Predicting long-term ischemic events using routine clinical parameters in patients with coronary artery disease: The OPT-CAD risk score.

BACKGROUND: The prognosis of patients with coronary artery disease (CAD) at hospital discharge was constantly varying, and postdischarge risk of ischemic events remain a concern. However, risk prediction tools to identify risk of ischemia for these patients has not yet been reported. AIMS: We sought to develop a scoring system for predicting long-term ischemic events in CAD patients receiving antiplatelet therapy that would be beneficial in appropriate personalized decision-making for these patients. METHODS: In this prospective Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD, NCT01735305) registry, a total of 14 032 patients with CAD receiving at least one kind of antiplatelet agent were enrolled from 107 centers across China, from January 2012 to March 2014. The risk scoring system was developed in a derivation cohort (enrolled initially 10 000 patients in the database) using a logistic regression model and was subsequently tested in a validation cohort (the last 4032 patients). Points in risk score were assigned based on the multivariable odds ratio of each factor. Ischemic events were defined as the composite of cardiac death, myocardial infarction or stroke. RESULTS: Ischemic events occurred in 342 (3.4%) patients in the derivation cohort and 160 (4.0%) patients in the validation cohort during 1-year follow-up. The OPT-CAD score, ranging from 0-257 points, consist of 10 independent risk factors, including age (0-71 points), heart rates (0-36 points), hypertension (0-20 points), prior myocardial infarction (16 points), prior stroke (16 points), renal insufficient (21 points), anemia (19 points), low ejection fraction (22 points), positive cardiac troponin (23 points) and ST-segment deviation (13 points). In predicting 1-year ischemic events, the area under receiver operating characteristics curve were 0.73 and 0.72 in derivation and validation cohort, respectively. The incidences of ischemic events in low- (0-90 points), medium- (91-150 points) and high-risk (≥151 points) patients were 1.6%, 5.5%, and 15.0%, respectively. Compared to GRACE score, OPT-CAD score had a better discrimination in predicting ischemic events and all-cause mortality (ischemic events: 0.72 vs 0.65, all-cause mortality: 0.79 vs 0.72, both P < .001). CONCLUSIONS: Among CAD patients, a risk score based on 10 baseline clinical variables performed better than the GRACE risk score in predicting long-term ischemic events. However, further research is needed to assess the value of the OPT-CAD score in guiding the management of antiplatelet therapy for patients with CAD.

Efficacy and safety of a second-generation biodegradable polymer sirolimus-eluting stent: One-year results of the CREDIT 2 trial.

AIMS: We performed a multicenter, randomized controlled trial to determine the noninferiority of a novel biodegradable polymer drug-eluting stent (BP-DES), the EXCEL 2 stent, to the first-generation BP-DES, the EXCEL stent. METHODS AND RESULTS: Patients (n = 419) scheduled to undergo percutaneous coronary intervention (PCI) were randomized to receive either the EXCEL 2 stent (n = 208) or the EXCEL stent (n = 211) from 15 Chinese centers. At 9 months, primary endpoint in-stent late loss (LL) difference was -0.03 mm (95% confidence interval: -0.09 mm to 0.04 mm) between the EXCEL 2 group (0.14 ± 0.26 mm) and the EXCEL group (0.16 ± 0.36 mm), demonstrating the noninferiority of EXCEL 2 to EXCEL in terms of in-stent LL (P for noninferiority < .0001). Besides, target lesion failure (TLF) was statistically lower in EXCEL 2 group compared with EXCEL through 1 year (HR [95%CI] = 0.45 [0.20,0.98], Plog-rank  = .04). Definite/probable ST was observed in 0.0% vs 1.9% (P = .12) of EXCEL 2 vs EXCEL-treated subjects. CONCLUSIONS: The second-generation BP-DES (EXCEL 2) was noninferior to the first-generation BP-DES (EXCEL) for the primary endpoint of in-stent LL at 9 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02057978.

Evaluation of expression levels and mechanism of complement activation.

The present study aimed to reveal the expression changes of complement system activation and complement activation product C3a receptor during acute myocardial infarction. Blood samples were collected from healthy individuals and from patients with coronary artery stenosis or acute myocardial infarction. The subjects received physical examination in hospital between January and July 2015 (n=5). Cytometric bead array was performed to measure the levels of complement system activation product anaphylatoxin C3a, C4a and C5a. Immunohistochemical investigations were performed in tissues of patients who underwent coronary artery bypass grafting between January and July 2015 to detect the expression of C3a receptor. The results of cytometric bead array showed that the content of complement activation products C3a, C4a and C5a in the plasma of patients with coronary artery stenosis and acute myocardial infarction were significantly higher than those of the control group (P<0.01). The results of immunoblotting suggested that the protein expression of C3a receptor in infarct tissues of patients with acute myocardial infarction was significantly higher than that of normal tissues adjacent to the infarcted area (P<0.05). There is complement system activation in patients with acute myocardial infarction. Additionally, the increase in the expression of complement C3a receptor in tissues of infarct area suggested that C3a-C3a receptor signaling pathway may be involved in the development of myocardial infarction.

