CHA2DS2-Vasc score and CHA2DS2-Vasc-HS score are poor predictors of in-stent restenosis among patients with coronary drug-eluting stents.

OBJECTIVE: To evaluate the ability of two scoring systems (CHA2DS2-VASc score and CHA2DS2-VASc+hyperlipidaemia+smoking [CHA2DS2-VASc-HS score]) to predict in-stent restenosis (ISR) among patients undergoing drug-eluting stent (DES) implantation. METHODS: This retrospective study enrolled patients who underwent coronary angiography to assess coronary artery disease severity secondary to a diagnosis of stable angina or acute coronary syndrome that subsequently underwent DES implantations. Demographic, clinical, angiographic and biochemical parameters were compared between those patients that experienced ISR and those that did not during the study follow-up period. Univariate and multivariate logistic regression analyses were used to evaluate associations between the baseline parameters, the two scoring systems and ISR risk. RESULTS: A total of 358 patients (non-ISR group n = 316; ISR group n = 42) participated in the study. Compared with the non-ISR group, more patients in the ISR group had diabetes mellitus and received stents with smaller diameters but longer lengths. There were no significant differences with regard the predictive ability for ISR of either the CHA2DS2-Vasc or the CHA2DS2-Vasc-HS scores. Multivariate logistic regression analyses demonstrated that stent diameter, follow-up duration and glycosylated haemoglobin were independent risk factors for ISR. CONCLUSIONS: The CHA2DS2-Vasc and CHA2DS2-Vasc-HS scores did not predict ISR in patients after coronary DES placement.

The relationship between serum levels of total bilirubin and coronary plaque vulnerability.

OBJECTIVES: Previous studies have reported that serum total bilirubin provides some protection against coronary artery disease (CAD); however, the relationship between serum levels of total bilirubin and culprit/target plaque vulnerability in patients with CAD remains unclear. In this study, we investigated the association between total bilirubin and tissue characterization of coronary plaque in patients with CAD. METHODS: We enrolled 85 consecutive patients with CAD who underwent coronary angiography and intravascular ultrasound analyses [45 with acute coronary syndrome (ACS); 40 with stable angina pectoris (SAP)], and 45 age-matched participants served as the control group. Serum levels of total bilirubin in all participants were measured. The stability of the coronary plaque was compared between the ACS group and the SAP group, and the relationship between serum levels of total bilirubin and the features of coronary plaque was analyzed. RESULTS: Serum levels of total bilirubin in the ACS group were significantly lower than those in the SAP and control groups (P<0.01). Serum levels of total bilirubin were positively associated with fibrous plaques (r=0.386, P<0.001), whereas they were negatively associated with plaque burden (r=-0.413, P<0.001), lipid plaque (r=-0.419, P<0.001), and remodeling index (r=-0.275, P<0.05). Furthermore, an independent association between serum levels of total bilirubin and lipid-rich plaques (odds ratio, 0.78; 95% confidence interval, 0.64-0.95) was observed. CONCLUSION: Serum total bilirubin levels were found to be inversely associated with coronary plaque vulnerability, and decreased serum levels of total bilirubin may be an important factor for coronary lipid plaque formation, which contributes to the pathogenesis of CAD.

National prevalence of coronary heart disease and its relationship with human development index: A systematic review.

BACKGROUND: Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index. DESIGN: Systematic review. METHODS: The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value. RESULTS: Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively). CONCLUSIONS: With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors.

Myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs.

The aim of this study was to explore myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs. 24 male pigs (34.6 ± 1.3 kg) were randomly divided into three groups-control group, drug therapy group, and ECMO group. Myocardial infarction model was created in drug therapy group and ECMO group by ligating coronary artery. When cardiogenic shock occurred, drugs were given in drug therapy group and ECMO began to work in ECMO group. The pigs were killed 24 h after cardiogenic shock. Compared with in drug therapy group, left ventricular end-diastolic pressure in ECMO group decreased significantly 6 h after ligation (P < 0.05). At the end of the experiments, LV - dp/dt among three groups was significantly different, drug therapy group < ECMO group < control group. There was no difference in LV + dp/dt between drug therapy group and ECMO group. Compared with drug group, myocardial infarct size of ECMO group did not reduce significantly, but myocardial enzyme and troponin-I decreased significantly. Compared with drug therapy, ECMO improves left ventricular diastolic function, and may improve systolic function. ECMO cannot reduce myocardial infarct size without revascularization, but may have positive effects on ischemic areas by avoiding further injuring.

