Clinical Impact of Ventricular Tachycardia and/or Fibrillation During the Acute Phase of Acute Myocardial Infarction on In-Hospital and 5-Year Mortality Rates in the Percutaneous Coronary Intervention Era.

BACKGROUND: The aim of this study was to investigate the prognostic impact of acute-phase ventricular tachycardia and fibrillation (VT/VF) on ST-segment elevation myocardial infarction (STEMI) patients in the percutaneous coronary intervention (PCI) era. METHODS AND RESULTS: Using the database of the Osaka Acute Coronary Insufficiency Study (OACIS), we studied 4,283 consecutive patients with STEMI who were hospitalized within 12 h of STEMI onset and underwent emergency PCI. Acute-phase VT/VF, defined as ≥3 consecutive ventricular premature complexes and/or VF within the 1st week of hospitalization, occurred in 997 (23.3%) patients. In-hospital mortality risk was significantly higher in patients with acute-phase VT/VF than inthose without (14.6% vs. 4.3%, adjusted hazard ratio (HR) 1.83, P=0.0013). Among patients discharged alive, 5-year mortality rates were comparable between patients with and without acute-phase VT/VF. Subgroup analysis showed that acute-phase VT/VF was associated with increased 5-year mortality after discharge in high-risk patients (GRACE Risk Score ≥115; adjusted HR 1.60, P=0.043), but not in intermediate- or low-risk patients. CONCLUSIONS: Even in the PCI era, acute-phase VT/VF was associated with higher in-hospital deaths of STEMI patients. However, the 5-year prognostic impact of acute-phase VT/VF was limited to high-risk patients. (Circ J 2016; 80: 1539-1547).

Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study.

OBJECTIVES: Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI. DESIGN: A prospective observational study. SETTING: Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. PARTICIPANTS: 2022 patients from the OACIS database. INTERVENTIONS: Genotyping of the 9p21 rs1333049 variant. PRIMARY OUTCOME MEASURES: ReMI event after survival discharge for 1 year. RESULTS: A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10(−4)), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups. CONCLUSIONS: Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI.

Association of lifestyle-related factors with circadian onset patterns of acute myocardial infarction: a prospective observational study in Japan.

OBJECTIVE: The onset of acute myocardial infarction (AMI) shows characteristic circadian variations involving a definite morning peak and a less-defined night-time peak. However, the factors influencing the circadian patterns of AMI onset and their influence on morning and night-time peaks have not been fully elucidated. DESIGN, SETTING AND PARTICIPANTS: An analysis of patients registered between 1998 and 2008 in the Osaka Acute Coronary Insufficiency Study, which is a prospective, multicentre observational study of patients with AMI in the Osaka region of Japan. The present study included 7755 consecutive patients with a known time of AMI onset. MAIN OUTCOMES AND MEASURES: A mixture of two von Mises distributions was used to examine whether a circadian pattern of AMI had uniform, unimodal or bimodal distribution, and the likelihood ratio test was then used to select the best circadian pattern among them. The hierarchical likelihood ratio test was used to identify factors affecting the circadian patterns of AMI onset. The Kaplan-Meier method was used to estimate survival curves of 1-year mortality according to AMI onset time. RESULTS: The overall population had a bimodal circadian pattern of AMI onset characterised by a high and sharp morning peak and a lower and less-defined night-time peak (bimodal p<0.001). Although several lifestyle-related factors had a statistically significant association with the circadian patterns of AMI onset, serum triglyceride levels had the most prominent association with the circadian patterns of AMI onset. Patients with triglyceride ≥150 mg/dL on admission had only one morning peak in the circadian pattern of AMI onset during weekdays, with no peaks detected on weekends, whereas all other subgroups had two peaks throughout the week. CONCLUSIONS: The circadian pattern of AMI onset was characterised by bimodality. Notably, several lifestyle-related factors, particularly serum triglyceride levels, had a strong relation with the circadian pattern of AMI onset. TRIAL REGISTRATION NUMBER: UMIN000004575.

Renin-angiotensin-aldosterone system polymorphisms and 5-year mortality in survivors of acute myocardial infarction: a report from the Osaka Acute Coronary Insufficiency Study.

