Hydroxysafflor yellow A (HSYA) targets the platelet-activating factor (PAF) receptor and inhibits human bronchial smooth muscle activation induced by PAF.

Hydroxysafflor yellow A (HSYA) is the main active ingredient of edible plant safflower. HSYA has demonstrated anti-inflammatory effects. The inflammatory response is the key mechanism responsible for asthma, and the pro-inflammatory platelet-activating factor (PAF) is known to play a role in the pathology of bronchial asthma. In this study, we stimulated human bronchial smooth muscle cells (HBSMCs) with PAF and examined the effects of HSYA on the resulting asthma-related process. PAF stimulation induced HBSMC activation, induced proliferation, increased expression of the pro-inflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α, and activated asthma-related signaling pathways. All these effects were significantly inhibited by treatment with HSYA (9, 27, 81 µmol L-1). The effects of HSYA were prevented by the addition of a PAF receptor (PAFR) antagonist or by PAFR gene silencing with small interfering RNA. These results suggest that HSYA may inhibit PAF-induced activation of HBSMCs by targeting the PAFR. Overall, these findings provide evidence that HSYA can be applied as a potential therapeutic agent in the treatment of bronchial asthma.

The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population.

BACKGROUND: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese. METHODS: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls. RESULTS: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH. CONCLUSIONS: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects.

[Clinical characteristics of 9 patients with pulmonary artery sarcoma].

OBJECTIVE: To investigate the clinical characteristics of pulmonary artery sarcoma (PAS) and to improve doctors' awareness and the early diagnosis of this disease. METHODS: The clinical data of 9 cases confirmed by operation and pathology of PAS from November 2001 to November 2012 in Beijing Anzhen Hospital were reviewed. The clinical characteristics, laboratory tests, imaging manifestation, pathology as well as follow-up were studied. Survival was determined by the Kaplan-Merier method. RESULTS: (1)Main clinical manifestations were chest distress (8/9), palpitation (2/9), syncope (2/9), cough (2/9), weight loss (2/9) and chest pain (1/9). (2)Lactate dehydrogenase (LDH) , high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) were all elevated to different extents, but D-Dimer remained in the normal range. (3) Seven cases received CTPA examination and evidenced filling defect in the main pulmonary artery trunk (6/7), left pulmonary artery (6/7), right pulmonary artery (7/7). 7 cases received TTE examination and showed enlarged right ventricle (6/7) : mean right ventricular end-diastolic diameter was (38.54 ± 16.30) mm; enlarged right atrium (7/7): mean right atrium diameter was (55.11 ± 5.45) mm; and tricuspid insufficiency (7/7) : estimated mean pulmonary artery pressure was (81.14 ± 21.17) mmHg (1 mmHg = 0.133 kPa) , and pulmonary stenosis (5/7) . Four cases received deep venous ultrasound examination and deep venous thrombosis (DVT) was found in 1 patient. Four cases received Ganz catheter examination and the preoperative and postoperative mean pulmonary artery pressure was (52.00 ± 5.23) mmHg and (23.00 ± 5.60) mmHg, respectively. (4) All 9 patients received surgery and intimal sarcoma was diagnosed in all of them. Leiomyosarcoma was diagnosed in 3 cases, leiomyo-angiosarcoma was diagnosed in 1 case, undifferentiated sarcomas was diagnosed in 1 case. (5)The 1-, 3- and 5-month survival was 71.4%, 53.6% and 35.7%, respectively, median survival time was 5 months post surgery. CONCLUSION: PAS is difficult to differentiate with PTE. PAS should be suspected in patient with right atrium, right ventricular enlargement and early appeared right heart failure, and normal D-Dimer level. Outcome for PAS patients is poor despite surgery in this cohort.

Effect of trimetazidine on recurrent angina pectoris and left ventricular structure in elderly multivessel coronary heart disease patients with diabetes mellitus after drug-eluting stent implantation: a single-centre, prospective, randomized, double-blind study at 2-year follow-up.

