to be smoking and obese, and had dyslipidemia, hypertension and diabetes, and had higher cardiovascular risk score (4.05 ± 2.15 vs 2.94 ± 1.90 vs 2.54 ± 1.59). Patients in the CHD group were more likely to have cardiovascular risk scores ≥2 (90.2% CHD group vs 74.2% atherosclerosis group vs 76.1% normal group, P < 0.05). The area under the ROC was 0.673, with 95% confidence interval was 0.623-0.722 (P < 0.001), and the sensitivity and specificity were highest when the cardiovascular risk score was 4, indicating that the value of cardiovascular risk score of 4 was a good cutoff point for CHD diagnosis. Conclusion: Using cardiovascular risk score can improve CHD diagnosis which may help to reduce health disparities between rural and urban area.

Association of Etoricoxib treatment and incident hypoxia in patients with aortic dissection undergoing endovascular aortic repair.

OBJECTIVE: The current study was to evaluate the association of Etoricoxib treatment and incident hypoxia among type-B aortic dissection (AD) patients undergoing endovascular aortic repair (EVAR). METHODS: Patients undergoing EVAR were retrospectively recruited. Based on Etoricoxib use, patients were divided into the non-treated and Etoricoxib-treated groups. Baseline characteristics including demographics, laboratory parameters, characteristics of aortic computer tomography and echocardiography, medications used, and procedural characteristics were collected from the electronic health record. RESULTS: Compared to non-treated group (n = 36), prevalence of obesity and fever at baseline was higher in Etoricoxib-treated group (n = 24; P < 0.05). Mean number of neutrophils, and mean serum CRP and D-dimer levels were higher in Etoricoxib-treated group (P < 0.05). The overall incidence of hypoxia was lower in Etoricoxib-treated group (44.4% vs 33.4%, P < 0.05). Increase in neutrophils count, serum CRP and D-dimer levels was associated with incident hypoxia, with an odds ratio (OR) of 1.36 (95% confidence interval [CI] 1.07-1.65), 1.44 (95% CI 1.12-1.78) and 1.25 (95% CI 1.01-1.47) respectively. In unadjusted model, Etoricoxib use was associated with a 44% lower odds of incident hypoxia. After adjustment for inflammatory markers, the association between Etoricoxib and incident hypoxia was non-significant, with OR of 0.95% and 95% CI of 0.78-1.06. CONCLUSION: Compared to patients who did not receive Etoricoxib during hospitalization, those treated with Etoricoxib had lower incidence of hypoxia, which might be attributed to its anti-inflammatory effects.

Association of hyperuricemia and hypertension phenotypes in hypertensive patients without uric acid lowering treatment.

BACKGROUND: Current study was to evaluate the association of hypertensive and hypertension phenotypes in hypertensive populations. METHODS: Patients with primary hypertension and without any uric acid (UA)-lowering treatment were enrolled. Baseline characteristics including office blood pressure (OBP), 24 h ambulatory blood pressure (ABP), and serum UA (SUA) were measured. According to SUA, patients were divided into normal SUA and hyperuricemia groups. Based on OBP and 24 h-ABP, hypertension phenotypes were classified as controlled hypertension (CH), white-coat uncontrolled hypertension (WCUH), masked uncontrolled hypertension (MUCH), and sustained uncontrolled hypertension (SUCH). RESULTS: Compared to patients with normal SUA (n = 336), patients with hyperuricemia (n = 284) were older and more likely to be men, obese, physically inactive, and have a higher prevalence of diabetes. C-reactive protein (CRP) level was higher in patients with hyperuricemia. The prevalence of CH, WCUH, and MUCH was similar between these two groups. However, the prevalence of SUCH was higher in patients with hyperuricemia than patients with normal SUA. Linear regression analysis indicated that increased SUA was significantly associated with 24 h-systolic BP and daytime-systolic BP. Normal SUA was served as the reference group, and presence of hyperuricemia was associated with higher odds of SUCH (odds ratio 1.46 and 95% confidence interval 1.27-1.93) after adjusted for potential covariates including age, male gender, obesity, diabetes, CRP, and antihypertensive drugs. CONCLUSION: In hypertensive patients without UA-lowering treatment, presence of hyperuricemia was associated with higher odds of SUCH. Future studies are needed to evaluate whether lowering SUA can help to improve 24 h-ABP control.

