Amane Ike

Plasma pentraxin-3 levels are associated with coronary plaque vulnerability and are decreased by statin.

ObjectivePentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in patients with coronary artery disease. The purpose of this study was to investigate the association between the plasma levels of PTX3 and plaque vulnerability and the effect of the levels using statin in patients with coronary artery disease. MethodsWe determined the associations among the plasma levels of PTX3 and coronary plaque vulnerability in nonculprit coronary lesions with stenosis as assessed by integrated backscatter intravascular ultrasound (study 1). One hundred and eighteen consecutive patients with stable angina who underwent a percutaneous coronary intervention were enrolled. We also enrolled 53 patients with stable angina, and they were treated either with (n=36) or without (n=17) atorvastatin (10 mg/day) (study 2). ResultsIn study 1, although there was no association between the plasma levels of PTX3 and plaque vulnerability in all patients, the level of PTX3 was positively correlated with the percentage of lipid volume and negatively correlated with the percentage of fibrous volume in patients without statin treatment. There were no associations between high-sensitivity C-reactive protein levels and percentage of lipid volume and fibrous volume. Moreover, in study 2, statin therapy for 6–8 months significantly decreased the level of PTX3 in addition to high-sensitivity C-reactive protein. ConclusionThe plasma level of PTX3 may be a useful biomarker for predicting the tissue characteristics of coronary plaque using integrated backscatter intravascular ultrasound. Statin therapy may have a beneficial effect with regard to the reduction of PTX3 levels.

Associations between different types of hypoglycemic agents and the clinical outcome of percutaneous coronary intervention in diabetic patients—From the FU-Registry

BACKGROUND It is not clear whether it is reasonable to use particular drugs for glycemic control in preference to other hypoglycemic agents in terms of the clinical outcome of percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). METHODS AND RESULTS Among 2148 patients (2568 lesions) in the FU-Registry, DM patients who underwent PCI (n=758; 922 lesions) were investigated to clarify the effects of various drugs for glycemic control on the clinical outcome [major adverse cardiac events (MACEs): death, myocardial infarction (MI), and target lesion revascularization (TLR)] over approximately 300 days of follow-up (UMIN000005679). The MACEs(+) group (n=165) had a higher usage of insulin (p<0.001) and a lower usage of biguanides (BG, p<0.05) and dipeptidyl peptidase-IV inhibitors (p<0.05) at PCI, compared to the MACEs(-) group (n=593). A multivariate logistic regression analysis showed that low-density lipoprotein cholesterol, insulin use, atherosclerosis obliterans, and lesion reference might be significantly associated with MACEs, while BG use was negatively correlated with MACEs (p=0.04). The cumulative frequency of MACEs in the insulin-treated group was significantly higher (p<0.05) than that in the non-insulin group, and the strongest association between insulin with MACEs was seen in the hemoglobin (Hb) A1c 6.5-7.5% group. There tended to be a negative correlation between the use of insulin and MACEs, with risk ratios of <1, for the HbA1c >8.5% groups. CONCLUSIONS Among different hypoglycemic agents, treatment with insulin was associated with poor mid-term clinical outcomes in DM patients who underwent PCI, while BG use was negatively correlated with MACEs. It may be reasonable for patients with HbA1c >8.5% to avoid hyperglycemia and glucotoxicity, even through the use of insulin.

The impact of angulated lesions on angiographic late loss in patients with drug-eluting stent implantation