A new algorithm for calculating optimal viewing angles in coronary angiography based on 4-D cardiac computed tomography.

BACKGROUND: Coronary stenosis is the main cause of the coronary heart disease (CHD). However, coronary arteriography (CAG), which is considered as the 'gold standard' of determining the location and severity of CHD, hardly acquires a satisfactory image for some lesions by traditional viewing angles. OBJECTIVE: We proposed a new approach to calculate the optimal viewing angles of CAG system to observe vessel segment of interest. METHODS: Firstly, the 4-D coronary arteries are segmented to obtain a dynamic vessel model. Then, a "rendering" method in computer graphics is used to calculate the optimal viewing angles of the vessel segment in the entire cardiac cycle. At last, an intersection of these angles can be regarded as the optimal ones in the whole cardiac cycle. RESULTS: Within the constraint of 2% foreshortening, the single phase data show 1% foreshortening without overlapping at the optimal angles proposed by our method, compared with 1.8% foreshortening at working angles set by clinical experts. And the multi-phase experiments also have good results. CONCLUSIONS: The new approach can provide doctors optimal viewing angles of interested vessel segment in the whole cardiac cycle.

The efficacy and safety of pharmacoinvasive therapy with prourokinase for acute ST-segment elevation myocardial infarction patients with expected long percutaneous coronary intervention-related delay.

OBJECTIVES: To elucidate the efficacy and safety of pharmacoinvasive therapy by using prourokinase (prouk) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Patients with STEMI often have long percutaneous coronary intervention (PCI)-related delays due to various reasons, which are associated with poor outcomes. METHODS: A randomized study which enrolled patients from four centers in China was conducted. Patients were randomly assigned to accept routine primary PCI or prouk-PCI. The primary end points were the angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count, and myocardial blush grade. Secondary endpoints were incidence of major adverse cardiac events (MACE, defined as death from all causes, reinfarction, revascularization, or rehospitalization due to new or worsening congestive heart failure) at 30 days and 1 year. RESULTS: One hundred and ninety-seven eligible patients were enrolled, of whom 100 were randomized to the prouk-PCI group. Significantly more patients in the prouk-PCI group than in the PCI group had an opened infarct-related artery on arrival in the catheterization laboratory (48% vs. 21%, P = 0.0002) and better TIMI frame count after PCI (33 ± 6 vs. 40 ± 10, P < 0.001). At 1-year follow-up, there was a trend that patients in the prouk-PCI group had less chances to have MACE (7.0% vs. 12.6%, P = 0.235) or be readmitted to hospital due to new or worsening congestive heart failure (1.0% vs. 4.1%, P = 0.209). CONCLUSION: A strategy of emergent PCI preceded by fibrinolysis with prouk results in a better myocardial perfusion in infarct-related artery compared with primary PCI alone in patients with STEMI and long PCI-related delay.

GDF5 and BMP2 inhibit apoptosis via activation of BMPR2 and subsequent stabilization of XIAP.

GDF5 and BMP2, members of the TGF-beta superfamily of growth factors, are known to regulate apoptosis in different cell types either positively or negatively. We wanted to investigate the effects of GDF5 and BMP2 on vascular smooth muscle cells and mouse embryonic fibroblasts and disclose the mechanism by which GDF5 and BMP2 might exert anti-apoptotic effects. The effect of GDF5 and BMP2 on proliferation and/or programmed cells death was assessed in isolated human vascular smooth muscle cells and mouse embryonic fibroblasts. We demonstrate that GDF5 and BMP2 prevent apoptosis induced by serum starvation in mouse embryonic fibroblasts but not in smooth muscle cells via the BMP receptor 2 (BMPR2), which is often mutated in hereditary cases of primary pulmonary hypertension. GDF5 and BMP2 stimulate the interaction of BMPR-2 with XIAP thereby reducing the ubiquitination of XIAP, which results in enhanced protein stability. The increased concentration of XIAP counteracts apoptosis by binding and inactivating activated caspases. We conclude that the inhibition of apoptosis in mouse embryonic fibroblasts by BMP2 and GDF5 does not depend on more complex signal transduction pathways such as smad and MAPK signaling but on direct stabilization of XIAP by BMPR2.

[A randomized, double-blind, double-dummy study comparing a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide 12.5 mg to telmisartan 80 mg in Chinese hypertensive patients who failed to respond adequately to telmisartan 80 mg].

