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Background: Soluble thrombomodulin (sTM) is a useful marker of vascular endothelial damage. Although n-3 polyunsaturated fatty acids (n-3 PUFAs) (eicosapentaenoic acid: EPA; docosahexaenoic acid: DHA) have various cardiovascular protective effects, their effect in preventing vascular endothelial damage remains unclear. Furthermore, little is known about the association of EPA and DHA with sTM using the cross-sectional study method. Methods and results: This pilot study was designed as a hospital-based cross-sectional study to investigate the relationships between serum n-3 PUFA levels and sTM level in patients with the presence of one or more risk factors for atherosclerosis. Of the 534 sequential patients who had routinely been registered to a study cohort of our institute, 324 patients without chronic kidney disease (because sTM is eliminated by renal excretion and the serum sTM level is increased by renal dysfunction) were enrolled in this study. In a multivariate analysis after adjustment for atherosclerotic risk factors, elevated EPA + DHA level was an independent variable of decreased sTM level (β = -0.183, p = 0.0006). The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001); however, multivariate analysis including EPA and DHA revealed that serum DHA (β = -0.243, p = 0.003), but not serum EPA (β = 0.049, p = 0.538), was identified as an independent negative determinant of sTM level. Conclusion: Although there are numerous unresolved issues in regard to the differences in the cardiovascular protective effects between EPA and DHA, DHA may be associated with a decrease in sTM. A large-scale trial would be warranted to demonstrate whether the beneficial effect of n3-PUFAs therapy on endothelial damage and improvement of endothelial function might also result in fewer clinical cardiovascular events. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the current status of use of inferior vena cava filters (IVCFs) in cases of pulmonary embolism at institutions belonging to the Tokyo CCU Network. Methods: We conducted a retrospective investigation of 832 consecutive cases of pulmonary embolism reported on survey forms to the Tokyo CCU Network between 2005 and 2010. Results: Of 832 cases of pulmonary embolism, IVCFs were used in 338 (40.6%) and not used in 415 (49.9%). Their use was unclear in 79 (9.5%) cases. The use rate gradually increased each year from 2005 until 2008 but decreased from 2009 onward. Moreover, 68.9% of the IVCFs used in cases were non-permanent types. In terms of pulmonary embolism severity, the rate of use was 37.2% in non-massive cases, 49.4% in sub-massive cases, 46.9% in massive cases, and 31.9% in collapse cases. Thirty-day mortality in cases of collapse in which IVCFs were not used was extremely high at 75.8%, suggesting that in many cases, rapid deterioration may occur with insufficient time for IVCF insertion. The differences in IVCF usage rate among institutions were large in the range of 12.5-90% from 2005 to 2008, which slightly declined to the range of 25.0-72.2% from 2009 to 2010. Conclusions: We elucidated the current IVCF use status in cases of pulmonary embolism at institutions belonging to the Tokyo CCU Network. Since the status of use differed among institutions, future studies of effective methods of use are required. [ABSTRACT FROM AUTHOR]

Background: Takotsubo cardiomyopathy (TC) is an acute cardiac syndrome characterized by transient left ventricular dysfunction and relatively good prognosis after discharge. However, cardiac complications during hospitalization remain to be fully determined. We attempted to determine features characterizing patients with adverse clinical outcome by comparing those with cardiac complication and without cardiac complication during hospitalization. Methods and results: We investigated 107 patients with TC from the Tokyo CCU Network database, comprising 67 cardiovascular centers in the metropolitan area during January 1 to December 31,2010. Cardiac complications were defined as cardiac death, pump failure (Killip grade ≥ II), sustained ventricular tachycardia or fibrillation (SVT/VF), and advanced atrioventricular block (AVB). Cardiac complications were observed in 41 patients (37 pump failure complicated by 3 cardiac deaths and 2 SVT/VF and 2 AVB without pump failure), and there was no cardiac complication in the remaining 66 patients. There was no difference in age, peak creatinine kinase level, C-reactive protein level and ST elevation on electrocardiogram. Multiple logistic regression analysis showed that white blood cell count (p = 0.039) and brain natriuretic peptide (p = 0.001 ) were independent predictors of in-hospital adverse cardiac complications. Conclusions: Cardiac complications are relatively high in patients with TC during hospitalization. High white blood cell count and brain natriuretic peptide level are associated with poor clinical outcome in patients with TC. [ABSTRACT FROM AUTHOR]