This study sought to evaluate whether genetic variants in the renin-angiotensin-aldosterone system (RAAS) have an impact on long-term mortality after acute myocardial infarction (AMI) in the percutaneous coronary intervention (PCI) era. We investigated the impacts of individual and combinations of 4 major RAAS genetic variants, angiotensinogen (AGT) T1311C, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensin 2 type 1 receptor A1166C, and aldosterone synthase T4660C on 5-year mortality in 3149 post-AMI patients using multivariate Cox regression analysis. The predictive accuracy of all possible RAAS genetic combinations was evaluated using Cox regression analysis, and the best combination that affected prognosis was determined based on the minimal Akaike Information Criterion. There were 220 deaths during a median follow-up of 4.9 years. Independent analyses of any single RAAS variant did not show significant impacts on 5-year mortality. However, analyses in combination revealed that absence of both AGT CC genotype and ACE D allele was associated with lower 5-year mortality (log-rank P = 0.005). Patients with at least either of the AGT CC or ACE D allele had increased mortality with adjusted hazard ratios of 2.07 (95% confidence interval 1.18-3.65, P = 0.012), compared with those with neither the AGT CC nor ACE D allele. Among the 4 RAAS genetic variants examined, a combination of AGT and ACE polymorphisms was associated with 5-year mortality after AMI.

Comparison of 5-year survival after acute myocardial infarction using angiotensin-converting enzyme inhibitor versus angiotensin II receptor blocker.

Few studies have investigated whether angiotensin II receptor blocker (ARB) is a practical alternative to angiotensin-converting enzyme inhibitor (ACEI) for long-term use after acute myocardial infarction (AMI) in real-world practice in the percutaneous coronary intervention era. We compared 5-year survival benefits of ACEI and ARB in patients with AMI registered in the Osaka Acute Coronary Insufficiency Study. Study subjects were divided into 3 groups: ACEI (n = 4,425), ARB (n = 2,158), or patients without either drug (n = 2,442). A total of 661 deaths were recorded. Cox regression analysis revealed that treatment with either ACEI or ARB was associated with reduced 5-year mortality (adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58 to 0.83, p <0.001 and HR 0.79, 95% CI 0.64 to 0.98, p = 0.03, respectively). However, Kaplan-Meier estimates and Cox regression analyses based on propensity score revealed that ACEI was associated with better survival than ARB from 2 to 5 years after survival discharge (adjusted HR 0.53, 95% CI 0.38 to 0.74, p <0.001). These findings were confirmed in a propensity score-matched population. In conclusion, treatment with ACEI was associated with better 5-year survival after AMI.

Clinical impact of acute hyperglycemia on development of diabetes mellitus in non-diabetic patients with acute myocardial infarction.

BACKGROUND: Acute hyperglycemia (AH) after the onset of acute myocardial infarction (AMI) is a manifestation of transient abnormal glucose metabolism that may reflect AMI severity, and thus be a predictor of poor prognosis. However, it remains unknown whether AH may predict development of de novo diabetes mellitus (dn-DM) in non-diabetic AMI patients. METHODS AND RESULTS: Among AMI patients registered in the Osaka Acute Coronary Insufficiency Study between 1998 and 2007, we investigated hospital records of 1493 patients who had an admission glycated hemoglobin A1c (HbA1c) level of ≤6.0% and were subjected to glycometabolic profiling after survival discharge. dn-DM was defined as initiation of diabetic medication or documentation of an HbA1c level of ≥6.5% during the 5-year follow-up period. AH, defined as an admission serum glucose level of ≥200mg/dl, was observed in 133 (8.9%) patients. dn-DM development was more frequent in post-AMI patients with AH than those without [24.8% vs 12.0%, adjusted hazard ratio (HR) 1.776, p=0.021], particularly among patients with an HbA1c of <5.6% on admission. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a reduced incidence of dn-DM in patients with AH (adjusted HR 0.397, p=0.031). CONCLUSION: Admission AH was a predictor of dn-DM in non-diabetic post-AMI patients. Renin-angiotensin system inhibitors were associated with reduced incidence of dn-DM in post-AMI patients with AH.

Living alone and risk of cardiovascular events following discharge after acute myocardial infarction in Japan.