[Curative effects on standardized management of community patients with coronary heart disease complicated with chronic heart failure].

OBJECTIVE: To explore the effects on the standardized management of patients with coronary atherosclerotic heart disease complicated with chronic heart failure. METHODS: A total of 823 patients discharged from our department were randomly enrolled. Among 734 patients with follow-up consents, they were divided into management and control groups (n = 440, 294). The management group received standardized out-of-hospital management, regular health education and follow-ups of telephone and outpatient visits. RESULTS: Compared with the control group, the management group had lower rates of all-cause mortality, cardiac death and readmission due to cardiovascular events (CVE) declining by 26.5%, 32.2% and 57.0% respectively. Over a 4-year period, the annular survival rate of management group was 92%, 85%, 83% and 82% while that of control group 95%, 89%, 82% and 75% respectively. Patient compliance of digoxin and diuretics in the control group was inferior to that in the management group. CONCLUSION: Through standardized out-of-hospital management, the patients with coronary atherosclerotic heart disease plus chronic heart failure may achieve significant benefits through reducing the rates of all-cause mortality, cardiac death and readmission due to CVE and improving survival rate.

[Comparative analysis between cardiopulmonary exercise testing and echocardiography in patients of heart failure with normal ejection fraction].

OBJECTIVE: To assess the clinical and predictive value of cardiopulmonary exercise testing (CPET) used in heart failure with normal left ventricular ejection fraction (HFNEF). METHODS: A total of 49 HFNEF patients of (New York Heart Association) NYHA class II were randomly selected from September 2010 to July 2012. The parameters of CPET and ultrasonic cardiogram (UCG) were collected at Day 3 post-admission. Person's and partial correlations were used to perform to compare CPET and UCG. RESULTS: Pearson's correlation revealed that mitral peak velocity of early filling/early diastolic mitral annular velocity (E/E', 10.14 ± 2.05) was significantly correlated with peak oxygen uptake (VO2 peak, (24.15 ± 8.31) ml×kg⁻¹×min⁻¹, r = -0.287, P = 0.046), carbon dioxide production (VCO2, (1.63 ± 0.51) L/min, r = -0.429, P = 0.002), partial pressure of end-tidal carbon dioxide (PET CO2, (39.50 ± 7.77) mm Hg, r = -0.282, P = 0.050) and minute ventilation/carbon dioxide production (VE/VCO2, 31.69 ± 5.32, r = 0.411, P = 0.003). Early diastolic mitral annular velocity (E', (6.46 ± 1.60) cm/s) was relevant to VO2 peak (r = 0.351, P = 0.013), VCO(2) (r = 0.452, P = 0.001), PET CO2 (r = 0.310, P = 0.030), VE/VCO2 (r = -0.434, P = 0.002) and respiratory exchange ratio (RER, 1.18 ± 0.13, r = 0.350, P = 0.014). After adjustment, VCO2 was correlated with E/E' (r = -0.369, P = 0.019) and E' (r = 0.393, P = 0.010). VE/VCO2 was relevant to E/E' (r = 0.414, P = 0.006) and E' (r = -0.334, P = 0.031). CONCLUSION: For HFNFE patients, CPET has high values of assessment and prognosis.

[Management of coronary atherosclerotic heart disease through an alliance of community and hospital].