Clinical Characteristics and Prognosis of Young Patients with Coronary Heart Disease.

BACKGROUND The objective of this study was to investigate the clinical characteristics and prognosis of coronary heart disease (CHD) in young patients. MATERIAL AND METHODS We included 972 CHD patients (≤50 years old) with coronary artery stenting who were prospectively enrolled and followed for 1 year. Clinical characteristics, risk factors, and predictors of outcomes were evaluated. RESULTS The prevalence of current smoker, hypertension, diabetes mellitus, dyslipidemia and positive family history of CHD were 18.9%, 34.3%, 14.5%, 4.4%, and 44.2%, respectively. Most of the patients underwent coronary stenting due to stable angina (48.8%) and unstable angina (UA; 48.1%). After 1-year follow-up, 64 patients (6.6%) experienced clinical outcomes and the most common event was UA (n=56). Compared to patients without clinical outcomes, those with outcomes were more likely to be male, have higher systolic blood pressure, more likely to have hypertension and diabetes mellitus, and more likely to be presented as unstable angina. Multivariate regression analysis showed only age (hazard ratio [HR]: 1.12 and 95% confidence interval [CI]: 1.07-1.26), smoking (HR: 1.15 and 95% CI: 1.06-1.23), presence of hypertension (HR: 1.19 and 95% CI: 1.13-1.31), and diabetes mellitus (HR: 1.16 and 95% CI: 1.09-1.28), more vessels with stenosis (HR: 1.27 and 95% CI: 1.20-1.48) and presented with acute coronary syndrome (HR: 1.35 and 95% CI: 1.21-1.55) were independently associated with clinical outcomes. CONCLUSIONS Most of the young (≤50 years of age) CHD patients had poor management of risk factors and better controlling these risk factors would be helpful for the primary and secondary prevention of premature CHD in Guangdong province.

Impact of concurrent right ventricular myocardial infarction on outcomes among patients with left ventricular myocardial infarction.

To compare in-hospital outcomes between left ventricular myocardial infarction (LVMI) patients with and without right ventricular myocardial infarction (RVMI). Patients with acute ST-segment elevation MI (STEMI) undergoing primary percutaneous coronary intervention (PCI) were enrolled and divided into LVMI with and without RVMI groups. Between-group differences and in-hospital outcomes were compared. Compared to patients without RVMI, patients with RVMI were more likely to be male, have higher body mass index, serum levels of C-reactive protein (8.9 ± 2.4 vs 6.2 ± 2.1 mg/dL), B-type natriuretic peptide (1295 ± 340 vs 872 ± 166 pg/mL) and cardiac troponin-I (8.6 ± 2.9 vs 5.2 ± 2.1 ng/mL), and have diabetes (36.3% vs 3.4%) and dyslipidemia (53.4% vs 48.1%). Patients with RVMI had lower left and right ventricular ejection fraction (50.5 ± 5.6% vs 53.4 ± 3.8% and 33.6 ± 2.9% vs 45.7 ± 2.0%), but had higher mean pulmonary artery pressure (30.6 ± 3.3 vs 23.8 ± 3.1 mm Hg). Compared to patients without RVMI, patients with RVMI had higher odds of in-hospital all-cause mortality (4.1% vs 1.0%) and new onset acute heart failure (3.4% vs 1.0%). After adjusted for confounding factors, LVMI with RVMI remained independently associated with composite outcomes, with odds ratio 1.66 (95% confidence interval 1.39-2.04). Compared to isolated LVMI patients, those with concomitant RVMI have higher odds of in-hospital complications, particularly all-cause mortality and new onset acute heart failure.

Effects of switching ticagrelor to clopidogrel on cardiovascular outcomes in patients with acute coronary syndrome.

Present study was to evaluate whether switching ticagrelor to clopidogrel would impact platelet reactivity and cardiovascular outcomes in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI).A total of 202 ACS patients after PCI were enrolled and prescribed ticagrelor. Before discharge, 138 (68%) patients were switched to clopidogrel. Peripheral blood was obtained before switching and at 48 hours after switching to measure platelet reactivity. Patients were followed for 30 days to evaluate cardiovascular events.Compared to ticagrelor group, patients in clopidogrel group were more likely to be male (69.6% vs 65.6%), smokers (34.1% vs 31.3%) and had higher prevalence of hypertension (75.4% vs 71.9%). The frequency of right coronary artery lesion was significantly higher in ticagrelor group (34.4% vs 30.4%). There were no significant differences in baseline platelet reactivity (37.6 ±â€Š5.2% vs 38.4 ±â€Š4.9%). Forty-eight hours after switching to clopidogrel, platelet reactivity in clopidogrel group was significantly higher (46.3 ±â€Š5.6% vs 38.1 ±â€Š5.0%, P <.05). Patients in clopidogrel group had significantly higher incidence of cardiovascular events (3.6% vs 1.6%, P <.05). However, after further adjusted for platelet reactivity at 48 hours of switching, clopidogrel switching was not significantly associated with composite outcomes, with hazard ratio 1.08 (95% confidence interval 0.98-1.21, P = .063), indicating that platelet reactivity was a critical mediator between antiplatelet drug switching and cardiovascular outcomes.ACS patients after PCI treatment, early switching ticagrelor to clopidogrel results in increased platelet reactivity and higher incidence of short-term cardiovascular events.

Association of serum total cholesterol and left ventricular ejection fraction in patients with heart failure caused by coronary heart disease.

INTRODUCTION: The aim was to evaluate the association of serum total cholesterol (TC) level and left ventricular ejection fraction (LVEF) in patients with heart failure (HF) caused by coronary heart disease (CHD). MATERIAL AND METHODS: A total of 236 participants were enrolled. Participants were divided into severely reduced (≤ 35%) and moderately reduced (> 35%) LVEF groups and the between-group difference was evaluated. Multivariate regression analysis was used to evaluate the association between LVEF and parameters of interest. Linear regression analysis was applied to analyze the odds ratio of per 1-SD increase in serum TC level for LVEF change. RESULTS: Mean age was 57.3 years and males accounted for 58.1%. Mean serum TC level was 4.6 mmol/l, albumin (ALB) 33.6 g/l, and C-reactive protein (CRP) 11.4 mg/l. Mean LVEF was 38.3%. Compared to high-reduced LVEF group, participants in moderate-reduced LVEF group had significantly higher TC (4.8 ±0.9 mmol/l vs. 4.4 ± 0.7 mmol/l) and ALB (35.8 ±6.7 g/l vs. 31.4 ±6.0 g/l) but lower CRP (9.6 ±4.7 mg/l vs. 14.2 ±7.0 mg/l) levels (p < 0.05 for all comparisons). Increased TC and ALB levels were associated with higher LVEF, and increased CRP level was associated with lower LVEF. After adjusted for CRP, although per 1-SD increase in TC level was still associated with an increment in 4 % in LVEF, it did not achieve achieve statistic significance. CONCLUSIONS: In patients with HF caused by CHD, higher serum TC level appeared to be associated with higher LVEF, which might be associated with systemic inflammation improvement.

Spironolactone is superior to hydrochlorothiazide for blood pressure control and arterial stiffness improvement: A prospective study.

The present study is to investigate whether spironolactone is better than hydrochlorothiazide (HCTZ) for blood pressure (BP) control and arterial stiffness improvement. Five-hundred-sixty-six uncontrolled hypertensive patients with 2 different classes of antihypertensive medications treatment were enrolled. Spironolactone or HCTZ was randomly prescribed for 4 weeks. Carotid-femoral pulse wave velocity (cf-PWV) was measured at baseline and after 4 weeks' of spironolactone or HCTZ treatment. Between-group differences were evaluated, and logistic regression analysis was performed to evaluate the association of cf-PWV increase and incident resistant hypertension. No significant differences in baseline characteristics were observed between spironolactone and HCTZ groups. After 4 weeks' treatment, both systolic BP and cf-PWV were reduced more profoundly in spironolactone group versus HCTZ group (P < .05). Pearson and Spearman correlation analysis showed that age, diabetes mellitus, and HCTZ were positively correlated with cf-PWV, while spironolactone was negatively with cf-PWV. Logistic regression analysis indicated that per 1-standard deviation increase in cf-PWV was associated with 92% higher incidence of resistant hypertension. After adjusted for spironolactone, no significant association between cf-PWV increase and incident resistant hypertension was observed, indicating that the adverse effect of arterial stiffness on resistant hypertension development might be reversed by spironolactone treatment. In summary, uncontrolled hypertensive patients with spironolactone treatment appear to have better BP control and arterial stiffness improvement.

Effects and mechanism of moderate aerobic exercise on impaired fasting glucose improvement.

BACKGROUND: Exercise is beneficial for blood glucose metabolism. However, whether moderate aerobic exercise could improve impaired fasting glucose is unknown. And the mechanism is also needed to investigate. METHODS: A cross-sectional research was performed and 120 participants with impaired fasting glucose (IFG) were randomly assigned into active and controlled groups. Briefly, participants in active group were required to take moderate aerobic exercise at least 30 min for five times per week, whereas in controlled group, participants were also advised to take exercise but not mandatorily required the same degree as that of active group. At baseline and 3 month's follow-up, laboratory and demographic variables were compared. RESULTS: At baseline, no significant between-group differences were observed. Generally, leukocyte ROCK2 activity in the active and controlled groups were 58.7 ± 6.0 mg/mL and 60.2 ± 7.3 mg/mL, and daily average exercise time at baseline in both groups was extremely little, with 5.2 ± 3.8 min and 5.9 ± 3.5 min, respectively. After 3 months' follow-up, 52 and 56 participants in the active and controlled groups completed the whole program. Compared to baseline, leukocyte ROCK2 activity and daily average exercise time were improved in both groups. Nonetheless, compared to the controlled group, leukocyte ROCK2 activity was reduced more profoundly and the daily average exercise time was longer in the active group (37.5 ± 6.3 min versus 18.3 ± 7.2 min, p < 0.05). Moreover, the percentage of IFG in the active group was decreased more prominently than the controlled group (76.9% versus 82.1%, p < 0.05). Multivariate regression analyses revealed that exercise time and leukocyte ROCK2 activity was significantly associated with IFG, with OR of 0.836 (active group versus controlled group, 95% CI 0.825-0.852, p < 0.05) in exercise time, and 1.043 (controlled group versus active group, 95% CI 1.021-1.069, p < 0.05) in leukocyte ROCK2 activity. In addition, exercise time was significantly associated with leukocyte ROCK2 activity, with OR of 0.822 (active group versus controlled group, 95% CI 0.818-0.843, p < 0.05). CONCLUSION: In subjects with IFG, increased daily average exercise time is beneficial for improving fasting blood glucose metabolism, and the mechanism may be associated with its effects on attenuating leukocyte ROCK2 activity.

Increased Hs-CRP/adiponectin ratio is associated with increase carotid intima-media thickness.

BACKGROUND: High sensitivity C-reactive protein (Hs-CRP) and adiponectin (APN) are two critical cytokines and exert inverse effects on atherosclerosis initiation and progression. The purpose of our study was to investigate the value of Hs-CRP and ANP ratio (Hs-CRP/APN ratio) on evaluating atherosclerosis progression. METHOD: One hundred sixty consecutive participants underwent carotid intima-media thickness (CIMT) measured by ultrasound were enrolled and drawn fasting blood samples for plasma levels Hs-CRP and APN, serum levels of lipid profiles and fasting blood glucose evaluation. Other anthropometrics and clinical status were collected by questionnaire. All participants were divided into 4 groups according to the baseline Hs-CRP/APN ratio and underwent CIMT measurement every 6 months. CIMT increment and composite cardiovascular endpoints were compared after 24 months' follow-up. RESULTS: At baseline, body mass index (BMI), smoking, diabetic mellitus, usage of statins, Hs-CRP and APN independently correlated with Hs-CRP/APN ratio as analyzed by spearman rank correlation. Smoking, serum level of LDL-C, plasma level of Hs-CRP and Hs-CRP/APN ratio were positively correlated with CIMT while usage of statins and plasma level of APN were negatively correlated with CIMT as analyzed by multiple linear regression analysis. After 24 months' follow-up, the progression of CIMT was the most prominent in the fourth quartile of baseline Hs-CRP/APN ratio. In addition, the incidence of composite cardiovascular endpoint was also higher in the fourth quartile as compared to the other 3 lower quartiles. CONCLUSION: Hs-CRP/APN ratio was a useful predictor to discriminate subjects who were at increased risk of atherosclerosis progression.

Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after stent placement.

BACKGROUND: Lipoprotein associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular risk prediction. Whether increased Lp-PLA2 level is associated with re-stenosis after stent-placement is unclear. METHODS: Totally 326 participants eligible for stent-placement were enrolled and divided into two groups according to baseline Lp-PLA2 levels (named normal and elevated groups). Baseline characteristics and clinical outcomes were compared between normal and elevated groups. The relationships between Lp-PLA2 and other risk factors with re-stenosis were evaluated. RESULTS: Only the between-group difference of Lp-PLA2 was significant (123.2 ± 33.6 ng/mL vs 336.8 ± 85.4 ng/mL, P < 0.001) while other demographic and clinical characteristics between these two groups were comparable. Approximately 55.1% and 58.5% of participants in normal and elevated groups presented with acute coronary syndrome, and the percentage of tri-vessels stenoses was significantly higher in elevated group (40.8% vs 32.1%, P = 0.016). Nearly 96.0% and 94.0% of participants in normal and elevated Lp-PLA2 groups were placed with drug-eluting stents, and the others were with bare-metal stents. After 1 year's follow-up, the incidence of clinical end-points was comparable (13.3% vs 15.4%, P = 0.172). Nevertheless, the incidence of re-stenosis was marginally higher in elevated Lp-PLA2 group (8.5% versus 4.6%, P = 0.047). With multivariate analysis, after adjustment for other risk factors, Lp-PLA2 remained an independent predictor for re-stenosis with a hazard ratio of 1.140. No synergistic effect between Lp-PLA2 and other risk factors for re-stenosis was found. CONCLUSION: Increased Lp-PLA2 level is associated with an increased risk of re-stenosis. Lp-PLA2 assessment may be useful in predicting subjects who are at increased risk for re-stenosis.

[Effects of Sini decoction on the expressions of Smad2 and Smad7 in isoproterenol induced myocardial fibrosis rats].

OBJECTIVE: To explore the effects of Sini Decoction (SD) on the expressions of Samd2 and Smad7 isoproterenol (Iso) induced myocardial fibrosis rats. METHODS: Totally 19 Wistar rats were randomly divided into 3 groups, i.e., the control group, the model group, and the SD group. Iso was injected to rats in the model group and the SD group, while normal saline was injected to rats in the control group. SD was given to rats in the SD group by gastrogavage, while normal saline was administered to rats in the control group and the model group by gastrogavage. Four weeks later Masson staining and electron microscopic analysis were performed in each group. The protein and mRNA expressions of Smad2 and Smad7 were detected using immunohistochemical assay and RT-PCR. RESULTS: Masson staining showed the IOD value of the myocardial collagen fiber was 9 303 in the model group, 2 459 in the SD group, and 4 224 in the control group, indicating the myocardial fibrosis was more obvious in the model group than in the SD group and the control group. The IOD value of Smad2 protein was 20 275 and the mRNA IOD of Smad2 protein was 0. 919 in the model group, while they were respectively 9 949 and 0. 561 in the SD group, indicating the protein and mRNA expressions of Smad2 were obviously higher in the model group than in the SD group (P < 0.05). The IOD value of Smad7 protein was 25 667 and the mRNA IOD of Smad7 protein was 0.222 in the model group, while they were respectively 93 147 and 0. 412 in the SD group, indicating the protein and mRNA expressions of Smad7 was obviously lower in the model group than in the SD group (P < 0.05). CONCLUSION: SD could effectively inhibit Iso induced myocardial fibrosis, and its mechanism may be associated with down-regulating the expression of Smad2 and up-regulating the expression of Smad7.