BACKGROUND: Little is known about the long-term risk of cardiovascular events after discharge among acute myocardial infarction (AMI) survivors living alone in Japan. METHODS AND RESULTS: A large-scale prospective, observational study in the Osaka region involved consecutive patients with AMI from January 2002 through December 2010. We evaluated the association between living alone and longitudinal risk of cardiovascular events following discharge after AMI. A Cox proportional-hazards model was used to assess the association between living alone and the primary composite endpoint consisting of major adverse cardiovascular events and total deaths. During the study period, 5845 patients (4415 male patients, 1430 female patients) were registered. Living alone was found to be independently associated with a higher risk of composite endpoint consisting of major adverse cardiovascular events and total deaths [adjusted hazard ratio (HR) 1.32; 95% confidence interval (CI): 1.11-1.58]. Multivariate-adjusted HRs of composite endpoint were 1.34 (95% CI: 1.08-1.68) among male patients and 1.31 (95% CI: 0.95-1.81) in the female patients. AMI survivors living alone tend to have a higher adjusted HR of composite endpoint than those not living alone irrespective of age and gender groups. CONCLUSIONS: From this large AMI registry in Osaka, AMI survivors living alone after discharge had a higher risk of cardiovascular events and total deaths than those not living alone.

Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction.

RATIONALE: Despite a recent decline of in-hospital mortality attributable to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Although various microRNAs have been proposed as diagnostic indicators for AMI, no microRNAs have been established as predictors of ischemic HF that develops after AMI. OBJECTIVE: We attempted to identify circulating microRNAs that can serve as reliable predictors of ischemic HF in post-AMI patients. METHODS AND RESULTS: Using sera collected a median of 18 days after AMI onset, we screened microRNAs in 21 patients who experienced development of HF within 1 year after AMI and in 65 matched controls without subsequent cardiovascular events after discharge. Among the 377 examined microRNAs, the serum level of only miR-192 was significantly upregulated in AMI patients with development of ischemic HF. Because miR-192 is reported to be p53-responsive, the serum levels of 2 other p53-responsive microRNAs, miR-194 and miR-34a, also were investigated. Interestingly, both microRNAs were coordinately increased with miR-192, particularly in exosomes, suggesting that these microRNAs function as circulating regulators of HF development via the p53 pathway. Furthermore, miR-194 and miR-34a expression levels were significantly correlated with left ventricular end-diastolic dimension 1 year after AMI. CONCLUSIONS: In the sera of post-AMI patients who experienced development of de-novo HF within 1 year of AMI onset, the levels of 3 p53-responsive microRNAs had been elevated by the early convalescent stage of AMI. Further investigations are warranted to confirm the usefulness of these circulating microRNAs for predicting the risk of development of ischemic HF after AMI.

Decreased mortality associated with statin treatment in patients with acute myocardial infarction and lymphotoxin-alpha C804A polymorphism.

AIMS: We previously reported the association of single nucleotide polymorphisms in the lymphotoxin alpha (LTα) gene with susceptibility to acute myocardial infarction (AMI) and increased mortality after discharge. In the present study, we investigated whether the adverse effect of LTα C804A polymorphism on mortality could be pharmacologically modified by statin treatment after AMI. METHODS AND RESULTS: We conducted a multicenter study that included 3486 post-AMI patients between 1998 and 2008. During a median follow-up period of 1775 days, 247 deaths were recorded. The mortality rate was significantly higher in LTα 804A allele carriers compared to non-804A allele carriers (7.9% vs. 5.7%, p = 0.011). The LTα 804A allele was significantly associated with increased mortality for post-AMI patients not receiving statins (hazard ratio [HR]: 1.48, 95% confidence interval [CI]: 1.03-2.12, p = 0.034), but not for those receiving statins (HR: 1.22, 95% CI: 0.70-2.10, p = 0.486). In-vitro experimental analyses demonstrated that the LTα 804A polymorphic protein, 26Asn-LTα3, induced monocyte-endothelial interaction and endoplasmic reticulum (ER) stress in cardiomyocytes more strongly than the LTα3 804C polymorphic protein 26Thr-LTα3. However, the effects of both LTα3 proteins were decreased and became comparable by the pretreatment of cells with pravastatin. CONCLUSION: LTα C804A polymorphism was associated with an increased risk of mortality for AMI patients, although this effect was masked in patients treated with statins. This finding is supported by the observed attenuation of 26Asn-LTα3-mediated monocyte-endothelial interaction and ER stress in cardiomyocytes treated with pravastatin. LTα C804A polymorphism may have potential as a novel therapeutic target for secondary prevention after AMI.

Elevated serum heart-type fatty acid-binding protein in the convalescent stage predicts long-term outcome in patients surviving acute myocardial infarction.