BACKGROUND AND OBJECTIVE: Trimetazidine has been shown to improve angina pectoris and left ventricular (LV) function in diabetic patients with ischaemic cardiomyopathy. The objective of this study was to evaluate the effects of trimetazidine on recurrent angina pectoris and LV structure after drug-eluting stent (DES) implantation in elderly multivessel coronary heart disease (CHD) patients with diabetes mellitus (DM) and a left ventricular ejection fraction (LVEF) of ≥ 50 %. METHODS: This was a single-centre, prospective, randomized, double-blind evaluation study. Between January 2010 and September 2010, 700 CHD patients with DM who were aged ≥ 65 years and undergoing coronary angiography at An Zhen Hospital (Beijing, China) were recruited and prospectively randomized to receive trimetazidine (20 mg three times daily) or placebo after DES implantation as an addition to conventional CHD treatment. The primary end points were the incidence of recurrent angina pectoris and measures of various echocardiographic parameters, which included LVEF. RESULTS: At 2-year follow-up, patients in the trimetazidine group (n = 255) showed significant improvements in the incidence (P = 0.024) and severity of angina pectoris, compared with the control group, as well as silent myocardial ischaemia (P = 0.009) and angina pectoris-free survival (P = 0.011). LV function and structure in trimetazidine-treated patients were relatively stable at 2-year follow-up, while they deteriorated in the control group (n = 255) with a significant difference between groups (all P < 0.01). The E peak to A peak (E/A) ratio in trimetazidine-treated patients and in the control group decreased after 2 years; the E/A ratio in trimetazidine-treated patients was slightly better than that in the control group, without a significant difference (P = 0.170). There was no significant difference in event-free survival for the composite end point including death, myocardial infarction, cerebrovascular accident (P = 0.422) and subsequent revascularization (P = 0.073). CONCLUSION: Adjunctive therapy with trimetazidine after DES implantation can have a beneficial effect on recurrent angina pectoris as well as LV function and structure in elderly multivessel CHD patients with DM.

Protective role of statins in patients with acute coronary syndrome aged ≥ 75 years with low LDL-C who underwent percutaneous coronary intervention.

The effect of statins in patients with acute coronary syndrome (ACS) at advanced age with lower low-density lipoprotein cholesterol (LDL-C) levels undergoing percutaneous coronary intervention (PCI) remains unknown. We evaluated the effect of statins in 220 Chinese patients with ACS aged ≥ 75 years with low LDL-C undergoing PCI. Biomarkers were measured before and 6 hours after PCI, and patients were followed up for 1 year. Biomarkers in the statin group at 6 hours post-PCI were lower than controls (creatine kinase-myocardial band 14.2 ± 5.78 vs 47.3 ± 16.4 IU/L, P = .03; cardiac troponin I 0.36 ± 0.12 vs 1.33 ± 0.47 ng/mL, P = .01; and high-sensitivity C-reactive protein 7.6 ± 4.3 vs 13.6 ± 4.5 mg/L, P = .001, respectively). Significant differences were found in major adverse cardiac events at 1 year (P = .02-.01), while target lesion revascularization alone was less at 3 months between the 2 groups (P = .03). This study demonstrates that elderly patients with ACS having low LDL-C benefit from statins regardless of type, dosage, and duration of statin administration prior to PCI.

Heart rate distribution and predictors of resting heart rate after initiation of beta-blocker treatment in patients with coronary artery disease: REsults of Sympathetic Evaluation And Research of China (RESEARCH) study.