Background: Despite well-controlled low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia is an independent predictor of coronary events. We investigated the risk of atherosclerotic cardiovascular disease through examining the relation between triglyceride (TG) metabolism and LDL-heterogeneity as assessed by polyacrylamide-gel electrophoresis (PAGE). Methods and results: Estimated LDL-particle size [relative LDL migration (LDL-Rm value)] measured by PAGE with the LipoPhor system (Joko, Tokyo, Japan) was evaluated in 645 consecutive patients with one additional risk factor for atherosclerotic cardiovascular disease. Multivariate regression analysis after adjustments for traditional risk factors revealed an elevated triglyceride-rich lipoproteins (TRLs)-related markers [TG, remnant-like particle cholesterol (RLP-C), very LDL (VLDL) fraction, apolipoprotein (apo) C-II, and apo C-III] level to be an independent predictor of smaller-size LDL-particle size, both in the overall population, and in a subset of patients with serum LDL-C <100 mg/dL. Even among the patients with LDL-C levels <100 mg/dL, the serum levels of atherogenic lipid markers in those with a LDL-Rm value ≥0.40, suggesting the presence of large amounts of small-dense LDL and upper limit (mean + 2 standard deviation) in this population, were significantly higher than in those with a LDL-Rm value <0.40. Moreover, the serum levels of TRLs-related markers showed high accurate area under the receiveroperating characteristic curve (TG, 0.896; RLP-C, 0.875; VLDL fraction, 0.803; apo C-II, 0.778; and apo C-III, 0.804, respectively) in terms of evaluation of the indicators of LDL-Rm value ≥0.40. Conclusion: To further reduce the risk of atherosclerotic cardiovascular disease, it may be of particular importance to pay attention not only to the quantitative change in the serum LDL-C, but also TG-metabolism associated with LDL-heterogeneity. Combined evaluation of TRLs-related markers and LDL-Rm value may be useful for assessing the risk of atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-4 (DPP-4) inhibitors may affect the serum levels of plasminogen activator inhibitor-1 (PAI-1) associated with triglyceride (TG) metabolism, which is a prognostic factor for cardiovascular disease, in diabetic patients. We conducted an 8-week, prospective, randomized study in which we assigned type 2 diabetic patients who were inadequately controlled with antidiabetic therapy to the vildagliptin group (50 mg bid, n = 49) or the control group (n = 49). The primary efficacy parameter was the change in the serum level of PAI-1, and the secondary end point was the change in the serum levels of TG-rich lipoproteins. In the vildagliptin group, significant decrease of the serum PAI-1 level by 16.3% (p <0.0001) and significant decreases of the serum TG, remnant-like particle cholesterol, and apolipoprotein B levels by 12.1% (p = 0.002), 13.9% (p = 0.003), and 9.5% (p <0.0001), respectively, were observed. No such changes were observed in the control group. Multivariate regression analyses identified the absolute change from the baseline (D) of the PAI-1, but not that of the fasting blood glucose or hemoglobin A1c, as independent predictors of the ΔTG, Δ remnant-like particle cholesterol, and Δ apolipoprotein B. In conclusion, treatment of type 2 diabetes with vildagliptin might prevent the progression of atherosclerotic cardiovascular disease in diabetic patients by decreasing the serum PAI-1 levels and improving TG metabolism. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest.Design: Ad hoc data analysis of a prospective, multicenter observational study.Setting: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013.Patients: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified.Interventions: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement.Measurements and Main Results: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14-4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46-3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01-2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission.Conclusions: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level. [ABSTRACT FROM AUTHOR]

Optimal coronary reflow is the critical key issue to ameliorate clinical outcomes in patients with cardiogenic shock complicating ST-segment elevation myocardial infarction (Shock- STEMI). We investigated our hypothesis that pre-percutaneous coronary intervention (PCI) procedural coronary thrombectomy may provide clinical advantages to attempt optimal coronary reflow in patients with Shock-STEMI. Of 7,650 patients with acute myocardial infarction registered in the Tokyo CCU Network Scientific Council from January 2009 to December 2011, a total of 180 consecutive patients (144 men, 68 ± 13 years) with Shock-STEMI who showed pre-PCI procedural Thrombolysis in Myocardial Infarction flow grade 0 (absent initial coronary flow) were recruited. Achievements of post-PCI procedural Thrombolysis in Myocardial Infarction flow grade 3 (optimal coronary reflow) and also in-hospital mortality were evaluated in those in accordance with and without coronary thrombectomy. Coronary thrombectomy was performed in 128 patients with Shock-STEMI (71% of all). Overall in-hospital mortality was 41% and that in anterior Shock-STEMI with a necessity of mechanical circulatory support increased by 59% (i.e., profound shock). Coronary thrombectomy did not affect any improvements in the achievement of optimal coronary reflow (65% vs 58%, p = 0.368) and in-hospital mortality (42% vs 37%, p = 0.484) in these patients. Even when focused on 76 patients with profound shock, neither an achievement of optimal coronary reflow (56% vs 47%, p=0.518) nor in-hospital mortality (58% vs 65%, p= 0.601) were different between with and without coronary thrombectomy. Multivariate logistic analysis did not demonstrate any association of coronary thrombectomy (p = 0.798), left main Shock-STEMI (p = 0.258), and use of mechanical circulatory support (p = 0.119) except a concentration of hemoglobin (for each 1 g/dl increase, odds ratio 1.247, 95% confidence interval 1.035 to 1.531, p=0.019) with optimal coronary reflow. In conclusion, pre-PCI procedural coronary thrombectomy may have serious limitations on attempting optimal coronary reflow that indicates a necessity of promising strategies for this critical illness. [ABSTRACT FROM AUTHOR]

This study aimed to assess the balance of serum n-3 to n-6 polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS). We enrolled 1,119 patients who were treated and in whom serum PUFA level was evaluated in 5 divisions of cardiology in a metropolitan area in Japan. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with and without ACS. We also evaluated the balance of serum n-3 to n-6 PUFAs, including EPA/AA and DHA/AA ratios. EPA/AA values were 0.46 ± 0.32 and 0.50 ± 0.32 in the ACS and non-ACS groups, respectively. DHA/AA values were 0.95 ± 0.37 and 0.96 ± 0.41 in the ACS and non-ACS groups, respectively. Next, we divided the patients into 3 groups based on the tertiles of EPA/AA or tertiles of DHA/AA to determine the independent risk factors for ACS. According to multivariate logistic regression analysis, the group with the lowest EPA/ AA (£0.33) had a greater probability of ACS (odds ratio 3.14, 95% confidence interval 1.16 to 8.49), but this was not true for DHA/AA. In conclusion, an imbalance in the ratio of serum EPA to AA, but not in the ratio of DHA to AA, was significantly associated with ACS. [ABSTRACT FROM AUTHOR]