Sanwei sandalwood decoction ameliorates acute ischemiareperfusion injury in rats by modulating myocyte electrophysiological characteristics.

Sanwei sandalwood decoction (SWTX) is a classical Chinese medicine formula and clinically effective treatment for coronary heart disease, including myocardial ischemia/reperfusion (I/R) injury. Because the treatment mechanism of SWTX in I/R injury remains obscure, we intended to analyze the potential cardioprotective effects of SWTX in rats with myocardial I/R injury. Our research revealed that SWTX prolonged ventricular conduction time in a dose-dependent manner. While SWTX significantly delayed left ventricular signal conduction velocity, it had no effect on left atrial conduction velocity. Under sinus conditions, low SWTX concentrations reduced left ventricular conduction dispersion, while high concentrations increased conduction dispersion. SWTX also prolonged the QRS interval, APD30/50/90, and ERP. In whole-cell patch clamp experiments on myocytes, Ito and Ikr were inhibited by SWTX. While SWTX had no effect on INa, the activation curve for Nav1.5 was left-shifted. Finally, SWTX reduced the probability of ventricular fibrillation and suppressed early and late depolarization in an acute I/R injury rat model. These findings shed light on the mechanism by which SWTX alleviates myocardial I/R injury.

Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

RESEARCH QUESTION: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity? DESIGN: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo. RESULTS: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%). CONCLUSIONS: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

Perfluorodecanoic acid induces meiotic defects and deterioration of mice oocytes in vitro.

Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 µM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration.

[Effects of Mongolian medicine Shaosha-7 on myocardial ischemia/ reperfusion injury of rats].

Objective: To investigate the effects of Shaosha-7 in rats with myocardial ischemia-reperfusion injury and its mechanisms. Methods: male SD rats were divided into sham operation group (n=10), myocardial ischemia-reperfusion injury group (n=10), low, medium and high dose of Shaosha-7 groups (n=10), and positive drug group (n=10). The rats of Shaosha-7 (low, medium and high dose) groups were treated with Shaosha-7 at the doses of 0.4, 0.8 and 1.6 g/kg respectively, once a day for 15 days. The rats of positive drug group were treated with 0.3 g/kg Danshen, once a day for 15 days. The rats of the sham operation group and myocardial ischemia-reperfusion injury were treated with 2 ml/100 g distilled water, once a day for 15 days. After 15 days, the rats of the model group and the treatment group underwent thoracotomy and ligation of coronary artery for 30 minutes, then thoracic cavity was closed after reperfusion. Rats in six groups were executed electrocardiographic examination and their hearts were taken for Hematoxylin-Eosin (HE) staining and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to observe infarct area and myocardial pathological changes. The contents of cTnI, CK-MB, LDH, MDA, SOD, GSH-Px, TNF-α, IL-18, IL-6 and IL-1 ß in serum were detected by ELISA. The expression of NF-кB was detected by immunohistochemistry. Results: Compared with the sham operation group, the infarct size, the levels of cTnI, CK-MB, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1ß and NF-кB were increased and the content of SOD were decreased in rats with myocardial ischemia-reperfusion injury. Compared with the rats with myocardial ischemia-reperfusion injury, Shaosha-7 improved the arrhythmia and pathological changes, reduced the infarct area, decreased the contents of cTnI, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1 ß, increased the content of SOD, decreased the expression of NF-кB. Conclusion: Mongolian medicine Shaosha-7 can effectively alleviate myocardial ischemia-reperfusion injury in rats. This study provides a theoretical basis for the treatment of myocardial ischemia-reperfusion (I/R) injury with Shaosha-7.

Serum parathyroid hormone levels in patients with chronic right heart failure.

Parathyroid hormone (PTH) is a novel cardiovascular biomarker which is particularly useful for detection and assessment of heart failure (HF). However, previous studies examining PTH in heart failure have primarily focused on left HF; thus, the relationship between PTH and right HF remains unclear. The aim of the present study was to evaluate the serum PTH levels in patients with chronic right HF. A total of 154 patients with chronic right HF were enrolled in the present study. A binary logistic regression analysis model was used to assess the independent predictive value of PTH levels in chronic right HF. Partial correlative analysis was used to demonstrate the relevance of PTH levels on the parameters of assessment of right heart function. A multiple linear regression analysis model was used to evaluate the independent factors of PTH levels in patients with right HF. The results showed that the serum PTH levels in the right HF group were significantly higher compared with the control group. After adjusting for predictors of right HF, serum PTH levels were associated with right HF with an odds ratio of 1.066 (95% confidence interval: 1.030-1.102, P<0.001. Serum PTH levels were independently correlated with plasma N-terminal pro-B-type natriuretic peptide levels, right ventricular end-diastolic diameter and severity of lower extremity edema (all P<0.05). Therefore, based on the results of the present study, PTH may be a useful biomarker for detection and assessment of right HF.

