Clinical impact of complete revascularization in elderly patients with multi-vessel coronary artery disease undergoing percutaneous coronary intervention: A sub-analysis of the SHINANO registry.

BACKGROUND: Prior reports have revealed that complete revascularization (CR) by percutaneous coronary intervention (PCI) decreased ischemic events. However, little is known about the efficacy of CR using PCI in elderly patients with multi-vessel coronary artery disease (CAD). We evaluated the 1-year effectiveness of CR-PCI in elderly patients (≥75years old) with multi-vessel CAD. METHODS: The SHINANO Registry, a prospective, observational, multi-center, all-comer cohort study, has enrolled 1923 patients. From this registry, we recruited 322 elderly patients with multi-vessel CAD. The primary endpoint was major adverse cardiovascular events ([MACE]: all-cause mortality, myocardial infarction, and stroke). RESULTS: Of the 322 elderly patients with multi-vessel CAD, 165 (51.2%) received CR and 157 (48.8%) received incomplete revascularization (ICR). MACE occurred in 44 (13.7%) patients. The incidence of MACE by survival analysis was significantly lower in the CR group than in the ICR group (7.4% vs. 21.1%, p<0.001). On multivariable Cox proportional hazards analysis of age, sex, and acute coronary syndrome (ACS), ACS and CR were independent predictors of MACE (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.29-4.80; p=0.007, HR, 0.40; 95% CI, 0.20-0.77; p=0.007, respectively). In propensity score matching of age, sex, previous heart failure, previous intracranial bleeding, ACS, and body mass index, the MACE rate was significantly lower in the CR group than in the ICR group (7.2% vs. 18.4%, p=0.015). CONCLUSIONS: Even in elderly patients over 75years old with multi-vessel CAD, CR-PCI appears to suppress mid-term ischemic events.

Prediction of 1-year clinical outcomes using the SYNTAX score in patients with prior heart failure undergoing percutaneous coronary intervention: sub-analysis of the SHINANO registry.

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.

Comparison of mid-term outcomes between patients with and without atrial fibrillation undergoing coronary stenting in the second-generation drug-eluting stent era: from the SHINANO registry.

Little is known about the mid-term outcomes of patients with atrial fibrillation (AF) who undergo coronary stenting in the second-generation drug-eluting stent (DES) era. We evaluated the 1-year outcomes of AF patients undergoing percutaneous coronary intervention (PCI) with second-generation DES. This retrospective cohort analysis used integrated data from the SHINANO registry, a prospective observational multicenter cohort study, which enrolled 1923 consecutive patients undergoing PCI for any coronary artery disease. We retrospectively recruited 917 of these patients (mean age, 71.3 ± 10.0 years; male, 77 %) who received PCI with 2nd generation DES. The primary endpoint was net adverse clinical events (NACE: cardiac death, stroke, MI, stent thrombosis, and major bleeding) at 1 year. The secondary endpoints were major adverse cardiovascular events (MACE: cardiac death, stroke, and MI), stroke, MI, and major bleeding at 1 year. One-year follow-up was completed in 871 (94.9 %) patients, of whom 85 had AF. The incidence of NACE (15.4 vs. 7.3 %, P = 0.008), MACE (10.6 vs. 5.4 %, P = 0.047), and major bleeding (6.0 vs. 2.3 %, P = 0.049) were all significantly higher in AF compared to non-AF patients. On multivariate analysis, AF was an independent predictor of NACE (HR 2.32, 95 % CI 1.24-4.34, P = 0.008). In the second-generation DES era, patients with AF undergoing PCI still have a poorer prognosis, with more thrombotic and bleeding events, than those without AF. More attention should be paid to the thrombotic and bleeding risk in AF patients undergoing PCI.

Efficacy and Safety of Percutaneous Coronary Intervention for Elderly Patients in the Second-Generation Drug-Eluting Stent Era: The SHINANO Registry.

BACKGROUND: We evaluated the 1-year outcomes of percutaneous coronary intervention (PCI) for elderly patients (aged ≥ 80 years) in the second-generation drug-eluting stent (DES) era. METHODS AND RESULTS: Between August 2012 and July 2013, 1923 consecutive patients (mean age, 71 ± 11 years; ≥80 years, 23%; men, 77%) who underwent 2250 elective/urgent PCI procedures were enrolled in the Shinshu Prospective Multicenter Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention registry. The primary end point was major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, and stroke) at 1 year. The 1-year incidence of MACEs, cardiac death, and stroke was significantly higher in elderly patients than in nonelderly patients (12.4% vs 5.3%, P < .0001; 7.8% vs 2.2%, P < .0001; and 2.8% vs 1.3%, P = .033, respectively). However, no significant difference in elective PCI procedures was detected. In elderly patients, the incidence of cardiac death and target lesion revascularization was significantly lower for DES than for non-DES (2.7% vs 10.5%, P = .0001 and 4.1% vs 8.6%, P = .029, respectively). CONCLUSION: Although elderly patients had a significantly poorer prognosis than younger patients, the adverse events rate was comparable in those patients who underwent elective PCI in the second-generation DES era.