Angulated lesion was classified in moderate risk lesion subset in PTCA guidelines 2000, because angulated lesion has been associated with abrupt closure or myocardial injury. We compared angiographic late loss at 6-9 months in bending lesions to that in non-bending lesion. This study included 227 lesions (de nowo) who were implanted Cypher Sirolimus-eluting stent (SES). There were 52 bending lesions (22.9%) and 175 non-bending lesions (77.1%). There were no significant differences in age and complicated disease between the two groups except the higher prevalence of prior cerebral infarction in the bending lesion group. There were more eccentric lesions in the bending group than in the non-bending group (43.7% vs. 63.5%, p=0.01). Follow-up MLD (in stent) was not significantly different between the two groups (p=NS) and the angiographic restenosis rate was 23.6% in bending lesions and 17.8% in non-bending lesions (p=NS). In-stent and in-segment late loss were similar between the two groups (0.09+/-0.58 vs. 0.18+/-0.64, p=NS, 0.06+/-0.50 vs. 0.09+/-0.65, p=NS). No stent fracture was observed by angiography and IVUS in this study. Follow-up MLD (in stent) was not significantly different between the two groups (p=NS) and the angiographic restenosis rate was 23.6% in bending lesions and 17.8% in non-bending lesions (p=NS). Lesion bending is not associated with long-term angiographic late loss after DES implantation. DES may reduce clinical events in patients with bending lesion.

Characteristics of patients and types of lesions in patients with drug-eluting or bare-metal stent implantation in small coronary arteries: from the FU-Registry.

Although the use of drug-eluting stents (DES) has reduced the rate of restenosis, some problems remain regarding the usefulness of DES in small coronary arteries in addition to late thrombosis and a longer duration of dual-antiplatelet therapy. We considered 335 patients with 698 lesions who underwent DES or bare-metal stent (BMS) implantation, and randomly selected 172 DES and 124 BMS lesions that had undergone a complete data analysis and evaluation. Patients had a history of stable angina with at least 1 lesion with 50% diameter stenosis in a vessel and with a successfully minimum stent implantation (stent diameter=2.5mm). The baseline characteristics including the clinical presentation and cardiovascular risk factors were similar between the DES and BMS groups, except for the percentage of dyslipidemia (DL). Pre-procedure reference vessel diameter (RVD pre) in the DES group was significantly smaller than that in the BMS group (p<0.01), and stent length in the DES group was significantly longer (p<0.01). There was no significant difference in the cumulative incidence of major adverse cardiac events including the target lesion revascularization rate, whereas in-stent restenosis (ISR) in the DES group was significantly lower than that in the BMS group. In a multivariate analysis of ISR, diabetes mellitus, prior percutaneous coronary intervention, and DES use in clinical background were identified as independent predictors of ISR. In addition, RVD pre, stent length, and DES use in angiographical background were also identified. In conclusion, DES use is an independent predictor of ISR, although the DES group included more severely diseased small coronary arteries.

Results of provisional stenting with a Sirolimus-eluting stent for bifurcation lesion: Multicenter study in Japan

BACKGROUND Treatment of bifurcation lesion with a drug-eluting stent (DES) remains problematic. The purpose of this study was to investigate an appropriate treatment strategy for bifurcation lesion with a Sirolimus-eluting stent (SES). METHOD One-hundred-forty-one patients with 169 bifurcation lesions were treated at three centers in Japan using a Sirolimus-eluting stent. Forty-six lesions (39 patients) were treated on side branches, and provisional stenting was performed in these cases. We evaluated the angiographic results and clinical outcomes with this strategy. Patients with acute myocardial infarction were excluded. RESULT After a follow-up period of 184 +/- 65 days, there were no deaths or myocardial infarction (MI), and only one (2.0%) target lesion revascularization (TLR). The strategies used for side-branch treatment were balloon only (83.7%) and T or Modified T stent (16.3%). The final kissing balloon technique was performed on 53.4% overall. In patients with a 6-month follow-up angiogram who had 25 bifurcation lesions (including 5 LMT bifurcation Lesions, 6 LCX-OM Lesions, 13 LAD-Dx lesions, and 1 RCA lesion) that were treated with balloon only, the percent diameter stenosis (%DS) of the side branch at follow-up was similar to that after the procedure (47.2 +/- 34.4% vs. 46.4 +/- 24.1%). CONCLUSIONS In the treatment of bifurcation lesions using a SES, the results of provisional stenting for the side branch are acceptable. Percent DS of the side branch remained unchanged over time after PCI.

Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina

Little is known about the efficacy and safety of intensive lowering of low-density lipoprotein cholesterol (LDL-C) with statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. Fifty patients with stable angina were randomly divided into an atorvastatin (10 mg/day) (A) group and an atorvastatin (10 mg/day)/ezetimibe (10 mg/day) (A+E) group after stent implantation. Follow-up coronary angiography was performed at 6-9 months after stenting. The A and A+E groups showed significant reductions in LDL-C. The levels of LDL-C in the A+E group were significantly lower than those in the A group at follow-up, whereas there were no differences in major adverse cardiac events, in-stent restenosis, or in-stent % diameter stenosis (DS) between the groups. Only the A+E group showed a significant decrease in the levels of highly sensitive C-reactive protein. In a sub-analysis, %DS in the non-target vessel significantly decreased in both groups. Moreover, Δ%DS (Δ=the value at baseline minus that at follow-up) in the A+E group was more closely associated with LDL-C levels at follow-up than that in the A group. There were no significant differences in adverse effects between the A and A+E groups. In conclusion, although statin/ezetimibe therapy was effective and safe for intensive lipid-lowering in patients with stable angina after successful coronary stent implantation, improvement in clinical outcomes with the combination therapy remains unclear.

Associations between lipid profiles and MACE in hemodialysis patients with percutaneous coronary intervention: from the FU-Registry.

BACKGROUND It is well known that percutaneous coronary intervention (PCI) in hemodialysis (HD) patients is associated with higher rates of in-stent restenosis and major adverse cardiovascular events (MACE) compared to that in non-HD patients, even if the target value in cholesterol management is achieved. METHODS To evaluate the factors that are associated with MACE in HD patients, we selected 142 HD patients (164 lesions) without acute coronary syndrome (ACS) from 2148 patients (2568 lesions) who underwent PCI in our database of the FU-Registry [UMIN000005679, Fukuoka University Hospital EC/IRB:10-1-08(09-105)], and compared 52 patients (53 lesions) with MACE [MACE(+)] to 90 patients (111 lesions) without MACE [MACE(-)]. RESULTS Total cholesterol (TC: 150±30mg/dL vs 166±39mg/dL, p<0.05) and high-density lipoprotein cholesterol (HDL-C: 40.1±14.7mg/dL vs 47.8±13.5mg/dL, p<0.01) levels were significantly lower in the MACE(+) group at follow-up. No significant differences were observed in other parameters, including triglyceride, low-density lipoprotein cholesterol (LDL-C; LDL-C/HDL-C ratio, and % changes in HDL-C, non-HDL-C, LDL-C), and hemoglobin A1c (US National Glycohemoglobin Standardization Program) between before and after PCI. TC, LDL-C, and non-HDL-C at the time of PCI and TC, and HDL-C at the 9-month follow-up were negatively correlated with MACE, while body mass index (BMI) [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.68-0.95)], prior coronary artery bypass graft (CABG) (OR: 3.89; 95%CI: 1.29-12.6), and insulin use (OR: 3.17; 95%CI: 1.23-8.55) were strongly correlated with MACE in a multivariate analysis. CONCLUSION BMI, CABG, and insulin use, but not LDL-C, are independent predictors of MACE in HD patients, suggesting that the application of lipid management for non-HD patients to HD patients at the time of PCI may not necessarily be beneficial for medium-term clinical outcomes.

