The Effect of Aggressive Wire Recanalization in Calcified Atheroma and Dilatation (ARCADIA) Technique in Eccentric Calcified Lesion of No-stenting Zone.

PURPOSE: The endovascular approach for eccentric calcified lesions of the no-stenting zone is challenging. This study aimed to investigate the effect of a novel technique for these lesions. METHODS: We performed EVT for severe and eccentric calcified lesions using the technique, which is presented previously and named aggressive wire recanalization in calcified atheroma and dilatation (ARCADIA). In brief, a guidewire is passed to the residual lumen firstly. Next, another guidewire is advanced into and cross through the calcified plaque and returned to the distal original lumen with intravascular ultrasound (IVUS) guided. The calcified plaque is dilated by using a scoring-balloon or non-compliant balloon. RESULTS: Consecutive 14 peripheral artery disease patients with isolated and eccentric calcification in a no-stenting zone were treated using ARCADIA technique between January 2018 and March 2020. In IVUS data, lumen cross-section area was significantly increased from 5.2 ± 2.0 mm2 to 18.1 ± 6.9 mm2 (p < 0.01), lumen area was expanded roundly evaluating as symmetry index from 0.45 ± 0.09 to 0.81 ± 0.12 (p < 0.01). There were no distal embolization and perforation after ARCADIA technique. One-year target lesion revascularization occurred in only 2 cases. The primary patency of 1 year was 85.7%. CONCLUSION: ARCADIA technique is safe and appropriate, and can be 1 option to treat for eccentric calcified lesions of the no-stenting zone as an optimal wire crossing method.

Differing effects of beta-blockers on long-term clinical outcomes following percutaneous coronary intervention between patients with mid-range and reduced left ventricular ejection fraction.

BACKGROUND: The aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF). METHODS: Data were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40-49%) and 201 patients with rEF (EF < 40%) were identified. They were assigned to groups according to users and non-users of beta-blockers and effects of beta-blockers were assessed between mrEF and rEF patients, separately. The primary outcome was a composite of all-cause death and non-fatal acute coronary syndrome. RESULTS: The median follow-up period was 5.5 years in mrEF patients and 4.3 years in rEF patients. Cumulative event-free survival was significantly lower in the group with beta-blockers than in the group without beta-blockers in rEF (p = 0.003), whereas no difference was observed in mrEF (p = 0.137) between those with and without beta-blockers. In the multivariate analysis, use of beta-blockers was associated with reduction in clinical outcomes in patients with rEF (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; p = 0.036), whereas no association was observed among those with mrEF (HR 0.74; 95% CI 0.49-1.10; p = 0.137). CONCLUSIONS: Our observational study showed that use of beta-blockers was not associated with long-term clinical outcomes in IHD patients with mrEF, whereas a significant association was observed in those with rEF.

Impact of Lipoprotein (a) Levels on Long-Term Outcomes in Patients With Coronary Artery Disease and Left Ventricular Systolic Dysfunction.

BACKGROUND: Serum levels of lipoprotein (a) (Lp(a)) could be a risk factor for adverse events in patients with coronary artery disease (CAD). However, the effect of Lp(a) on long-term outcomes in patients with left ventricular (LV) systolic dysfunction, possibly through the increased likelihood for development of heart failure (HF), remains to be elucidated. This study aimed to determine the prognostic impact of Lp(a) in patients with CAD and LV systolic dysfunction. Methods and Results: A total of 3,508 patients who underwent percutaneous coronary intervention were candidates. We analyzed 369 patients with LV systolic dysfunction (defined as LV ejection fraction <50%). They were assigned to groups according to a median level of Lp(a) (i.e., high Lp(a), ≥21.6 mg/dL, n=185; low Lp(a), <21.6 mg/dL, n=184). The primary outcome was a composite of all-cause death and readmission for acute coronary syndrome and/or HF. The median follow-up period was 5.1 years. Cumulative event-free survival was significantly worse for the group with high Lp(a) than for the group with low Lp(a) (P=0.005). In the multivariable analysis, a high Lp(a) level was an independent predictor of the primary outcomes (hazard ratio, 1.54; 95% confidence interval, 1.09-2.18; P=0.014). CONCLUSIONS: A high Lp(a) value could be associated with long-term adverse clinical outcomes among patients with CAD and LV systolic dysfunction.

Long-Term Predictive Value of High-Sensitivity C-Reactive Protein for Cancer Mortality in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a well known risk factor for the development of cardiovascular disease and cancer. We investigated the long-term impact of hs-CRP on cancer mortality in patients with stable coronary artery disease (CAD). Methods and Results: This study was a retrospective analysis of 2,867 consecutive patients who underwent percutaneous coronary intervention for stable CAD from 2000 to 2016. The patients were divided into 2 groups according to median hs-CRP. We then evaluated the association between baseline hs-CRP and both all-cause and cancer deaths. Median hs-CRP was 0.10 mg/dL (IQR, 0.04-0.27 mg/dL). The median follow-up period was 5.8 years (IQR, 2.3-10.0 years). There were 416 deaths (14.5%), including 149 cardiovascular deaths (5.2%) and 115 (4.0%) cancer deaths. On Kaplan-Meier analysis the higher hs-CRP group had a significantly higher incidence of both all-cause and cancer death (log-rank, P<0.001 and P=0.001, respectively). On multivariable analysis higher hs-CRP was significantly associated with higher risk of cancer death (HR, 1.74; 95% CI: 1.18-2.61, P=0.005). CONCLUSIONS: Elevated baseline hs-CRP was significantly associated with cancer mortality in patients with stable CAD. Hs-CRP measurement may be useful for the identification of subjects with an increased risk of cancer death.

Independent and Combined Effects of Serum Albumin and C-Reactive Protein on Long-Term Outcomes of Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Both inflammation and malnutrition have been reported to be closely linked to atherosclerosis, especially in patients with chronic kidney disease (CKD). The combined effects of serum albumin and C-reactive protein (CRP) on clinical outcomes after percutaneous coronary intervention (PCI) were investigated.Methods and Results:A total of 2,164 all-comer patients with coronary artery disease who underwent their first PCI and had data available for preprocedural serum albumin and hs-CRP levels between 2000 and 2011 were studied. Patients were assigned to 4 groups according to their median serum albumin and CRP levels (4.1 g/dL and 0.10 mg/dL, respectively). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction (MI), was evaluated. During a median follow-up period of 7.5 years, 331 cases of MACE (15.3%), including 270 deaths and 61 non-fatal MIs, occurred. Kaplan-Meier curves showed that the rates of MACE differed significantly among the groups (log-rank P<0.0001), even stratified by with or without CKD (both log-rank P<0.0001). After adjustment for established cardiovascular risk factors, low serum albumin with high CRP levels was associated with adverse cardiac events (hazard ratio 2.55, 95% confidence interval 1.72-3,88, P<0.0001, high albumin/low CRP group as reference). CONCLUSIONS: The presence of both low serum albumin and high CRP levels conferred a synergistic adverse effect on the risk for long-term MACE in patients undergoing PCI.

Impact of serum albumin levels on long-term outcomes in patients undergoing percutaneous coronary intervention.

Epidemiological studies have demonstrated an association between low serum albumin levels and both coronary artery disease (CAD) and mortality. However, the long-term clinical impact of low serum albumin level in patients with CAD undergoing percutaneous coronary intervention (PCI) has not yet been fully investigated. We studied 2860 all-comer patients with CAD who underwent their first PCI and had data available for pre-procedural serum albumin between 2000 and 2011. Patients were assigned to tertiles based on pre-procedural albumin levels. We evaluated the incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction. Mean albumin level was 4.0 ± 0.5 g/dL. Lower albumin levels were associated with older age, lower body mass index (BMI), and higher prevalences of female sex, ACS and chronic kidney disease (CKD). During the median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of MACE among albumin tertiles (albumin <3.8 g/dl: 44.3% vs. 3.8-4.1 g/dl: 38.0% vs. >4.1 g/dl: 22.9%; log-rank p < 0.0001). After adjusting for established cardiovascular risk factors including age, acute coronary syndrome, BMI and CKD, serum albumin levels were significantly associated with incidence of MACE (HR 1.74 per 1-g/dl decrease, 95% CI 1.34-2.26, p < 0.0001) and all-cause mortality (HR 1.74, 95% CI 1.30-2.33, p = 0.0002). Pre-PCI low serum albumin level was associated with worse long-term outcomes, independent of traditional risk factors. Assessing albumin levels may allow risk stratification in patients with CAD undergoing PCI.

Impact of gender difference on long-term outcomes of percutaneous coronary intervention for coronary artery disease in patients under statin treatment.

The incidence of adverse outcomes after percutaneous coronary intervention (PCI) is higher in women than in men. Statins reduce the likelihood of cardiovascular events arising in patients with coronary artery disease (CAD), but the impact of gender difference on long-term outcomes of PCI for CAD under statin treatment has not been established. We prospectively enrolled 3,580 consecutive patients with CAD who were treated by PCI at our institution between 2000 and 2011. Among these, 2,009 (43.9 %; male, n = 1619; female, n = 390) were under statin therapy at the time of PCI. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death and acute coronary syndrome (ACS). Age was significantly more advanced and the prevalences of hypertension and chronic kidney disease were higher among the female, than the male patients. Low-density lipoprotein cholesterol levels were significantly higher in women than in men (111.5 ± 38.9 vs. 107.5 ± 3 3.9 mg/dL, p = 0.04). During a median follow-up period of 6.3 years, MACE that occurred in 336 (16.7 %) patients included 206 (10.2 %) with all-cause death and 154 (7.7 %) with ACS. The cumulative rate of MACE tended to be higher in women than in men but the difference did not reach significance (19.7 vs. 16.0 %; p = 0.08, log-rank test). Multivariable Cox regression analysis showed that being female was not associated with MACE after adjusting for age (HR 1.22; 95 % CI 0.94-1.57; p = 0.13) and other variables (HR 1.14; 95 % CI 0.86-1.49; p = 0.35). Long-term clinical outcomes were comparable between male and female patients with coronary artery disease who were administered with statins and underwent PCI even though the baseline characteristics were worse among the females.

Temporal Trends in Clinical Outcome After Percutaneous Coronary Intervention 1984-2010　- Report From the Juntendo PCI Registry.

BACKGROUND: Since the introduction of PCI in 1977, it has evolved along with advances in the technology, improvement in operator technique and establishment of medical therapy. However, little is known of the improvement in clinical outcome following PCI. METHODS AND RESULTS: Data from the Juntendo PCI Registry during 1984-2010 were analyzed. The patients were divided into 3 groups according to date of index PCI: POBA era, January 1984-December 1997; BMS era, January 1998-July 2004; and DES era, August 2004-February 2010. The primary endpoint was a composite of MACE including all-cause mortality, non-fatal MI, non-fatal stroke and revascularization. A total of 3,831 patients were examined (POBA era, n=1,147; BMS era, n=1,180; DES era, n=1,504). Mean age was highest in the DES era. The prevalence of diabetes and hypertension was higher in the DES and BMS eras than in the POBA era. Unadjusted cumulative event-free survival rate for 2-year MACE was significantly different across the 3 eras. Adjusted relative risk reduction for 2-year MACE was 56% in the DES era and 34% in the BMS era, both compared with the POBA era. Age, ACS, and LVEF were associated with the incidence of MACE. CONCLUSIONS: Clinical outcome of PCI improved across the 26-year study period, despite the higher patient risk profile in the recent era.

Preprocedural High-Sensitivity C-Reactive Protein Predicts Long-Term Outcome of Percutaneous Coronary Intervention.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Less is known, however, about the association between hs-CRP and long-term outcome after PCI in the Japanese population.Methods and Results:We studied 3,039 all-comer patients with CAD who underwent their first PCI and had data available for preprocedural hs-CRP at Juntendo University between 2000 and 2011. Patients were assigned to tertiles based on preprocedural hs-CRP concentration. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death, acute coronary syndrome (ACS), and target vessel revascularization (TVR). Patients with higher hs-CRP had a higher prevalence of current smoking, chronic kidney disease and ACS, and a lower prevalence of statin use. During a median follow-up period of 6.5 years, ongoing divergence in MACE with hs-CRP tertile was noted on Kaplan-Meier curves (hs-CRP <0.08 mg/L, 26.4%; 0.08-0.25 mg/L, 38.2%; >0.25 mg/L, 45.6%; log-rank P<0.001). After adjustment for established cardiovascular risk factors, hs-CRP was associated with higher incidence of MACE (hazard ratio [HR], 1.10; 95% CI: 1.04-1.16, P<0.001) and higher all-cause mortality (HR, 1.14; 95% CI: 1.06-1.22, P<0.001). CONCLUSIONS: Preprocedural hs-CRP measurement is clinically useful for long-term risk assessment in Japanese patients with established CAD and undergoing PCI.

Long-term effect of ß-blocker in ST-segment elevation myocardial infarction in patients with preserved left ventricular systolic function: a propensity analysis.

The current guidelines for acute myocardial infarction (AMI) recommended that ß-blocker should be used in patients with decreased left ventricular (LV) systolic function for long-term period. However, the effect of ß-blocker in AMI patients with preserved LV systolic function is uncertain. We sought to assess the long-term effect of ß-blocker in AMI patients with preserved LV systolic function. During the follow-up period (1997-2011), total 3508 patients were performed percutaneous coronary intervention (PCI). Of these patients, 424 AMI patients with preserved LV systolic function [ejection fraction (EF) > 40 %] were analyzed. Median follow-up period was 4.7 years. Then, patients were divided into two groups (ß-blocker group 197 patients and no-ß-blocker group 227 patients). However, there are substantial differences in baseline characteristics between two groups. Therefore, we calculated propensity score to match the patients in ß-blocker and no-ß-blocker groups. After post-match patients (N = 206, 103 matched pair), ß-blocker therapy significantly reduced cardiac death compared with no-ß-blocker [hazard ratio (HR) 0.40, p = 0.04], whereas ß-blocker therapy was not associated with major adverse cardiac events (MACE) and all-cause death. ß-Blocker is an effective treatment for AMI patients who underwent PCI with preserved LV systolic function.

Comparing mortality between coronary artery bypass grafting and percutaneous coronary intervention with drug-eluting stents in elderly with diabetes and multivessel coronary disease.

Coronary artery disease is a critical issue that requires physicians to consider appropriate treatment strategies, especially for elderly people who tend to have several comorbidities, including diabetes mellitus (DM) and multivessel disease (MVD). Several studies have been conducted comparing clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in patients with DM and MVD. However, elderly people were excluded in those clinical studies. Therefore, there are no comparisons of clinical outcomes between CABG and PCI in elderly patients with DM and MVD. We compared all-cause mortality between PCI with drug-eluting stents (DES) and CABG in elderly patients with DM and MVD. A total of 483 (PCI; n = 256, CABG; n = 227) patients were analyzed. The median follow-up period was 1356 days (interquartile range of 810-1884). The all-cause mortality rate was not significantly different between CABG and PCI with DES groups. The CABG group had more patients with complex coronary lesions such as three-vessel disease or a left main trunk lesion. Older age, hemodialysis, and reduced LVEF were associated with increased long-term all-cause mortality in a multivariable Cox regression analysis. The rate of all-cause mortality was not significantly different between the PCI and CABG groups in elderly patients with DM and MVD in a single-center study.

Comparison of Clinical and Angiographic Outcomes After Bare Metal Stents and Drug-Eluting Stents Following Rotational Atherectomy.

Few studies have investigated the clinical outcomes of rotational atherectomy (RA) prior to and during the drugeluting stent (DES) era. The goal of this study was to assess the long-term outcome after RA followed by DES and bare metal stent (BMS) implantation in complex calcified coronary lesions and to compare the outcomes among various DESs.This was a single center retrospective observational study. Consecutive 406 patients who underwent elective RA followed by BMS or DES implantation at our institution from 2001 to 2011 were included. This study compared the long-term outcomes after treatment with RA among BMS and 3 different DESs (sirolimus-eluting stent, paclitaxel-eluting stent, and everolimus-eluting stent) implantation.The mean follow-up period was 4.6 years. Patients with DES were older and exhibited more vessel disease, longer lesion length, and smaller vessel size. Patients with BMS had a significantly higher rate of target lesion revascularization, restenosis, and larger late lumen loss than those with DES. Composite events including mortality, ACS, and target vessel revascularization were significantly higher in the BMS-RA group than in the DES-RA group. After adjustment, BMS remained an independent predictor of MACE and ACS plus death in patients treated with RA. However, there were no significant differences in late lumen loss, restenosis rate, and MACE among the 3 DES.The combination of DES-RA has a favorable effect in both the angiographic and clinical outcomes compared with BMS-RA. However, no significant differences in late loss and events rates were observed among the 3 DES groups.

Comparison of long-term clinical outcomes between sirolimus- and paclitaxel-eluting stents in real-world clinical practice.

Advances in percutaneous coronary intervention (PCI) have improved the outcomes of patients with coronary artery diseases. The advent of drug-eluting stents (DES) has dramatically reduced the rate of revascularization. The first-generation DES has yielded the main role of PCI to the second-generation DES; however, many patients had been implanted with the first-generation DES, sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Therefore, it is of importance to detect the long-term clinical outcomes in patients who underwent PCI with SES or PES. We analyzed data from our PCI cohort who underwent PCI with first-generation DES at Juntendo University Hospital between August 2004 and June 2010. The index procedure was analyzed when patients underwent multiple PCIs. Patients who were implanted with both SES and PES were excluded from this study. The study ended on December 31, 2011. The primary outcome was a composite of all-cause mortality and acute coronary syndrome (ACS). The secondary outcome was the rate of target lesion revascularization (TLR) and stent thrombosis. We analyzed data from 861 consecutive patients who underwent implantation of SES or PES. The median follow-up period was 1671 days (interquartile range 1081 and 2105). Kaplan-Meier curves for the primary endpoint did not significantly differ between the two groups (p = 0.8). The incidence of stent thrombosis was 1.4 and 1.8 per 1,000 person-years in the SES and PES groups, respectively (p = 0.9). The rate of TLR was significantly lower in the SES, than the PES group (12.6 and 38.3 per 1,000 person-years, p = 0.03). The rate of TLR was lower in the group treated with SES than PES, but the primary outcome comprising all-cause mortality and ACS was comparable between the two groups.

Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C <100 mg/dl. Patients were stratified into two groups according to HDL-C levels (low HDL-C group, baseline HDL-C <40 mg/dl; high HDL-C group, ≥40 mg/dl). Major adverse cardiac events (MACE) that included all-cause death, acute coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

Fusion of Ni Plating on CP-Titanium by Electron Beam Single-Track Scanning: Toward a New Approach for Fabricating TiNi Self-Healing Shape Memory Coating.