OBJECTIVE: To evaluate the effect of out-hospital normalized management of coronary heart disease (CAD) on the end point events such as mortality, readmission, etc, and on the compliance of patients through normalized management by an alliance of community and hospital. METHODS: The samples were comprised of a total of 2000 patients in 15 communities. And 1642 patients agreed to a follow-up and signed a consent form. Ten communities were chosen as the intensive management group in which community clinicians were trained and the patient management plan was proposed and carried out. The remaining 5 communities were taken as the control group in which the community clinicians were not trained and the patients received only general management. Both groups received a follow-up of 23 months. RESULTS: Compared with the control group, the intensive manage group showed a lower risk of all-cause death, cardiac death and readmission due to cardiovascular events (CVE). They declined by 36.5% (OR 0.635, 95%CI 0.478-0.854), 41.5% (OR 0.585, 95%CI 0.428-0.800) and 56.1% (OR 0.439, 95%CI 0.315-0.612) respectively. The proportion of patients with NYHA III in the intensive management and control groups increased by 3.6% and 7.7% while that of the counterparts of NYHAIV in two groups increased by 1.6% and 6.4% respectively. The cardiac function in the patients of intensive management group was significantly superior to that in control group. Patients in both groups displayed an acceptable compliance to cardiac medications except for aspirin. The proportion of aspirin in the intensive management and control groups increased by 8.4% and 8.7% respectively (P<0.05). CONCLUSION: Through normalized management provided by an alliance of community and hospital, the rates of all-cause death and readmission due to CVE decrease significantly concurrently with an improvement of cardiac function and quality of life in CAD patients.

Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction (STEMI). METHODS: Thirty-three patients (22 men; age, (68.5 +/- 6.1) years) with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF (10 microg/kg of body weight, daily) for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events. RESULTS: No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference (P > 0.05). The same change could also be found in longitudinal variation of wall motion score index of infarct segments (P > 0.05). At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations (P > 0.05). In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up (P < 0.05), but difference of the longitudinal variation between two groups was not significant (P > 0.05). When pay attention to left ventricular ejection fraction measured by angiocardiography, difference of the longitudinal variation between groups was significant (P = 0.046). Early diastolic mitral flow velocity deceleration time changed significantly at 6- month follow-up in both groups (P = 0.05). CONCLUSIONS: Mobilization of stem cells by G-CSF after reperfusion of infarct myocardium is safe and seems to offer a pragmatic strategy for recovery of myocardial global function.

Interleukin-18 levels on admission are associated with mid-term adverse clinical events in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.

The long-term prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) has been conflicting. Thus, the purpose of this study was to test whether the level of interleukin-18 measured on admission can predict long-term adverse clinical events in patients with STEMI who were undergoing percutaneous coronary intervention (PCI). We recruited 288 consecutive STEMI patients (210 men, average age [71.42 +/- 10.32] years) with onset < 6 hours who were undergoing primary PCI, and 148 age- and gender-matched control subjects. Plasma levels of IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects. The patients with STEMI were then followed prospectively over 434 days (range, 0 to 642 days) for the occurrence of composite major adverse clinical events (MACE) (cardiac mortality, recurrent myocardial infarction, or readmission due to advanced heart failure). Patients with STEMI exhibited higher levels of plasma IL-18 (P < 0.001) compared with the control subjects. Positive correlations between IL-18 and cardiac troponin-I (cTnI) (r = 0.353, P = 0.0004) and IL-18 and high-sensitivity C-reactive protein (hs-CRP) (r = 0.420, P < 0.001) were observed by Spearman's correlations analysis. Logistic regression analysis demonstrated that IL-18 >/= 450 pg/mL (OR 10.854, 95% CI 2.328 to 50.594, P < 0.0001) was a significant independent predictor of composite MACE at 60 days. Cox regression analysis demonstrated that high plasma IL-18 levels were not correlated with the occurrence of long-term composite MACE. The level of plasma IL-18 on admission may predict 60-day adverse clinical outcome, but not the long-term adverse clinical events in patients with STEMI undergoing PCI, and may be useful for mid-term risk stratification.

Association between transforming growth factor beta1 polymorphisms and left ventricle hypertrophy in essential hypertensive subjects.

Left ventricular hypertrophy (LVH) increases the risk of cardiovascular morbid events in hypertension. TGF-beta1 is involved in pathologic states such as cardiac hypertrophy and cardiac fibrosis; we thus postulate that the TGF-beta1 polymorphism is related to LVH in hypertensives. Six hundred and eighty essential hypertensive patients were recruited. Biochemical variables and clinical data were obtained and the determination of LVH was performed by echocardiography. According to the presence of LVH, all subjects were divided into the LVH+ and LVH- group. DNA was obtained, and two coding region polymorphisms of the TGF-beta1 gene (+869 Leu-->Proat codon 10 and +915 ARG-->Pro at codon 25) were analyzed by the polymerase chain reaction. The product was cleaved with the restriction endonucleases. For the polymorphisms of the +869 Leu-->Pro at codon 10, there was no marked difference in the distributions of genotypes and the allele frequencies between the LVH+ and LVH- subjects. For +915 Arg-->Pro at codon 25, a significant difference in the distributions of genotypes of TGF-beta1 was observed. The left ventricular mass index (LVMI) in Arg-Pro genotype carriers was significantly higher than those in the Arg-Arg and Pro-Pro carriers. Multivariate analysis showed that the Arg-Pro genotype was an independent risk factor for LVH (OR 3.23, 95% CI [1.48-5.63, P = 0.002]). The codon 10 genotypes did not show a significant association to LVH. Our data revealed a genetic association of TGF-beta1+915 Arg-->Pro at codon 25 polymorphism with LVH in a Chinese hypertensive population.

[Mechanism of cardioprotection induced by noninvasive limb ischemic preconditioning].

OBJECTIVE: To verify the inhibitory effect of mitochondrial calcium uniporter in remote preconditioning-induced cardioprotection. METHODS: By occlusion and reperfusion of left anterior descending artery, the rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vivo. Thus the ischemic reperfusion model was established. The rats were randomly assigned to undergo one of the following maneuvers: (1) remote preconditioning; (2) ruthenium red (an inhibitor of mitochondrial calcium uniporter); (3) spermine or SB202190 (an opener of mitochondrial calcium uniporter). Remote preconditioning was elicited by three cycles of 5 min of right femoral artery occlusion interspersed with 5 min of reperfusion. The mean arterial blood pressure, heart rate and lactate dehydrogenase released in plasma were measured during reperfusion but the infarct size was measured after reperfusion. RESULTS: In comparison with I/R group, remote preconditioning limited infarct size [(20.4 +/- 2.5)% vs (51.0 +/- 6.0)%] and lactate dehydrogenase release [(271 +/- 9) U/L vs (339 +/- 39)U/L] during reperfusion. On the contrary, spermine or SB202190 attenuated the reduction of infarct size and lactate dehydrogenase release induced by remote preconditioning. The group of spermine was [(40.8 +/- 9.2)% vs (20.4 +/- 2.5)%] and [(383 +/- 43) U/L vs (271 +/- 9) U/L] while the group of SB202190 was [(44.3 +/- 6.8)% vs (20.4 +/- 2.5)%] and [(356 +/- 26) U/L vs (271 +/- 9) U/L]. CONCLUSION: Inhibition of mitochondrial calcium uniporter opening is involved in the remote preconditioning-induced cardioprotection.

[Mitochondrial calcium uniporter participates in remote preconditioning induced cardioprotection in rat hearts subjected to ischemia and reperfusion].

AIM: To investigate whether mitochondrial calcium uniporter participates in the cardioprotection of remote preconditioning in rat hearts subjected to ischemia and reperfusion in vivo. METHODS: Rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion in vivo. Remote preconditioning was induced by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. The mean arterial blood pressure, heart rate, infarct size, and lactate dehydrogenase (LDH) activity in plasma during reperfusion were measured. RESULTS: Remote preconditioning reduced both the infarct size and LDH release during reperfusion. Ruthenium red, an inhibitor of mitochondrial calcium uniporter, also decreased both the infarct size and LDH release. Administration of spermine, an activator of mitochondrial calcium uniporter, canceled the reduction of infarct size and LDH release induced by remote preconditioning. CONCLUSION: These results indicate that remote preconditioning protects myocardium against ischemia and reperfusion injury, that effect may be related to inhibiting mitochondrial calcium uniporter opening.

[The study on inhabiting endothelial cell aging by targeted silencing of p22phox].