BACKGROUND: Little is known about the prognostic significance of elevated serum heart-type fatty acid-binding protein (H-FABP) in post-acute myocardial infarction (post-AMI) patients. METHODS AND RESULTS: A total of 1,283 post-AMI patients with available serum samples collected in the convalescent stage were studied. During a median follow-up period of 1,785 days, 176 patients (14%) had adverse events (all-cause mortality, n=81; non-fatal MI, n=44; readmission for heart failure [HF], n=51). Patients were divided into 2 groups according to a serum H-FABP level of 6.08ng/ml, which was determined to be the optimal cut-off for discriminating all-cause mortality based on the maximum value of the area under the receiver operating characteristic curve. Patients with elevated H-FABP (>6.08ng/ml, n=224) had a significantly higher incidence of death (18.3% vs. 3.8%, P<0.001) and readmission for HF (10.3% vs. 2.6%, P<0.001), but not of non-fatal MI (4.5% vs. 3.2%, P=0.187), compared to those with H-FABP <6.08ng/ml. Multivariate Cox regression analysis indicated that elevated serum H-FABP was associated with an increased risk of mortality (hazard ratio [HR], 1.91; 95% confidence interval [CI]: 1.03-3.51, P=0.039) and readmission for HF (HR, 2.49; 95% CI: 1.15-5.39, P=0.020). CONCLUSIONS: Elevated serum H-FABP during the convalescent stage of AMI predicted long-term mortality and readmission for HF after survival discharge in the post-AMI patients.

Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction.

BACKGROUND: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. METHODS AND RESULTS: We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. CONCLUSIONS: Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.

Incidence, predictors, and subsequent mortality risk of recurrent myocardial infarction in patients following discharge for acute myocardial infarction.

BACKGROUND: In the percutaneous coronary intervention (PCI) era, little evidence exists regarding the incidence, predictors and long-term mortality of recurrent myocardial infarction (Re-MI) following discharge for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 7,870 patients who survived AMI were studied with a median follow-up period of 3.9 years: 353 patients (4.5%) experienced Re-MI, with 7 of those dying within 30 days, which was classified as fatal Re-MI. The incidence of Re-MI per year was 2.65% for the first year, and 0.91-1.42% thereafter up to 5 years. Multivariate Cox regression analyses revealed that predictors of Re-MI were diabetes mellitus (hazard ratio (HR): 2.079, P<0.001), history of MI (HR: 1.767, P=0.001), and advanced age (HR: 1.021, P=0.001). These 3 predictors remained significant when angiographic and procedural parameters were incorporated into the analyses. The incidence and adjusted risk of Re-MI increased when these variables were clustered (P<0.001). The all-cause mortality rate was significantly higher in patients with Re-MI than in those without (HR: 2.206, P<0.001). CONCLUSIONS: In post-AMI patients treated in the PCI era, the incidence of Re-MI is low compared with that reported during the past 30 years. Patients' clinical factors of diabetes mellitus, history of MI, and advanced age appear to affect the occurrence of Re-MI after hospital discharge, and Re-MI still carries a risk for subsequent mortality.

Impact of beta blockade therapy on long-term mortality after ST-segment elevation acute myocardial infarction in the percutaneous coronary intervention era.

Although clinical guidelines recommend long-term ß-blocker (BB) therapy to decrease mortality after acute myocardial infarction, these recommendations are based predominantly on evidence from before the reperfusion and thrombolytic eras. To investigate the effects of BB therapy for patients with acute myocardial infarctions on mortality in the percutaneous coronary intervention era, a total of 5,628 consecutive patients who were admitted <24 hours after the onset of ST-segment elevation myocardial infarction, treated with emergent percutaneous coronary intervention, and discharged alive were studied. During a median follow-up period of 1,430 days, mortality rates did not differ between patients with and without BB therapy (5.2% vs 6.2%, p = 0.786). Multivariate analysis revealed that BB treatment was not associated with a reduced risk for mortality (hazard ratio 0.935, 95% confidence interval 0.711 to 1.230, p = 0.534). The results of propensity score matching also indicated that the mortality rates did not differ between the 2 groups. However, subgroup analyses among matched populations revealed that BB treatment was associated with a significantly lower mortality risk for high-risk patients, who were defined as those with Global Registry of Acute Coronary Events (GRACE) risk scores ≥121 (hazard ratio 0.596, 95% confidence interval 0.416 to 0.854, p = 0.005) or those administered diuretics (hazard ratio 0.602, 95% confidence interval 0.398 to 0.910, p = 0.016), but not for lower risk patients. In conclusion, BB treatment was associated with reduced long-term mortality in patients after ST-segment elevation myocardial infarction at higher risk, but not in those at lower risk. Although randomized controlled studies are warranted to confirm these results, the implementation of BB therapy for discharged patients with ST-segment elevation myocardial infarction may need to be assessed on the basis of individual mortality risk in the percutaneous coronary intervention era.