Wnt11 preserves mitochondrial membrane potential and protects cardiomyocytes against hypoxia through paracrine signaling.

We investigated the effect of Wnt11 on mitochondrial membrane integrity in cardiomyocytes (CMs) and the underlying mechanism of Wnt11-mediated CM protection against hypoxic injury. A rat mesenchymal stem cell (MSC) line that overexpresses Wnt11 (MSCWnt11 ) and a control cell line transduced with empty vector (MSCNull ) were established to determine the cardioprotective role of Wnt11 in response to hypoxia. Mitochondrial membrane integrity in MSCWnt11 cells was assessed using fluorescence assays. The role of paracrine signaling mediated by vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), and insulin-like growth factor 1 (IGF-1) in protecting CMs against hypoxia were investigated using cocultures of primary CMs from neonatal rats with conditioned medium (CdM) from MSCWnt11 . MSCWnt11 cells exposed to hypoxia reduced lactate dehydrogenase release from CMs and increased CM survival under hypoxia. In addition, CMs cocultured with CdM that were exposed to hypoxia showed reduced CM apoptosis and necrosis. There was significantly higher VEGF and IGF-1 release in the MSCWnt11 group compared with the MSCNull group, and the addition of anti-VEGF and anti-IGF-1 antibodies inhibited secretion. Moreover, mitochondrial membrane integrity was maintained in the MSCWnt11 cell line. In conclusion, overexpression of Wnt11 in MSCs promotes IGF-1 and VEGF release, thereby protecting CMs against hypoxia.

Adsorption of Cadmium Ions from an Aqueous Solution on a Highly Stable Dopamine-Modified Magnetic Nano-Adsorbent.

Magnetic nanomaterials were functionalized with dopamine hydrochloride as the functional reagent to afford a core-shell-type Fe3O4 modified with polydopamine (Fe3O4@PDA) composite, which was used for the adsorption of cadmium ions from an aqueous solution. In addition, the effects of environmental factors on the adsorption capacity were investigated. Furthermore, the adsorption kinetics, isotherm, and thermodynamics of the adsorbents were discussed. Results revealed that the adsorption of cadmium by Fe3O4@PDA reaches equilibrium within 120 min, and kinetic fitting data are consistent with the pseudo-second-order kinetics (R2 > 0.999). The adsorption isotherm of Cd2+ on Fe3O4@PDA was in agreement with the Freundlich model, with the maximum adsorption capacity of 21.58 mg/g. The thermodynamic parameters revealed that adsorption is inherently endothermic and spontaneous. Results obtained from the adsorption-desorption cycles revealed that Fe3O4@PDA exhibits ultra-high adsorption stability and reusability. Furthermore, the adsorbents were easily separated from water under an enhanced external magnetic field after adsorption due to the introduction of an iron-based core. Hence, this study demonstrates a promising magnetic nano-adsorbent for the effective removal of cadmium from cadmium-containing wastewater.

Coronary artery anatomy in peri-crux cordis area on computed coronary tomography angiography.