OBJECTIVE: To evaluate the efficacy and safety of a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (TH) to telmisartan 80 mg (T) in Chinese patients who failed to respond adequately to treatment with T. METHOD: This is a multi-center, randomized, double-blind, double-dummy clinical study. A total of 699 eligible hypertensive patients entered a one-week screening phase prior to the eight-week open-label T period. At the end of eight weeks, 345 patients who failed to respond to T (DBP > or = 90 mm Hg, 1 mm Hg = 0.133 kPa) were randomized to receive either TH (175 patients) or T (170 patients) for another eight weeks. Sitting and standing BP were taken 24 hours post-dose and adverse events were documented at visit with 4 weeks interval. Laboratory, ECG and physical examination were performed at screening, at baseline and at the final visit. RESULTS: After 8 weeks treatment, (1) The mean trough reduction in sitting diastolic blood pressure (SiDBP) from baseline in TH group was greater than that in T group (10.1 mm Hg vs 7.7 mm Hg, P = 0.0017). The mean trough reduction in sitting systolic blood pressure (SiSBP) from baseline was 14.2 mm Hg in TH group and 7.4 mm Hg in T group (P < 0.0001). (2) The mean trough reduction in standing DBP and standing SBP from baseline were significantly greater in TH group (8.7 mm Hg and 12.9 mm Hg) compared those in T group (7.3 mm Hg and 7.0 mmHg, P = 0.0350, P < 0.0001). (3) The number and percentage of responders in TH group (129, 74.6%) were significantly higher than in T group (100, 59.2%, P = 0.0016). (4) The incidence of the study drug-related adverse events was similar between TH and T group (3.5% vs. 3.6%, P > 0.05). CONCLUSION: TH was more effective than T in patients not responded adequately to T in Chinese hypertensive patients.

Family history of coronary heart disease is associated with a higher incidence of nonalcoholic fatty liver disease: Central obesity the likely link.

AIM: To examine the relationship between family history of coronary heart disease (CHD), hypertension, and diabetes with risk of non-alcoholic fatty liver disease (NAFLD), and the possible interaction between these family histories and metabolic components for NAFLD. METHODS: The 202 health office workers with no evidence of excessive alcohol drinking or hepatitis B or C virus infection were enrolled in the present study performed from March to June 2004. RESULTS: NAFLD was identified in 68 subjects by abdominal ultrasound. Logistic regression analysis showed that the presence of CHD family history increased the risk of NAFLD by 2.25-fold, 95% CI 1.1-4.1 (P = 0.014), while family history of diabetes or hypertension did not increase the risk. In combination with the presence of a family history of CHD, the effect on odds ratios (ORs) was increased for several metabolic features in predicting the incidence of NAFLD, including increased waist circumference, hypertriglyceridemia, hypertension and the occurrence of the metabolic syndrome. In a logistic regression model, the CHD family history enhances the summary predictive power of baseline clinical variables for NAFLD, but when the occurrence of increased waist circumference and hypertriglyceridemia are considered, the predictive value of a family history of CHD is no longer significant. CONCLUSION: This study has shown that the CHD family history may be clinically useful and associated with the occurrence of NAFLD, and that the likely link is through central obesity and the metabolic syndrome.

Blood rheological properties are strongly related to the metabolic syndrome in middle-aged Chinese.

The current investigation sought to evaluate the relation between hemorheological properties and the metabolic syndrome. 1400 office workers aged 35 to 59 years were enrolled in this study. Waist circumference and blood pressure were determined. Plasma high-density lipoprotein (HDL cholesterol), triglyceride, fasting blood glucose, plasma insulin and whole blood viscosity (WBV) at a high-shear rate of 200 s(-1) were measured at the attendance. Metabolic syndrome was defined according to National Cholesterol Education Program (NCEP)/ATP III guidelines. The metabolic syndrome was identified in 18% of this sedentary population. Mean WBV was 4.71+/-0.56 mPa s. One-way ANOVA indicated WBV increased across subjects with 0-4 metabolic syndrome components (F=3.86, p<0.01). The highest vs. lowest quartiles of WBV occurred significantly more often among subjects as the number of metabolic syndrome components increased. Across five categories of the metabolic syndrome, the frequencies of the occurrence of the highest vs. lowest quartiles were: 0.40, 0.87, 1.31, 1.92, and 4.80, respectively, showing a significant correlation (R=0.817, p<0.05). Univariate logistic regression analysis showed that the prevalence of hyperviscosity was predicted positively by waist circumference (OR=1.018, 95% CI: 1.002-1.035, p<0.05) and negatively by HDL cholesterol (OR=0.295, 95% CI: 0.133-0.680, p<0.01), independently of age, sex, and smoking status. In summary, this study has shown that WBV is strongly related to the severity of the metabolic syndrome. We suggest that the hemorheological parameters could potentially be used as an additional indicator of the metabolic syndrome.