BACKGROUND: The importance of heart rate as secondary prevention strategies for patients with coronary artery disease (CAD) is emphasized by multiple guidelines. However, limited information is available on the heart rate distribution and the change patterns of resting heart rate when initiating beta-blocker therapy among Chinese patients with CAD. METHODS: The REsults of Sympathetic Evaluation And Research of China (RESEARCH) study is a multi-centre, prospective, observational study involving 147 centers in 23 cities across China. All eligible beta-blocker naive patients were prescribed with metroprolol succinate. Initial dosage and target heart rate were selected at the discretion of their physicians in charge according to their usual institutional practice. The heart rate distribution and the change patterns of resting heart rate after initiation of beta-blocker therapy were observed. RESULTS: The majority of patients (63.6%) were prescribed with 47.5 mg metroprolol succinate. At baseline, there were only 17.4% of patients whose heart rate was less than 70 beats per minute, and the proportion reached 42.5% and 79.1%, one month and two months after initiation of beta-blockers, respectively. Multivariate linear regression analysis showed that baseline heart rate (B = 0.900, SE = 0.006, t = 141.787, P < 0.0001) and the dosage (B = -0.007, SE = 0.002, t = -3.242, P = 0.001) were independent predictors of resting heart rate 2 months after beta-blocker therapy. CONCLUSIONS: Resting heart rate is not optimally controlled in a broadly representative cohort of Chinese outpatients with CAD even after initiation of ß-blocker therapy, and baseline heart rate and the dosage of beta-blocker are both independent predictors of resting heart rate after ß-blocker therapy.

[Effects of trimetazidine therapy on left ventricular function after percutaneous coronary intervention].

OBJECTIVE: To explore the effects of trimetazidine therapy on left ventricular (LV) function after percutaneous coronary intervention (PCI). METHODS: A total of 106 patients with unstable angina pectoris underwent successful elective PCI were randomly assigned to standard therapy group (control, n = 55) or trimetazidine group (n = 51, 60 mg trimetazidine loading dose prior to PCI followed by 20 mg Tid after PCI on top of standard therapy). cTnI level was measured before and at 16-18 hours after PCI. LV function was evaluated by echocardiography and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 12 months after PCI was compared between the two groups. RESULTS: Post procedural cTnI level increased from [0.02 (0.01, 0.03)] µg/L at baseline to [0.11 (0.07, 0.13)] µg/L (P < 0.05) at 16-18 hours in the trimetazidine group, while [0.02(0.01, 0.03)] µg/L to [1.31(0.44, 2.31)] µg/L in the control group (P < 0.05). Post procedural cTnI level was significantly reduced in the trimetazidine group compared to the control group (P < 0.05). At 12 months follow-up, left ventricular ejection fraction in the trimetazidine group was significantly higher than in control group [(65.65 ± 3.94)% vs. (62.29 ± 3.06)%, P < 0.01] while incidence of MACE was similar between the two groups. CONCLUSION: Trimetazidine can reduce the post-PCI cTnI release and improve left ventricular function after PCI in patients with unstable angina pectoris.

Safety and feasibility of transradial approach for coronary bypass graft angiography and intervention.

The transradial approach (TRA) is commonly applied for coronary catheterization. However, there are few reports on the safety and feasibility of transradial catheterization in patients with prior coronary artery bypass graft (CABG) surgery. We retrospectively evaluated 124 consecutive patients who underwent graft angiography and intervention via the transradial (TRA group, n = 68) or transfemoral approach (TFA group, n = 56). The baseline clinical characteristics between the 2 groups were similar except for prior myocardial infarction. No significant difference (P > .05)was observed in procedure time, the success rate of puncture, angiography, and intervention procedure between the 2 groups. There was no significant difference in major adverse cardiac and cerebrovascular events during hospitalization. However, the vascular access site complications were significantly lower (P = .021) and the duration of hospitalization was shorter (P = .007) in the TRA group. The TRA for coronary bypass graft angiography and intervention was safe and feasible.

[Effect of previous statins on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary stenting].