BACKGROUND: The peri-crux area is an anatomical structure of the heart. Unfortunately, important information on this area mainly derives from autopsy heart with a small, under-representative sample size, resulting in limited clinical applications. Furthermore, little has been done to standardize the definition of the peri-crux area on coronary computed tomography angiography (CCTA) images or to investigate coronary artery anatomy wherein potential values are attracting experienced inventional cardiologists in terms of the revascularization strategies. The current study aimed to identify the peri-crux cordis area and to observe coronary artery anatomical distributions in this area on CCTA. METHODS: A total of 1,006 consecutive patients undergoing CCTA exams were enrolled. We delineated the peri-crux cordis area based on the posterior interatrial sulcus, posterior interventricular sulcus (PIS), left and right posterior atrioventricular groove on the diaphragmatic surface of the heart. Then we observed the coronary artery distributions in the peri-crux cordis area in different sexes. RESULTS: We have defined the peri-crux cordis area according to the anatomical landmarks on the diaphragmatic surface of the heart on CCTA images. We have observed 8 coronary artery distributions in the peri-crux cordis area. Right dominance has 4 types (types 1-4); left, 1 type (type 0) and balanced, 3 types (types 5-7). Out of the 1,006 cases, the type 1 is commonest with 834 cases (82.9%). There are no statistically significant differences in terms of coronary dominances and coronary artery distributions in the peri-crux cordis area between sexes (P>0.05). CONCLUSIONS: We have defined the peri-crux cordis area utilizing the anatomical landmarks of the heart on CCTA images, where 8 types of coronary artery distributions have been identified. The current study may provide interventional cardiologists with useful information on recognition of coronary artery dominance, use of collateral channels for revascularization of chronic total occluded lesions, and evaluation of prognosis in patients with coronary artery disease (CAD).

Comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation catheter ablation using robotic magnetic navigation system.

BACKGROUND: No data exist on comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation (AF) ablation using robotic magnetic navigation system (MNS), respectively. METHODS: About 151 AF patients were prospectively enrolled and divided into paroxysmal AF group (n = 102) and persistent AF group (n = 49). Circumferential pulmonary vein antrum isolation (CPVI) was performed in all patients. Linear ablation at the left atrial roof and mitral isthmus was performed in patients with persistent AF in addition to CPVI. The procedural time, X-ray exposure time, acute and long-term success rates of CPVI, and procedure-related complications were analyzed. The AF recurrence rates in the two groups were compared during 1 year, and Cox regression was used to analyze the recurrence risk factors. RESULTS: The acute success rates of CPVI in the two groups were 98.04% and 97.96%, respectively. There were no significant differences in the procedural time, X-ray exposure time, and ablation time between the two groups (P > 0.05). No serious complications appeared in either group. The AF ablation success rates were 70.6% and 57.1% for the paroxysmal and persistent groups respectively at 12-month follow-up (P = 0.102). AF duration and coronary heart disease prior to ablation were associated with the higher AF recurrence in patients with persistent AF. CONCLUSION: Ablation using MNS is effective and safe both in patients with paroxysmal and persistent AF. AF duration and coronary heart disease prior to ablation are two independent risk factors of AF recurrence in patients with persistent AF postoperatively.

Effects of remote ischemic post-conditioning on platelet activation of AMI patients.

The recovery of ischemic myocardium blood perfusion is the main treatment option for acute myocardial infarction (AMI). However, this treatment option has multiple side effects that directly affect the quality of life of the patients. The activation of platelet function plays an important role in the occurrence, development and treatment of AMI. The aim of the present study was to analyze the effects of remote ischemic post-conditioning on platelet activation of AMI patients with primary PCI treatment and clinical prognosis. A total of 71 patients with AMI were treated with primary percutaneous coronary intervention (PCI). They were randomly divided into control group (n=34) and observation group (n=37). The patients in the observation group were treated with remote ischemic post-conditioning. Further, flow cytometer was used to detect the platelet alpha granule membrane glycoprotein (CD62P) and the percentages of activated IIb/IIIa (PAC-1). The maximum platelet aggregation rate induced by adenosine diphosphate (ADP) and arachidonic acid (AA) was measured by light transmittance aggrometer. The incidence of major adverse cardiac events (MACE) was compared between the two groups during the follow-up period of 6 months. The percentage of CD62P (24 h after PCI) in the observation group was significantly lower than control group (P<0.05). Further, the incidence of MACE in the observation group was also lower than that of the control group (P<0.05). Remote ischemic post-conditioning could reduce the incidence of MACE in patients with AMI after primary PCI treatment. Moreover, the above observation may be related to the improvement of platelet CD62P activation.

Comparison of the Effects of Ticagrelor and Clopidogrel on Inflammatory Factors, Vascular Endothelium Functions and Short-Term Prognosis in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Emergency Percutaneous Coronary Intervention: a Pilot Study.