The aim of the study was to determine the importance and possible mechanism of NAD (P)H oxidase subunits P (superscript 22phox) involved in human umbilical endothelial cell lines ECV-304 aging by special short interference RNA (siRNA). Three siRNAs targeting p22phox were designed and synthesized in vitro, which were used to transfect ECV-304 cultured in vitro for selecting the most powerful and most suitable transfection concentration and time. The cell line ECV-304 was divided into three groups: control group, angiotensin II (Ang II) group, siRNA group, and Ang II + siRNA group. Cell aging was identified by beta-gal stain. Reactive oxygen species (ROS) and NO level in cells and medium were measured. RT-PCR and Western blot were used to analyze mRNA and protein expression of NAD(P)H oxidase subunit p22phox. Among the 3 siRNAs, siRNA-1 was the most powerful on gene silence with 50 nmol/L transfection concentration at 24 h and 36 h. The number of positive cells stained by beta-gal were increased in ECV-304 stimulated with Ang II, and p22phox mRNA and protein expression were increased in aging ECV-304 stimulated with Ang II, which had lower NO and higher ROS. Compared with Ang II group, ROS level was decreased and NO level was increased in Ang+siRNA group with decreased aging level. The result of the present study suggested that siRNA could induce NAD(P)H oxidase subunit p22phox gene silence, Ang II could induce ECV-304 aging cultured in vitro, and the possible pathway of endothelial cell aging is that Ang II upregulates p22phox expression, and then enhances the cell ROS level.

[Changes of serum hepatocyte growth factor before and after percutaneous coronary intervention in patients with unstable angina pectoris and significance there].

OBJECTIVE: To investigate the effect of unfitrate heparin (UFH) and low molecular weight heparin (LMWH) on the expression of serum hepatocyte growth factor (HGF) during percutaneous coronary intervention (PCI). METHODS: Seventy patients with chronic unstable angina pectoris were divided into 2 groups: PCI group (n = 49, with at least one main coronary artery branch with stenosis > or = 70%) and non-PCI group (n = 21, with the main coronary artery branch with stenosis < 70%). UFH was used at the beginning of coronary angiography in both groups and LMWH was used after PCI only in the PCI group. The serum level of HGF was measured before, during, and 1 and 7 days after PCI; and cardiac troponin 1 (cTnI) was measured before and 1 day after PCI in all 70 patients. RESULTS: The serum level of HGF of the PCI group increased during and immediately after PCI (12 322 +/- 3723 ng/L and 13 566 +/- 3767 ng/L respectively), both significantly higher than that before the procedure (1736 +/- 604 ng/L, both P < 0.0001), The serum level of HGF of the non-PCI group increased during and immediately after the procedure (10 928 +/- 2196 ng/L and 11 457 +/- 2298 ng/L respectively), both significantly higher than that before the procedure (967 +/- 349 ng/L, both P < 0.01). However, there were no significant differences in the HGF levels during and after the procedure between the PCI and non-PCI groups. The serum HGF returned to the normal level 24 h after the procedure in both groups. The serum GHF 7 days after the procedure of the cTnI (-) PCI group was significantly lower than that before the procedure (P < 0.01), however, the serum GHF 7 days after the procedure of the cTnI (+) PCI group remained relatively high, not significantly different from that before the procedure. CONCLUSION: There is an enhanced secretion of cardiac HGF in the patients with severe coronary artery disease. UFH promotes the release of serum HGF in the patients with chronic unstable angina pectoris undergoing PCI, which indicates some other biological effects in addition to its anticoagulant property. The delayed fall of serum HGF after PCI has relationship with minor myocardial infarction.

[C-reactive protein induced human endothelium cells apoptosis is associated with Bcl-2/Bax gene expression changes].

OBJECTIVE: In the present study, we examined the expression changes of Bcl-2/Bax in C-reactive protein (CRP) treated human endothelium cells in vitro. METHODS: The human umbilical vein endothelial cells (HUVEC) were cultured by digest method for 2 - 3 posterities and incubated with human CRP (0, 1, 5, 25 mg/L for 24 hours) and analyzed by flow cytometer for apoptosis ratio. The effects of CRP in various concentrations on Bcl-2/Bax mRNA and protein expression were examined by RT-PCR and Western Blotting. RESULTS: Apoptosis ratio increased, downregulated Bcl-2 (gene promoting cell survival) and upregulated Bax (gene promoting apoptosis) at mRNA and protein levels in proportion to increased CRP concentrations. CONCLUSION: These results demonstrate that Bcl-2/Bax could be regulated by CRP in human HUVECs and might play a causal role in CRP-induced apoptosis.