Lower frequency of non-target lesion intervention in post-successful percutaneous coronary intervention patients with an LDL to HDL cholesterol ratio below 1.5

coronary intervention patients with an LDL to HDL cholesterol ratio below 1.5 Yusuke Fukuda ⁎, Shin-ichiro Miura , Yoshihiro Tsuchiya , Yukiko Inoue-Sumi , Kazumitsu Kubota , Yousuke Takamiya , Takashi Kuwano , Hitomi Ohishi , Amane Ike , Ken Mori , Daizaburo Yanagi , Hiroaki Nishikawa , Kazuyuki Shirai , Keijiro Saku , Hidenori Urata b a Department of Cardiology, Fukuoka University, Fukuoka, Japan b Fukuoka University Chikushi Hospital, Fukuoka, Japan c Ohashi Cardiovascular Clinic, Fukuoka, Japan d White Cross Hospital, Fukuoka, Japan

Determination of the cut-off plasma adiponectin level associated with a lower risk of restenosis in patients with stable angina.

ObjectiveHypoadiponectinemia is an independent predictor for the progression of coronary artery disease (CAD); however, the importance of plasma adiponectin levels in the midterm clinical outcome in patients with CAD who underwent percutaneous coronary intervention (PCI) has not been fully elucidated. The purpose of this study was to investigate the association between plasma adiponectin levels and midterm clinical outcome in patients with CAD who underwent PCI. Materials and methodsA total of 112 patients (120 lesions) with stable angina who underwent PCI under intravascular ultrasound guidance, and who underwent follow-up coronary angiography about 8 months after PCI from August 2004 to December 2009 were enrolled in this study. ResultsPlasma adiponectin levels were significantly lower in the group with restenosis (n=13) than in the group without restenosis (n=107) (4.2±1.5 vs. 6.8±4.9 &mgr;g/ml, P<0.0001). A two-graph receiver operating characteristic curve analysis indicated that the cut-off point of adiponectin was 6.0 &mgr;g/ml. Although plasma adiponectin levels were independent of well-known risk factors of CAD, a multivariate logistic regression analysis indicated that the higher adiponectin group (patients with hyperadiponectinemia) was independently associated with lower risk of restenosis (odds ratio=0.21, 95% confidence interval=0.03–0.82). ConclusionHyperadiponectinemia (plasma adiponectin levels ≥6.0 &mgr;g/ml) is independently associated with a lower risk of restenosis. Thus, the plasma adiponectin level may be useful as a marker of restenosis independent of preinterventional intravascular ultrasound variables.

Is a bare-metal stent still useful for improving the outcome of percutaneous coronary intervention? From the FU-Registry

BACKGROUND Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is increasingly being used for the treatment of coronary artery diseases. However, the role and effectiveness of PCI with a bare metal stent (BMS) have not yet been established. METHODS Among the 2197 patients (2653 lesions) treated with PCI from 2003 to 2012 at three institutions in Fukuoka, 859 patients (1032 lesions) without acute coronary syndrome and in whom we were able to perform follow-up coronary angiography after stent placement and collect detailed data were selected for this study. Among the patients treated by BMS, the cut-off lesion reference for the development of in-stent restenosis (ISR) was calculated by comparing patients with and without ISR. In all patients with a lesion reference above/below the cut-off point of BMS-ISR, medium-term clinical and angiographic outcomes were compared between the BMS and DES groups. RESULTS In patients treated with a BMS, the lesion reference [odds ratio 0.68, 95% confidence interval (CI) 0.43-0.97, p=0.03] was strongly correlated with ISR, and the area under the receiver operating characteristic curve was 0.704, with moderate accuracy. Calculation of the cut-off lesion reference for BMS-ISR, using a relative cumulative frequency distribution and a sensitivity/specificity curve, showed that the cut-off lesion reference for BMS-ISR was 3.08mm, and the sensitivity/specificity was 60.4%. For the DES and BMS groups in cases with a lesion reference over 3.08mm, BMS placement did not correlate with ISR (odds ratio 0.98, 95% CI 0.85-1.12), and there was also no correlation between BMS and major adverse cardiac events. CONCLUSION In patients with a lesion reference≧3.08mm, medium-term clinical and angiographic outcomes were equivalent between the use of a DES and BMS. Thus, BMS placement is well worth considering, especially in patients with a lesion reference≧3.08mm, in whom double-antiplatelet therapy needs to be stopped at an early stage.