BACKGROUND/AIMS: Acute ST-segment elevation of myocardial infarction (STEMI) is the most severe type of acute coronary syndrome (ACS). Particular attention has been focused on studying the pathogenesis of STEMI, and how to prevent thrombosis, reduce inflammatory reaction, stabilize plaques and improve vascular endothelial functions to preserve the survived myocardium. This study aimed to compare the anti-inflammatory endothelium-protective effects, clinical prognosis, and relevant bleeding risks of ticagrelor versus clopidogrel in patients with STEMI who underwent urgent percutaneous coronary intervention (PCI) and provide certain experimental evidence and a theoretical basis for the selection of safe and effective drugs and their proper dosage, thereby further guiding clinical medication. METHODS: We sequentially enrolled 193 patients (104 males and 89 females) admitted to hospital due to acute STEMI. These patients underwent urgent PCI between December 2013 and May 2015 and met the inclusion criteria. They were assigned (1: 1) into two groups according to different treatments, 97 patients in the ticagrelor group (treatment group), and 96 patients in the clopidogrel group (control group). Levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and endothelial cell-specific molecule 1 (ESM-1) taken at admission and 24 h, 4 days, and 7 days after administration, as well as the correlation between the levels of IL-6, hs-CRP, and ESM-1, were determined in the two groups. At the same time, the effects of treatment with ticagrelor and clopidogrel on the efficacy endpoint events (ischemic and safety) were explored. RESULTS: No statistically significant difference was found in the levels of hs-CRP, IL-6, or ESM-1 at admission between the two groups (P> 0.05); Their levels were significantly elevated 24 h after administration, with statistical differences between two groups (P< 0.05). Furthermore, a downward trend with statistically significant differences was found on Day 4 and Day 7 (P< 0.05); ESM-1 levels increased along with increases of hs-CRP and IL-6 levels, indicating ESM-1 was positively correlated with hs-CRP (r=0.523, P< 0.001) and IL-6 (r=0.431, P< 0.001); and the occurrence rates of ischemic endpoint events at 30 days were lower in the treatment group than in the control group. The occurrence of safety endpoint events was higher than in the control group; however, no statistically significant difference was found (P> 0.05). CONCLUSIONS: Compared with clopidogrel, ticagrelor appears to rapidly reduce the prevalence of inflammatory reactions and stabilize the functions of vascular endothelium to improve the stability of atherosclerotic plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding in patients with acute STEMI receiving urgent PCI. This renders it a potential drug for clinical practice. At the same time, measurement of ESM-1, a new biological marker for vascular endothelial function disorder, could possibly become a simple, effective, and practical new method for clinical evaluation of risk stratification of patients with acute STEMI at admission.

Establishing age and sex dependent upper reference limits for the plasma lipoprotein (a) in a Chinese health check-up population and according to its relative risk of primary myocardial infarction.

BACKGROUND: Though lipoprotein (a) (Lp (a)) has been considered as a risk factor for coronary artery disease, there is a lack of cutoff values of Lp (a) for Chinese Han ethnicity. METHODS: We included 1 population for health check-ups. Lp (a) percentile distributions were analyzed and its cutoff for Chinese Han ethnicity was also proposed according to the its relative risk of myocardial infarction. RESULTS: Lp (a) distributions differed between sexes, and were highly skewed towards low concentrations with a long tail towards the highest ones. The relative risks of elevated Lp (a) concentrations for myocardial infarction had an inflection in Chinese Han ethnic at the 8th decile, corresponding to 167 mg/l, where the risk was prone to be increased. In terms of Lp (a) median concentrations, per higher age quantile (5-y interval) was associated with a significant increase of 3.2 mg/l and females were on average 19.75 mg/l higher than males with a significant difference. CONCLUSIONS: We proposed Lp (a) < 170 mg/l after rounding as cut-off values for Chinese Han ethnicity. Effects of age and sex on Lp (a) concentrations were also noted. Prospective validation of these cutoff values is critically important in Chinese Han ethnicity.

Impact of C-reactive protein on long-term mortality in acute myocardial infarction patients with diabetes and those without.