The limited wear resistance of commercially pure titanium (CP-Ti) hinders its use in abrasive and erosive environments, despite its good strength-weight ratio and corrosion resistance. This paper reports the first study proposing a novel method for wear-resistant TiNi coating through Ni plating and electron beam (EB) irradiation in an in situ synthetic approach. Single-track melting experiments were conducted using the EB to investigate the feasibility of forming a TiNi phase by fusing the Ni plate with the CP-Ti substrate. Varying beam powers were employed at a fixed scanning speed to determine the optimal conditions for TiNi phase formation. The concentration of the melt region was found to be approximate as estimated from the ratio of the Ni-plate thickness to the depth of the melt region, and the region with Ni-48.7 at.% Ti was successfully formed by EB irradiation. The study suggests that the mixing of Ti atoms and Ni atoms was facilitated by fluid flow induced by Marangoni and thermal convections. It is proposed that a more uniform TiNi layer can be achieved through multi-track melting under appropriate conditions. This research demonstrates the feasibility of utilizing EB additive manufacturing as a coating method and the potential for developing TiNi coatings with shape memory effects and pseudoelasticity.

Impact of Optimal Preparation Before Drug-Coated Balloon Dilatation for De Novo Lesion in Patients With Coronary Artery Disease.

BACKGROUND: Drug eluting stent (DES) remain several problems, including stent thrombosis, stent fracture and neoatherosclerosis. Stent-less Percutaneous coronary intervention (PCI) using a drug coated balloon (DCB) is a stent-less strategy, and several trials have supported the efficacy of DCB. However, the optimal preparation before using DCB was uncertain. The aim of this study was to investigate the optimal preparation for plaque oppression/debulking before DCB dilatation for de novo coronary artery lesion. METHODS: A total 936 patients were treated using DCB from 2014 to 2017 at our institution. Among them, we analyzed 247 patients who underwent PCI using DCB alone for de novo lesion. The primary end point of this study was target lesion failure (TLF). RESULTS: The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the optimal cutoff value of % plaque area to predict TLF. ROC curve analysis revealed plaque area ≥ 58.5% (AUC, 0.81) were associated with TLF. Eligible 188 patients were divided into 2 groups (plaque area ≥ 58.5% [n = 38] and <58.5% [n = 150]) according to IVUS data before using DCB. TLF was significantly higher in plaque area ≥ 58.5% group than in <58.5% group (P < 0.01). Multivariable analysis selected plaque area ≥ 58.5% as an independent predictor of TLF (hazard ratio 7.59, P < 0.01). CONCLUSIONS: Lesion preparation achieving plaque area < 58.5% was important in stent-less PCI using DCB.

Association of low glomerular filtration rate with the incidence of stroke in patients following complete coronary revascularization.

BACKGROUND: Low glomerular filtration rate (GFR) is associated with a worse outcome after coronary revascularization. Recently, a new specific equation to calculate the estimated GFR (eGFR) in Japanese populations has been reported, and it might be more accurate than the previously used equations. However, the relationship between a low GFR defined using the new equation for the Japanese population and the incidence of stroke following complete coronary revascularization is not yet known. METHODS AND RESULTS: Consecutive patients who underwent complete coronary revascularization (percutaneous coronary intervention and bypass surgery) between 1984 and 1992 were enrolled. Patients on dialysis were excluded. Enrolled patients were divided into 2 groups: the preserved GFR group and the low GFR group. Low GFR was defined as eGFR<60 ml·min⁻¹·1.73 m⁻². The incidence of fatal and non-fatal stroke was compared between the groups. Among the 1,809 patients that were enrolled, 321 were placed in the low GFR group. During follow up (mean, 11.4 [2.9] years), there were 127 (7.0%) stroke events. Multivariable analysis using a Cox proportional hazards regression model revealed that the incidence of stroke was significantly higher in the low GFR group than in the preserved GFR group (hazard ratio, 1.66; 95% confidence interval, 1.10-2.48; P = 0.008). CONCLUSIONS: Low GFR, defined as eGFR <60 ml·min⁻¹·1.73 m⁻², using a new specific equation for the Japanese population was associated with an increased risk of fatal and non-fatal stroke over a 10-year period after complete coronary revascularization.

Effect of pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modular (SPPARMα), in atherosclerosis model using low density lipoprotein receptor knock-out swine with balloon injury.

BACKGROUND: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that has key roles of lipid metabolism and inflammation. The PPARα may affects the initiation and progression of atherosclerosis by reducing inflammatory responses. Pemafibrate (K-877) is a novel selective PPARα modulator (SPPARMα), which was designed to possess higher PPARα potency and selectivity than existing PPARα agonists. The aim of this study is to evaluate the effect of pemafibrate on vascular response in coronary atherosclerosis model using low density lipoprotein receptor knock-out (LDLR-KO) pigs with balloon injury. METHODS AND RESULTS: Ten LDLR-KO pigs were randomly allocated to two groups [pemafibrate (n = 5) and control (n = 5)] and fed with a diet containing 2.0% cholesterol and 20% lard throughout the study. Balloon injury was created in 40 coronary segments two weeks after starting the oral administration of pemafibrate or placebo. Necropsy was conducted 8 weeks later. Coronary artery sections were reviewed to evaluate lesion progression and the mRNA expression levels for C-Jun, NFκ B, CCL2, CCR7, CD163 and MMP9 determined using real-time RT-PCR. LDL cholesterol at baseline was about 700 mg/dL. The mean ratio of macrophages to plaque area was significantly lower in pemafibrate group compared with control one (7.63±1.16 vs 14.04±4.51, P = 0.02) whereas no differences were observed in intimal area between groups. The mRNA levels of C-Jun, NFκB and MMP9 were significantly decreased in pemafibrate group. CONCLUSIONS: Pemafibrate was associated with inhibition of inflammatory responses in coronary artery atherosclerosis model using LDLR-KO swine with balloon injury.

Clinical impact of high-sensitivity C-reactive protein during follow-up on long-term adverse clinical outcomes in patients with coronary artery disease treated with percutaneous coronary intervention.

INTRODUCTION: C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention. METHODS: We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6-8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS). RESULTS: Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p=0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43-3.27, p=0.0002. CONCLUSION: Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI.

Impact of body mass index on long-term outcomes in Japanese patients following percutaneous coronary intervention: The Juntendo PCI Registry.

BACKGROUND: The prognostic long-term impact of body mass index (BMI) on East Asian patients with coronary artery disease remains unclear. METHODS: An observational retrospective cohort study was carried out involving 3571 patients who had undergone percutaneous coronary intervention (PCI) from 2000 to 2013. Patients were divided into the following five groups according to baseline BMI: Group 1 (underweight 1, BMI ≤20.0kg/m2); Group 2 (underweight 2, BMI=20.1-22.5kg/m2); Group 3 (normal weight, BMI=22.6-25.0kg/m2); Group 4 (overweight 1, BMI=25.1-27.5kg/m2); and Group 5 (overweight 2, BMI ≥27.6kg/m2). We then evaluated the association between BMI and both all-cause and cardiac death after PCI. RESULTS: The ratio of patients in the five groups was as follows: Group 1, 9.2%; Group 2, 21.6%; Group 3, 34.1%; Group 4, 21.1%; and Group 5, 14.5%. A decrease in age was observed from underweight to overweight, as was an increased prevalence of hypertension, diabetes mellitus, dyslipidemia, and smoking. The median follow-up period was 6.3 years (interquartile range, 3.2-9.6 years). In total, 473 deaths (frequency, 13.2%) were identified, including 183 (5.1%) cardiac deaths during follow-up. In unadjusted Cox proportional hazard analysis, using normal weight as the reference, underweight, but not overweight, was associated with a greater risk of both all-cause and cardiac death. In an adjusted model, Group 1 had the highest risk for all-cause death (hazard ratio, 1.58; 95% confidence interval, 1.19-2.10; p=0.0019); however, no significant differences were found for the risk of all-cause and cardiac death between normal weight and overweight patients. CONCLUSION: The results of the present long-term follow-up study do not support the so-called "obesity paradox," but rather, suggest that underweight Japanese patients are at greater risk for all-cause mortality following PCI.