Predictive Value of Combining the Ankle-Brachial Index and SYNTAX Score for the Prediction of Outcome After Percutaneous Coronary Intervention (from the SHINANO Registry).

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.

Lean body mass index prognostic value for cardiovascular events in patients with coronary artery disease.

OBJECTIVE: Little is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship. METHODS: The SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m2; LBMI 18.3±1.8 kg/m2; FMI 5.4±2.2 kg/m2). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year. RESULTS: Over a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan-Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4-22.2 kg/m2) (p=0.002) and lower LBMI values (11.6-17.6 kg/m2) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30). CONCLUSIONS: Lower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI. CLINICAL TRIAL REGISTRATION: UMIN-ID; 000010070.

Risk stratification using the CHA2DS2-VASc score in patients with coronary heart disease undergoing percutaneous coronary intervention; sub-analysis of SHINANO registry.

BACKGROUND: CHADS2 or CHA2DS2-VASc score is used for prediction of stroke in patients with atrial fibrillation (AF). Recently, CHADS2 score is reported to have prognostic value in acute coronary syndrome without AF. However, clinical validation of CHA2DS2-VASc score for prognostic stratification in coronary heart disease (CHD) without AF remains uncertain. In this study, we evaluate whether CHA2DS2-VASc score could predict clinical outcome in CHD without known AF. METHODS: SHINANO registry was a prospective, observational, multicenter cohort study, enrolling 1923 consecutive patients with CHD from August 2012 to July 2013. Two hundred nine patients were excluded because of known AF. We calculated CHA2DS2-VASc score in the remaining 1714 patients (mean age 70 ± 11 years, 23% female) without known AF. To assess the clinical validation of CHA2DS2-VASc score, we divided patients into 3 groups according to the tertiles (score 0-2, 3-4, and ≥ 5). The primary endpoint was MACE including death, nonfatal myocardial infarction, and ischemic stroke at 1 year. RESULTS: One-year follow-up was completed in 1632 patients (95.2%). Cumulative incidence of MACE was 139 cases. In Kaplan-Meier analysis, incidence of MACE was significantly higher in patients with CHA2DS2-VASc score ≥ 5 compared to 3-4 and 0-2 (14.6% vs. 6.8% vs. 5.3%, p < 0.001). In multivariate Cox-regression analysis, CHA2DS2-VASc score was an independent predictor for MACE (hazard ratio 1.26, 95% confidence interval 1.15-1.39p < 0.001). CONCLUSIONS: This study demonstrated that CHA2DS2-VASc score could provide prognostic information in CHD without known AF.

In-hospital clinical outcomes of elderly patients (≥80 years) undergoing percutaneous coronary intervention.

BACKGROUND: The clinical outcomes of elderly patients (≥80 years old) undergoing percutaneous coronary intervention (PCI) has not been well established, despite recent advances in both devices and techniques. METHODS AND RESULTS: We recruited patients from the SHINANO Registry, a prospective, observational, multicenter, cohort study. From August 2012 to July 2013, a total of 1,923 consecutive patients with 2,250 elective/urgent PCIs (2,105 admissions) (mean age, 71±11 years; ≥80 years, 23%; men, 77%) were enrolled. The primary endpoint was procedural success. The secondary endpoints were in-hospital death and in-hospital major adverse cardiovascular events (MACE). The procedural success rate was significantly lower (83.7% vs. 89.1%, P=0.0001), and the rates of in-hospital mortality and MACE were significantly higher in elderly than in non-elderly patients (3.6% vs. 1.5%, P=0.005; 4.4% vs. 2.3%, P=0.016, respectively). For elective PCI, the rates of procedural success and in-hospital MACE were similar between groups (90.3% vs. 91.3%, P=0.65, 2.3% vs. 1.2%, P=0.2, respectively). On multivariate analysis, being elderly was not an independent predictor of procedural failure (OR, 1.15; CI, 0.81-1.61; P=0.43). CONCLUSIONS: In elderly patients, PCI is safe and feasible. The presence of comorbidities is a more important factor than age alone.

Delay in synthesis of the 3' splice site promotes trans-splicing of the preceding 5' splice site.