A subset of circulating microRNAs are predictive for cardiac death after discharge for acute myocardial infarction.

To investigate the prognostic impact of circulating microRNAs (miRs) in patients who survived acute myocardial infarction (AMI), we compared the circulating miR signature at the time of survival discharge among samples in the serum bank of the Osaka Acute Coronary Insufficiency Study. Using a high-throughput array consisting of 667 miRs, 11 miRs were found to be differentially expressed in the serum among patients at high-risk for cardiac death. Real-time RT-PCR confirmed that the serum levels of miR-155 and miR-380* were approximately 4- and 3-fold higher, respectively, in patients who experienced cardiac death within 1 year after discharge. Accordingly, a subset of circulating miRs might be predictive for cardiac death in post-AMI patients.

Oral treatment with nicorandil at discharge is associated with reduced mortality after acute myocardial infarction.

BACKGROUND: Previous studies showed that nicorandil can reduce coronary events in patients with coronary artery disease. However, it is unclear whether oral nicorandil treatment may reduce mortality following acute myocardial infarction (AMI). METHODS AND RESULTS: We examined the impact of oral nicorandil treatment on cardiovascular events in 1846 AMI patients who were hospitalized within 24 h after AMI onset, treated with emergency percutaneous coronary intervention (PCI), and discharged alive. Patients were divided into those with (Group N, n=535) and without (Group C, n=1311) oral nicorandil treatment at discharge. No significant differences in age, gender, body mass index, prevalence of coronary risk factors, or history of myocardial infarction existed between the two groups; however, higher incidences of multi-vessel disease, and a lower rate of successful PCI were observed in Group N. During the median follow-up of 709 (340-1088) days, all-cause mortality rate was 43% lower in Group N compared with Group C (2.4% vs. 4.2%, stratified log-rank test: p=0.0358). Multivariate Cox regression analysis revealed that nicorandil treatment was associated with all-cause death after discharge (Hazard ratio 0.495, 95% CI: 0.254-0.966, p=0.0393), but not for other cardiovascular events such as re-infarction, admission for heart failure, stroke and arrhythmia. CONCLUSIONS: The results suggest that oral administration of nicorandil is associated with reduced incidence of death in the setting of secondary prevention after AMI.

Effect of intracoronary thrombectomy on 30-day mortality in non-diabetic patients with acute hyperglycemia after acute myocardial infarction.

BACKGROUND: There is limited evidence about useful therapeutic interventions for patients with acute hyperglycemia (AH) after acute myocardial infarction (AMI). METHODS: We studied 2433 consecutive non-diabetic AMI patients who underwent percutaneous coronary intervention (PCI) within 24h after the onset. Patients were divided into two groups according to the presence or absence of AH (admission serum glucose level ≥ 11.1 mmol/l). We assessed the association between intracoronary thrombectomy and the clinical outcome in AMI patients with AH. RESULTS: Patients with AH had more risk factors than those without AH. The 30-day mortality rate of patients with AH was significantly higher than that of those without (11.7% vs 1.7%, p<0.001). Among patients with AH, the 30-day mortality rate was significantly lower for those with intracoronary thrombectomy than those without it (4.9% vs 17.2%, p=0.004). Among patients without AH, however, the 30-day mortality rate was similar between those with and without intracoronary thrombectomy (1.5% vs 1.9%, p=NS). Multivariate analysis showed that intracoronary thrombectomy was associated with an improved 30-day mortality rate for patients with AH (hazard ratio: HR 0.184, 95% CI 0.057-0.598, p=0.005). CONCLUSIONS: In AMI patients with AH, intracoronary thrombectomy prior to PCI might improve the 30-day mortality rate.

Impact of diabetes mellitus on rehospitalization for heart failure among survivors of acute myocardial infarction in the percutaneous coronary intervention era.