BACKGROUND: Little is known about the relationship between C-reactive protein (CRP) and long-term mortality after acute myocardial infarction (AMI) in diabetic patients. The current study aimed to examine whether CRP levels are associated with for long-term all-cause, cardiovascular, and cardiac mortality in AMI patients with diabetes and those without separately. METHODS: The cohort study included 663 diabetic and 1853 non-diabetic patients with AMI. The median follow-up time was 1045 days (2.9 years). RESULTS: According to the median concentration of serum CRP (8.95 mg/l), the patients were divided into two groups. The low CRP level group (<8.95 mg/l) served as a reference. In diabetic patients with AMI, the adjusted hazard ratios (HRs) for long-term all-cause, cardiovascular, and cardiac mortality were 1.62 (P = 0.027), 1.91 (P = 0.008), and 2.08 (P = 0.007), respectively. In non-diabetic patients with AMI, the adjusted hazard ratios (HRs) for long-term all-cause, cardiovascular, and cardiac mortality were 1.72 (P < 0.001), 1.8 (P < 0.001), and 1.78 (P = 0.001), respectively. CONCLUSIONS: Regardless of whether patients had diabetes or not, CRP value is an independent predictor of long-term, all-cause, cardiovascular, and cardiac mortality after AMI.

Impact of serum albumin levels on long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction.

BACKGROUND: To evaluate the association of serum albumin (SA) with long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction (AMI). METHODS: The cohort study enrolled 2305 patients with first-onset AMI. The median follow-up was of 1088days (3years). Impacts of SA on long-time mortality after AMI were determined using multivariate Cox proportional hazard regression analysis with backward selection. RESULTS: The patients were divided into three categories by SA tertiles (≤3.62, 3.63-4.08, >4.08g/dl). High tertile group was used as reference, the adjusted HRs for all-cause death were 1.21 (P=0.338) and 1.74 (P=0.003) for intermediate and low tertile, respectively (p-for-trend=0.001); The equivalent values for cardiovascular death were 1.13 (P=0.588) and 1.64 (P=0.022), respectively (p-for-trend=0.009); The corresponding values for cardiac death were 1.07 (P=0.806) and 1.59 (P=0.048), respectively (p-for-trend=0.022). Moreover, adjusted HRs per 1-g/dl decrease in SA concentrations were 1.66 (P=0.001) for all-cause death, 1.47 (P=0.024) for cardiovascular death, and 1.61 (P=0.012) for cardiac death. CONCLUSIONS: Low SA level (≤3.62g/dl) on admission was an independent predictor of long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset AMI. There was a dose-response relationship between decreased SA concentrations and increased long-term all-cause, cardiovascular, and cardiac mortality.

Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation-induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2.

Baicalin, a flavonoid glycoside separated from Scutellaria baicalensis, has cardioprotection against ischaemia/reperfusion (I/R) injury. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is considered as an endogenous protective mechanism against I/R injury depending on its anti-oxidant and anti-apoptotic characteristics. The present study demonstrates whether ALDH2 contributes to the cardioprotection of baicalin against hypoxia/reoxygenation (H/R)-inudced H9c2 cardiomyocytes injury. Our results observed that H/R treatment resulted in a significant decrease in cells viability and obvious increases in caspase-3 activity and apoptosis rate in H9c2 cells, while these alterations were evidently reversed by baicalin pretreatment. Simultaneously, baicalin mitigated H/R-induced the decreases in the levels of ALDH2 mRNA and protein as well as the activity of ALDH2 in H9c2 cells. However, we found that daidzin, an ALDH2 antagonist, remarkably attenuated baicalin-elicited inhibitory action on H/R-induced the downregulation of cells viability and Bcl-2 protein expression, and the upregulations of caspase-3 activity, apoptosis rate, cytochrome c and Bax proteins expressions in H9c2 cells. In addition, baicalin reversed H/R-induced oxidative stress as evidenced by the downregulation of malondialdehyde (MAD) and 4-hydroxy aldehydes (4-HNE) levels, the inhibition of endogenous reactive oxygen species (ROS) generation, and the downregulation of superoxide dismutase (SOD) activity induced by H/R treatment, while these effects were also blocked by daidzin. Furthermore, we found that Alda-1, an ALDH2 agonist, also abolished H/R-induced cytotoxicity, apoptosis, and oxidative stress, indicating that ALDH2 mediated H/R-induced H9c2 cell injury. Overall, these results suggested that baicalin prevents H/R-induced apoptosis and oxidative stress through enhancing ALDH activity and expression in H9c2 cardiomyocytes.

Meta-Analysis of Efficacy and Safety of Low-Intensity Warfarin Therapy for East Asian Patients With Nonvalvular Atrial Fibrillation.

For patients with nonvalvular atrial fibrillation (NVAF) receiving warfarin therapy, the target international normalized ratio range of 2.0 to 3.0 is recommended by Western countries. However, this treatment carries a higher risk of bleeding which suggests more researches on whether low-intensity warfarin therapy (range <2.0 to 3.0) is suitable for East Asian patients. Three databases were searched from inception to April 21, 2016. Studies that reported thromboembolic and hemorrhagic events in low- and standard-intensity warfarin groups were included. Finally, seven studies were included in the analysis. There was a significantly decreased risk of hemorrhagic events (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.43 to 0.82, p = 0.002) with no statistically increased risk of thromboembolic events (OR 1.14, 95% CI 0.80 to 1.62, p = 0.47) in the 1.5 to 2.0 group compared with that of the 2.0 to 3.0 group. Meanwhile, there was no significant difference of cardiovascular mortality (OR 1.58, 95% CI 0.89 to 2.83, p = 0.12) between the 2 groups. Further analysis showed there was no significance in thromboembolic events (OR 1.15, 95% CI 0.83 to 1.60, p = 0.40), major bleeding events (OR 0.74, 95% CI 0.50 to 1.09, p = 0.13), and cardiovascular mortality (OR 1.45, 95% CI 0.79 to 2.65, p = 0.23) between 1.5 to 2.5 and 2.0 to 3.0 groups. Although no significant difference was found in hemorrhagic events (OR 0.76, 95% CI 0.57 to 1.01, p = 0.06), there was a decreased trend in it. In conclusion, low-intensity warfarin therapy can achieve reduced hemorrhage without increasing thromboembolism for East Asian patients with NVAF receiving warfarin therapy.

Apolipoprotein A1 polymorphisms and risk of coronary artery disease: a meta-analysis.

INTRODUCTION: It has been reported that APOA1 -75G/A polymorphism might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between APOA1-75G/A polymorphism and the risk of CAD. MATERIAL AND METHODS: A systematic search of studies on the association of single nucleotide polymorphisms (SNP) with susceptibility to CAD was conducted. A total of 9 case-control studies (1864 cases and 1196 controls) on the APOA1-75G/A polymorphism were included. RESULTS: We observed no statistically significant association between APOA1 -75G/A polymorphism and risk of CAD under the dominant genetic model (AA + AG vs. GG: OR = 1.03, 95% CI: 0.65-1.66), allelic contrast (A vs. G: OR = 0.88, 95% CI: 0.58-1.32), heterozygote model (AG vs. GG: OR = 1.24, 95% CI: 0.81-1.89) or homozygote model (AA vs. GG: OR = 0.52, 95% CI: 0.26-1.05). Significant heterogeneity between individual studies appears in all five models, but a strong association under the recessive genetic model (AA vs. AG + GG: OR = 0.51, 95% CI: 0.28-0.92). In the subgroup analysis by Hardy-Weinberg equilibrium (HWE; the presence or absence of HWE in controls), significantly decreased CAD risk and no significant heterogeneity were observed among controls consistent with HWE. Overall, the APOA1 A allele is one of the protective factors of CAD. A stronger association between APOA1-75G/A polymorphisms and CAD risk was present in the studies consistent with HWE. CONCLUSIONS: The minor allele of the APOA1-75G/A polymorphism is a protective factor for CAD, especially in the studies consistent with HWE.

Long-term statin therapy could be efficacious in reducing the lipoprotein (a) levels in patients with coronary artery disease modified by some traditional risk factors.

BACKGROUND: Lipoprotein (a) [Lp (a)] is a well-established risk factor for coronary artery disease (CAD). However, up till now, treatment of patients with higher Lp (a) levels is challenging. This current study aimed to investigate the therapeutic effects of short-, medium and long-term statin use on the Lp (a) reduction and its modifying factors. METHODS: The therapeutic duration was categorized into short-term (median, 39 days), medium term (median, 219 days) and long-term (median, 677 days). The lipid profiles before therapy served as baselines. Patients at short-, medium or long-term exactly matched with those at baseline. Every patient's lipid profiles during the follow-ups were compared to his own ones at baselines. RESULTS: The current study demonstrated that long-term statin therapy significantly decreased the Lp (a) levels in CAD patients while short-term or medium term statin therapy didn't. When grouped by statin use, only long-term simvastatin use significantly decreased the Lp (a) levels while long-term atorvastatin use insignificantly decreased the Lp (a) levels. Primary hypertension (PH), DM, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) could modify the therapeutic effects of statin use on the Lp (a) levels in CAD patients. CONCLUSIONS: The long-term statin therapy could be efficacious in reducing the Lp (a) levels in CAD patients, which has been modified by some traditional risk factors. In the era of commercial unavailability of more reliable Lp (a) lowering drugs, our findings will bolster confidence in fighting higher Lp (a) abnormalities both for patients and for doctors.

Effect of ticagrelor on the serum level of hs-CRP, ESM-1 and short-term prognosis of patients with acute STEMI.

The aim of the present study was to observe and investigate the changes in the serum level of high-sensitivity C-reactive protein (hs-CRP), the endothelial cell-specific molecule-1 (ESM-1) and short-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated by ticagrelor. We enrolled 107 patients with acute STEMI who were admitted in the Department of Cardiology for the first time with occurrence of symptoms, and we successfully performed emergency operation of percutaneous coronary intervention. The patients were divided into two groups, 54 patients in the ticagrelor group (treatment group) and 53 patients in the clopidogrel group (control group), according to the administration of ticagrelor or clopidogrel in dual anti-platelet therapy. Then, we observed the changes at the time of admission, at 24 h, and 4th and 7th day after administration and investigated the correlations between them and the effect of ticagrelor on the short-term prognosis of acute STEMI patients. Significant increases of the serum levels of hs-CRP and ESM-1 were seen in patients of the two groups 24 h after administration of drugs with statistically significant differences between the groups (P<0.05), and on the 4th and 7th day we found a downward trend with statistically significant differences (P<0.05). The level of ESM-1 enhanced the increase of hs-CRP, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P<0.001). A comparison of the occurrence rates of ischemic outcome event, bleeding and overall adverse events between the two groups yielded no statistically significant difference (P>0.05). In conclusion, the present study demonstrates that ticagrelor can reduce the prevalence of inflammatory reactions rapidly and stabilize the functions of vascular endothelium to improve the stability of atherosclerosis plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome event without any obvious increase in the risk of bleeding. Thus, ticagrelor should be recommended in clinical practices for the treatment of patients with STEMI.

Lipoprotein (a) is not significantly associated with type 2 diabetes mellitus: cross-sectional study of 1604 cases and 7983 controls.

AIMS: Lipoprotein (a) (Lp(a)), a well-established risk factor for coronary artery diseases (CAD), would also be anticipated to be associated in a similar manner with risk of type 2 diabetes mellitus (T2DM) based on the common soil hypothesis of etiology of T2DM and CAD. Unfortunately, there remains considerable uncertainty regarding the association of Lp(a) with the risk of T2DM. We aimed to examine the association of Lp(a) with T2DM. METHODS: Cross-sectional study of 1604 cases and 7983 controls was performed for identifying the association of Lp(a) with T2DM, its possible interactions with risk factors and threshold effects on T2DM. The association of Lp(a) with CAD was also examined and compared within the same study. RESULTS: On a continuous scale, 10 mg/L higher Lp(a) levels were insignificantly associated with a fully adjusted OR of 1.011, 95% CI 0.961-1.063 for T2DM. On a categorical scale, the fully adjusted ORs for T2DM were 0.733 (0.526-1.022), 0.554 (0.387-0.793), 0.848 (0.612-1.176), 0.727 (0.515-1.026), 0.692 (0.488-0.981), 0.696 (0.492-0.985), 0.719 (0.509-1.016), 0.74 (0.523-1.045), 0.809 (0.571-1.146), and 0.99 (0.962-1.019) for decile 2-10 in reference to decile 1. The magnitude of association did not increase with increasing decile (P for trend test = 0.990). In contrast, higher Lp(a) levels were significantly associated with prevalent CAD on a continuous or categorical scale in a fully adjusted model. No threshold effects were observed in terms of association of Lp(a) with T2DM or with CAD in Lp(a) <50 mg/dL. CONCLUSIONS: The current study suggested that there was a lack of association of Lp(a) levels with prevalent T2DM. In contrast, Lp(a) levels were significantly associated with CAD in a dose-responding manner. Our findings provided evidence for differential approaches to higher Lp(a) levels in patients with T2DM or with CAD.