OBJECTIVE: To evaluate the effect of statin pretreatment on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary intervention (PCI). METHODS: A total of 90 patients aged at 85 years old and over with coronary heart disease (CAD) undergoing stenting were enrolled. The duration of statin, hospitalization and one-year clinical follow-up outcome including all-cause mortality, major adverse cardiac event (MACE), stroke and other major hemorrhages were collected and analyzed. RESULTS: Among these patients, 33 (36.7%) received a statin pre-treatment for at least 2 days and 57 (63.3%) did not. Patients on a statin pre-treatment were more likely to have hypertension, hyperlipidemia and a history of myocardial infraction and PCI. The procedure characteristics were similar between two groups. Despite the higher risk profile, the patients on a statin pre-treatment had a lower hospitalization MACE rate (3.0% vs 10.5%, P = 0.05). However, at one year, the patients on a statin pre-treatment had a similar MACE rate (6.1% vs 3.8%, P = 0.07) as the other group. CONCLUSION: The statin pretreatment in octogenarian CAD patients with PCI may be associated with a reduced hospitalization MACE rate.

Effects of upstream tirofiban versus downstream tirofiban on myocardial damage and 180-day clinical outcomes in high-risk acute coronary syndromes patients undergoing percutaneous coronary interventions.

BACKGROUND: For patients with moderate to high-risk acute coronary syndromes (ACS) who undergo early, invasive treatment strategies, current guidelines recommend the usage of glycoprotein (GP) IIb/IIIa inhibitors as an upstream treatment for a coronary care unit or as an downstream provisional treatment for selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to evaluate the effects of upstream tirofiban versus the effects of downstream tirofiban on myocardial damage and 180-day major adverse cardiovascular events (MACE) after PCI in high-risk non-ST-segment elevation ACS (NSTE-ACS) undergoing PCI. METHODS: From July 2006 to July 2007, 160 high-risk NSTE-ACS undergoing PCI were randomized to receive upstream (within 4 - 6 hours before coronary angiography) tirofiban or downstream (the guidewire crossing the lesion) tirofiban, to evaluate the extent of myocardial damage after PCI by quantitatively and qualitatively analyzing the value of cardiac troponin I (cTnI) as well as MB isoenzyme of creatine kinase (CK-MB) before and after PCI. The incidences of 24-hour, 3-day, 7-day, 30-day and 180-day MACE after PCI were followed up and the rates of bleeding complications and thrombocytopenia during tirofiban administration were recorded. RESULTS: The peak release and cumulative release of cTnI levels within 48 hours after PCI were significantly lower with upstream tirofiban than downstream tirofiban (0.45 vs 0.63 and 0.32 vs 0.43, respectively; P < 0.05). Post-procedural cTnI elevation within 48 hours was significantly less frequent among patients who received the upstream tirofiban than those who received the downstream tirofiban (66.3% vs 87.5%, P < 0.05). The peak and cumulative release of CK-MB levels as well as post-procedural CK-MB elevation within 48 hours after PCI were not significantly different between the two groups (16 vs 14 , 5 vs 3 and 26.3% vs 36.3%, respectively; P > 0.05). The incidences of 24-hour, 3-day, and 7-day MACE after PCI were the same between the two groups (0 vs 0, 0 vs 0 and 1.25% vs 1.25%, respectively). Although the incidences of 30-day and 180-day MACE after PCI were not statistically different between the two groups, the incidences were consistently lower with upstream tirofiban (3.75% vs 6.25% and 12.99% vs 16.67%; P > 0.05). Aging (OR = 1.164, P < 0.001), hypertension (OR = 4.165, P = 0.037) and type 2 diabetes (OR = 13.628, P < 0.001) were independent risk factors of MACE. The timing of administrating the tirofiban (OR = 2.416, P = 0.153) plays an extensive role in the incidence of MACE. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during the administration of tirofiban were similar between the two groups (2.50% vs 1.25%, 1.25% vs 1.25% and 1.25% vs 1.25%, respectively; P > 0.05). CONCLUSIONS: Based on the pretreatment with aspirin and clopidogrel, upstream tirofiban was associated with attenuated minor myocardial damage and the tendency of reducing incidences of 180-day MACE after PCI among high-risk NSTE-ACS patients undergoing PCI. Aging, hypertension and type 2 diabetes were independent risk factors of MACE in high-risk NSTE-ACS patients undergoing PCI associated with tirofiban.

[Effects of upstream tirofiban versus downstream tirofiban on platelet aggregation and clinical outcomes in patients with high-risk acute coronary syndromes undergoing percutaneous coronary interventions].

OBJECTIVE: To observe the effects of upstream versus downstream application of tirofiban on platelet aggregation and clinical outcomes (major adverse cardiovascular event, MACE) in patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: From July 2006 to July 2007, 160 high-risk NSTE-ACS patients undergoing PCI were randomized to receive upstream (4-6 h prior PCI) tirofiban and downstream (immediately prior to PCI) tirofiban. Platelet aggregation inhibition was determined at admission, before coronary angiography and after PCI. Incidences of MACE at 1, 3, 7, 30 and 180 days after PCI were compared. The incidences of bleeding complications and thrombocytopenia during tirofiban treatments were recorded. RESULTS: The extent of platelet aggregation inhibition post tirofiban was significantly greater in upstream tirofiban than that in downstream tirofiban group (8% vs. 42%, P<0.05). The incidences of MACE at various time points were similar between the two groups (all P>0.05). Aging, hypertension and type-2 diabetes were independent risk factors of MACE. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during tirofiban treatments were similar between the two groups (2.5% vs. 1.3%, 1.3% vs. 1.3% and 1.3% vs. 1.3%, respectively; all P>0.05). CONCLUSION: On top of aspirin and clopidogrel, upstream application of tirofiban is associated with increased platelet aggregation inhibition but the incidences of MACE up to 180 days post tirofiban are similar in the upstream and downstream tirofiban treated patients with high-risk NSTE-ACS after PCI. Aging, hypertension and type-2 diabetes were independent risk factors of MACE in these patients.

Long-term outcome of patients of over 85 years old with acute coronary syndrome undergoing percutaneous coronary stenting: a comparison of bare metal stent and drug eluting stent.

BACKGROUND: Patients aged over 85 years have been under-represented in percutaneous coronary intervention (PCI) trials despite an increase in referrals for PCI. The long-term safety and efficacy of percutaneous coronary stenting in patients aged over 85 years with acute coronary syndrome (ACS) remain unclear. Moreover it is unknown whether there are differences between bare metal stent (BMS) and drug eluting stent (DES) in this special population. METHODS: A total of 80 patients with ACS aged over 85 years undergoing stenting (BMS group n = 21 vs DES group n = 59) were retrospectively studied. In-hospital, one year and overall clinical follow-up (12 - 36 months) of major adverse cardiac events (MACEs) including cardiac deaths, myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR) as well as stroke and other major bleeding were compared between the two groups. RESULTS: In the entire cohort, the procedure success rate was 93.8% with TIMI-3 coronary flow post-PCI in 93.8% of the vessels and the procedure related complication was 17.5%. The incidence of in-hospital MACEs in BMS group was higher (14.3% vs 6.8%, P = 0.30). The 1-year incidence of MACEs in DES group was 7.0% while there was no MACE in the BMS group. Clinical follow-up for 12 - 36 months showed that the overall survival free from MACE was 82.9% and the incidence of MACE in the BMS group was lower (5.3% vs 21.1%, P = 0.20). Multivariate regression analysis showed that the creatinine level (OR: 1.013; 95% CI: 1.006 - 1.020; P = 0.004) and hypertension (OR: 3.201; 95% CI: 1.000 - 10.663; P = 0.04) are two major factors affecting the long-term MACE. CONCLUSIONS: Percutaneous coronary stenting in patients aged over 85 years is safe and provides good short and long-term efficacy. Patients with renal dysfunction and hypertension may have a relatively high incidence of MACE.