BACKGROUND: There is little data regarding the clinical impact of diabetes mellitus (DM) on heart failure (HF) among survivors of acute myocardial infarction (AMI) in the percutaneous coronary intervention (PCI) era. METHODS AND RESULTS: The present study group comprised 4,035 survivors who underwent PCI within 24 h of the onset of symptoms. DM was an independent predictor of rehospitalization for HF by multivariate analysis (hazard ratio (HR) 1.576, P=0.010). The risk of rehospitalization for HF was similar between patients with DM who did not have an enlarged left ventricular diastolic diameter (LVDd<51 mm) before discharge and patients without DM who showed an increase in LVDd (>or=51 mm) (HR 1.020, P=0.959). In the DM group, the hemoglobin A1c level before discharge was similar between patients with and without rehospitalization for HF (7.5+/-1.9% vs 7.4+/-1.6%, P=0.455), whereas high-sensitivity C-reactive protein (hs-CRP) was higher in patients with than without rehospitalization for HF (1.80+/-3.63 vs 0.75+/-2.03 mg/dl, P=0.001). CONCLUSIONS: DM is an independent predictor of rehospitalization for HF after AMI in the PCI era. Diabetic patients without left ventricular remodeling should be treated as a high-risk group for HF. Measurement of hs-CRP level may be useful for predicting rehospitalization because of HF in diabetic patients after AMI.

Lymphotoxin-alpha3 mediates monocyte-endothelial interaction by TNFR I/NF-kappaB signaling.

We recently reported that the single nucleotide polymorphisms of the lymphotoxin-(LT)alpha gene, a member of the tumor necrosis factor (TNF) family, are closely related to acute myocardial infarction; however, the precise mechanism of LTalpha signaling in atherogenesis remains unclear. We investigated the role of LTalpha3, a secreted homotrimer of LTalpha, in monocyte-endothelial cell adhesion using cultured human umbilical vein endothelial cells (HUVEC). We found that LTalpha3 induced cell adhesion molecules and activated NF-kappaB p50 and p65. LTalpha3 also induced phosphorylation of Akt, phosphorylation and degradation of IkappaB, nuclear translocation of p65, and increased adhesion of THP1 monocytes to HUVEC. These effects were mediated by TNF receptor (TNFR) I and attenuated by the phosphatidylinositol triphosphate-kinase (PI3K) inhibitors LY294002 and Wortmannin. Thus, LTalpha3 mediates the monocyte-endothelial interaction via the classical NF-kappaB pathway following TNFR I/PI3K activation, indicating it may play a role in the development of coronary artery disease.

Up-regulation of cell adhesion molecule genes in human endothelial cells stimulated by lymphotoxin alpha: DNA microarray analysis.

BACKGROUND: We recently reported that the A252G polymorphism of the Lymphotoxin-alpha (LTA) gene, a member of the tumor necrosis factor family, is strongly related with the onset of acute myocardial infarction; however, the roles of LTA in the development of atherosclerosis remain unclear. METHODS AND RESULTS: Changes in gene expression profile in cultured human umbilical vein (HUVEC) and coronary artery endothelial cells (HCAEC) treated with LTA were analyzed with high density oligonucleotide arrays comprised of 8,500 genes. LTA stimulation at 10 ng/mL for 2 hours profoundly induced gene expression associated with signal transduction, cell adhesion and chemoattraction, such as the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFkB), endothelial adhesion molecule 1 (E-Selectin), vascular cell adhesion molecule 1 (VCAM1), and monocyte chemotactic protein 1 (MCP1) (2.6, 55.7, 45.3 and 2.8 fold in HUVEC, and 2.6, 137.2, 64.0 and 13.0 fold in HCAEC, respectively). Quantitative real-time reverse transcriptase-polymerase chain reaction analysis confirmed that LTA increased the expressions of E-Selectin and VCAM1 in a dose-dependent manner both in HUVEC and HCAEC. CONCLUSION: LTA increased the expression of various genes involved in the process of atherosclerosis or inflammation in human endothelial cells, suggesting the roles of LTA in the development of atherosclerosis.

Structural confirmation of ostreocin-D by application of negative-ion fast-atom bombardment collision-induced dissociation tandem mass spectrometric methods.

Negative-ion fast-atom bombardment collision-induced dissociation tandem mass spectrometric (FAB-CID-MS/MS) methodology was successfully applied to verify the highly complex structure of ostreocin-D (MW 2633), a new palytoxin analog isolated from the marine dinoflagellate Ostreopsis siamensis and proposed to be 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin based on NMR data. The charge-remote fragmentations were facilitated by a negative charge introduced to a terminal amino group or to a hydroxyl group at the other terminus by a reaction with 2-sulfobenzoic acid cyclic anhydride. Product ions generated from the [M - H](-) ions provided information on the structural details of ostreocin-D. Comparisons between the spectral data for ostreocin-D and palytoxin also provided a rational basis for the assignments of product ions.