Relationship between hs-CRP, proMMP-1, TIMP-1 and coronary plaque morphology: intravascular ultrasound study.

BACKGROUND: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of the acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. Little studies have focused on this field. Therefore we investigated the relationship between hypersensitive C-reactive protein (hs-CRP), pro-matrix metalloproteinase-1 (proMMP-1), tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and coronary plaque morphology. METHODS: Intravascular ultrasound (IVUS) examination was done in 152 patients with confirmed coronary heart disease before percutaneous coronary intervention from February 2003 to July 2005. Plasma samples of arterial blood were collected prior to the procedure. The level of hs-CRP, proMMP-1 and TIMP-1 were respectively measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Unstable and ruptured plaque were found more frequently in patients with acute myocardial infarction and unstable angina. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in ruptured and unstable plaque group. Positive remolding, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in ruptured and unstable plaque group. The levels of plasma hs-CRP, proMMP-1 and TIMP-1 were higher in ruptured plaque group. hs-CRP > 8.94 mg/L was used to predict ruptured plaque with a ROC curve area of 0.76 [95% confidence interval (CI), 67.0% - 85.8%], sensitivity of 71.8%, specificity of 77.0% and accuracy of 69.2% (P < 0.01), similarly for proMMP-1 > 0.12 ng/ml with a ROC curve area of 0.69 [95% CI, 58.2% - 80.2%], sensitivity of 69.2%, specificity of 75.2% and accuracy of 66.2% (P < 0.01), and TIMP-1 > 83.45 ng/ml with a ROC curve area of 0.67 [95% CI, 56.2% - 78.3%], sensitivity of 66.7%, specificity of 61.9% and accuracy of 66.2% (P < 0.01). CONCLUSION: The plaque characteristics correlate with the clinical presentation. The elevation of hs-CRP, proMMP-1 and TIMP-1 are related to the plaque instability and rupture.

Kappa-opioid receptors mediate cardioprotection by remote preconditioning.

BACKGROUND: Remote preconditioning is known to be cardioprotective, but the exact mechanism has not been fully elucidated. The objective of the current study was to investigate the role of kappa-opioid receptors in cardioprotection by remote preconditioning and reveal possible underlying mechanisms. METHODS: Remote preconditioning was induced in anesthetized male Sprague-Dawley rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia-reperfusion was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Levels of lactate dehydrogenase, dynorphin, and met-enkephalin in plasma were measured. The opening of the mitochondrial permeability transition pore was monitored with fluorescent calcein in isolated ventricular myocytes. RESULTS: Both remote preconditioning and U-50,488H (10 mg/kg intravenous), a kappa-opioid receptor agonist, significantly decreased the infarct size and plasma lactate dehydrogenase level induced by ischemia-reperfusion, and these effects were attenuated by nor-binaltorphimine (10 mg/kg intravenous), a kappa-opioid receptor antagonist, and atractyloside (5 mg/kg intravenous), a mitochondrial permeability transition pore activator. However, administration of naltrindole (5 mg/kg), a delta-opioid receptor antagonist, had no effect on the cardioprotection by remote preconditioning. The dynorphin plasma level was increased after remote preconditioning treatment, but the met-enkephalin level did not change. In isolated ventricular myocytes loaded with calcein, U-50,488H (300 microM) decreased the mitochondrial permeability transition pore opening induced by calcium (200 microM), and this effect was attenuated by cotreatment with nor-binaltorphimine (5 microM) or atractyloside (20 microM). CONCLUSION: Activation of cardiac kappa-opioid receptors is involved in the cardioprotection induced by remote preconditioning, and the mitochondrial permeability transition pore may participate in the postreceptor pathway.