Premessenger RNA (pre-mRNA) splicing can occur within an individual pre-mRNA (cis-splicing) or between separate pre-mRNAs (trans-splicing). Although a number of examples of mammalian trans-splicing have been reported, the molecular mechanisms involved are poorly understood. Here, we investigate the mechanisms of Sp1 pre-mRNA trans-splicing with human cells expressing modified Sp1 transgenes. We find that the presence of a long intron or the insertion of an RNA polymerase II pause site within an intron promotes trans-splicing. We also add examples of naturally occurring trans-splicing. We propose that Sp1 trans-splicing, and other examples of mammalian trans-splicing, are a consequence of low-frequency disruption of the normal mechanisms that couple transcription and splicing.

Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes.

The aim of the present study was to investigate the association of fructose on microangiopathy in patients with diabetes. Postprandial plasma fructose concentrations and postprandial plasma glucose concentrations were simultaneously measured 3 times within a 24-hour period (2 hours after each meal) in 38 patients with type 2 diabetes that had been admitted to the hospital. The mean postprandial plasma fructose concentrations (MPPF) and the mean postprandial plasma glucose concentrations (MPPG) were calculated. Fructose was measured by gas chromatography-mass spectrometry (GCMS). Based solely on MPPF, we were able to divide the patients into three groups: the high MPPF (31.9 +/- 6.5 micromol/L) group (n = 12), the middle MPPF (21.2 +/- 1.8 micromol/L) group (n = 13), and the low MPPF (15.2 +/- 2.4 micromol/L) group (n = 13). Prevalence and degree of retinopathy and nephropathy were then evaluated in the 3 different groups. A significant correlation was observed in the prevalence of proliferative diabetic retinopathy (PDR) among the 3 MPPF groups (P =.024). The prevalence of PDR was higher in the high MPPF group (75.0%) than in the middle and low MPPF groups (23.1% and 38.5%, respectively). Although not significantly different statistically, the prevalence of all degrees of retinopathy showed a tendency to be higher in the high MPPF group (83.3%) than in the middle and low MPPF groups (46.2% and 46.2%, respectively) (P =.081). Nephropathy prevalence also showed a tendency to be higher in the high MPPF group (66.7%) than in the middle and low MPPF groups (38.5% and 30.8%, respectively), although the differences were not significant. The prevalence of clinical albuminuria was not significantly different among the 3 groups, but there was a tendency for it to be higher in the low MPPF group (30.8%) than in the high and middle MPPF groups (16.7% and 0%, respectively). No significant differences in glycemic indicators and mean duration of diabetes were observed among the 3 groups. The increased prevalence of retinopathy in the high MPPF group suggests that fructose is associated with retinopathy in patients with type 2 diabetes.

The trans-spliced variants of Sp1 mRNA in rat.

trans-Splicing is the biological reaction that generates a mature mRNA from separate strands of pre-mRNAs. Previously, we reported that the trans-splicing between the two Sp1 pre-mRNA strands produced an mRNA with the exon 3-2-3 alignment in human HepG2 cells. Here we describe the rat counterpart as well as a newly identified variant with the exon 3-3 alignment in cultured rat cells. A qualitative evaluation of such alignments in poly(A)(+) RNA-rich preparation showed that both alignments arose from trans-splicing rather than circularization of a single strand. The identification of the trans-spliced products in both rat and human raises the possibility that trans-splicing on Sp1 pre-mRNA is rather common to mammals. It was observed that the level of the trans-spliced variants varies in different rat organs.

Increased fructose concentrations in blood and urine in patients with diabetes.

OBJECTIVE: To investigate fructose metabolic changes in patients with diabetes. RESEARCH DESIGN AND METHODS: Serum and urinary fructose concentrations were determined in healthy subjects (n = 23) and in nondiabetic (n = 23) and diabetic patients (n = 26). Fructose was measured using our newly developed method, and (13)C(6)-fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry. RESULTS: Serum fructose concentrations in patients with diabetes (12.0 +/- 3.8 micromol/l) were significantly higher than those in healthy subjects (8.1 +/- 1.0 micromol/l, P < 0.001) and nondiabetic patients (7.7 +/- 1.6 micromol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 +/- 106.7 micromol/day) than in nondiabetic patients (37.7 +/- 23.0 micromol/day, P < 0.001). In patients with diabetes (n = 20), serum fructose concentrations (8.6 +/- 1.8 micromol/l, P < 0.001) and daily urinary fructose excretion (63.4 +/- 63.8 micromol/day, P < 0.01) significantly decreased by week 2 after admission. CONCLUSIONS: The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes.