An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention.

BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

Prevalence and Effects of High-Intensity Statins for Japanese Patients Presenting With Acute Coronary Syndrome　- A Post Hoc Secondary Analysis of STOPDAPT-2 ACS.

BACKGROUND: The REAL-CAD trial, reported in 2017, demonstrated a significant reduction in cardiovascular events with high-intensity statins in patients with chronic coronary syndrome. However, data are scarce on the use of high-intensity statins in Japanese patients with acute coronary syndrome (ACS).Methods and Results: In STOPDAPT-2 ACS, which exclusively enrolled ACS patients between March 2018 and June 2020, 1,321 (44.2%) patients received high-intensity statins at discharge, whereas of the remaining 1,667 patients, 96.0% were treated with low-dose statins. High-intensity statins were defined as the maximum approved doses of strong statins in Japan. The incidence of the cardiovascular composite endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke) was significantly lower in patients with than without high-intensity statins (1.44% vs. 2.69% [log-rank P=0.025]; adjusted hazard ratio [aHR] 0.48, 95% confidence interval [CI] 0.24-0.94, P=0.03) and the effect was evident beyond 60 days after the index percutaneous coronary intervention (log-rank P=0.01; aHR 0.38, 95% CI 0.17-0.86, P=0.02). As for the bleeding endpoint, there was no significant difference between the 2 groups (0.99% vs. 0.73% [log-rank P=0.43]; aHR 0.96, 95% CI 0.35-2.60, P=0.93). CONCLUSIONS: The prevalence of high-intensity statins has increased substantially in Japan. The use of the higher doses of statins in ACS patients recommended in the guidelines was associated with a significantly lower risk of the primary cardiovascular composite endpoint compared with lower-dose statins.

Low apolipoprotein A1 was associated with increased risk of cancer mortality in patients following percutaneous coronary intervention: A 10-year follow-up study.

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-C) predicted reduced risk of cardiovascular-related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single-center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow-up period between the index PCI and latest follow-up were 5.9 and 0-17.8 years, respectively. Consequently, Kaplan-Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL-C. Multivariable Cox proportional hazard regression analysis adjusted by cancer-related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.

Long-Term Outcomes in Elderly Patients After Deferral of Coronary Revascularization Guided by Fractional Flow Reserve.

BACKGROUND: Little evidence is available regarding the long-term outcome in elderly patients after deferral of revascularization based on fractional flow reserve (FFR).Methods and Results: From the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry), 1,262 patients were divided into 2 groups according to age: elderly and younger patients (aged ≥75 or <75 years, respectively). The primary endpoint was the cumulative 5-year incidence of target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Cumulative 5-year incidence of TVF was not significantly different between elderly and younger patients (14.3% vs. 10.8%, P=0.12). Cardiac death occurred more frequently in elderly patients than younger patients (4.4% vs. 0.8%, P<0.001), whereas TVMI and CDTVR did not differ between groups (1.3% vs. 0.9%, P=0.80; 10.7% vs. 10.1%, P=0.80, respectively). FFR values in lesions with diameter stenosis <50% were significantly higher in elderly patients than in younger patients (0.88±0.07 vs. 0.85±0.07, P=0.01), whereas this relationship was not observed in those with diameter stenosis ≥50%. CONCLUSIONS: Elderly patients had no excess risk of ischemic events related to the deferred coronary lesions by FFR, although FFR values in mild coronary artery stenosis were modestly different between elderly and younger patients.

Clinical features and predictors of outcome in patients with acute myocardial infarction complicated by out-of-hospital cardiac arrest.

BACKGROUND: Although short-term mortality of acute myocardial infarction (AMI) has decreased dramatically in the past few decades, sudden cardiac arrest remains a serious complication. The aim of the study was to assess the clinical characteristics and predictors of prognosis in AMI patients who experienced out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively registered consecutive AMI patients who were treated with emergency percutaneous coronary intervention (PCI) between 2004 and 2017. Clinical characteristics and outcomes were compared between patients with OHCA and those without OHCA. RESULTS: Among 2101 AMI patients, 95 (4.7%) presented with OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93-0.97; p < 0.0001), absence of diabetes mellitus (OR, 0.51; 95% CI, 0.30-0.85; p = 0.01) or dyslipidemia (OR, 0.56; 95% CI, 0.36-0.88; p = 0.01), left main trunk (LMT) or left anterior descending artery (LAD) as the culprit lesion (OR, 3.26; 95% CI, 1.99-5.33; p < 0.0001), and renal deficiency (OR, 3.64; 95% CI, 2.27-5.84; p < 0.0001) were significantly associated with incidence of OHCA. Thirty-day mortality was 32.6% in patients with OHCA and 4.5% in those without OHCA. Multivariate logistic analysis revealed LMT or LAD as the culprit lesion (OR, 12.18; 95% CI, 2.27-65.41; p = 0.004), glucose level (OR, 1.01; 95% CI, 1.00-1.01; p = 0.01), and renal deficiency (OR, 3.35; 95% CI, 1.07-10.53; p = 0.04) as independent predictors of 30-day mortality among AMI patients with OHCA. CONCLUSIONS: In patients with AMI who underwent emergency PCI, 30-day mortality was six times greater in those having presented initially with OHCA compared with those without OHCA. Younger age, absence of diabetes mellitus or dyslipidemia, LMT or LAD as the culprit lesion, and renal deficiency were independent predictors of OHCA. OHCA patient with higher blood glucose level on admission, LMT or LAD as the culprit lesion, or renal deficiency showed worse clinical outcomes.

Red Cell Distribution Width Predicts Long-Term Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

Red cell distribution width (RDW) has been shown to be an independent risk factor for increased cardiovascular mortality, heart failure, and cardiovascular disease. However, the association between RDW and long-term clinical outcomes in patients with chronic coronary syndrome (CCS) remains uncertain. In this study, a total of 2,881 CCS patients who underwent their first percutaneous coronary intervention (PCI) and who had available data on pre-procedural RDW between 2002 and 2016 were enrolled. Of these, 1,827 without anemia and severe renal dysfunction were divided into quartiles based on their RDW values. The primary endpoint was a composite of all-cause death and non-fatal myocardial infarction. As a result, patients in the higher RDW quartile groups were more likely to be older and have chronic kidney disease. During a median follow-up of 6.2 years, 209 (11.4%) events were identified. Kaplan-Meier curves showed the highest RDW quartile group had a clearly higher incidence of the primary endpoint (log-rank P = 0.0002). The highest RDW group had a significantly higher risk of cardiovascular events compared with the lowest RDW group, even after adjustment for other risk factors (hazard ratio 1.95, 95% confidence interval 1.04-3.67, P = 0.04). Increasing RDW as a continuous variable was also associated with the incidence of the primary endpoint (hazard ratio 1.46 per 1% increase, 95% confidence interval 1.24-1.69, P < 0.0001). In conclusion, this study demonstrated that increased RDW was associated with worse clinical outcomes after elective PCI. Assessing pre-PCI RDW may be useful for risk stratification of CCS.

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.

Clinical Characteristics and Long-Term Outcomes of Patients with Acute Coronary Syndrome During Travel.

Cardiovascular disease is a major cause of death among travelers, but the clinical characteristics and clinical outcomes of patients who develop acute coronary syndrome (ACS) while traveling have not been assessed. We evaluated 2548 patients with ACS who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 and compared the incidences of all-cause and cardiac death during follow-up between travelers and locals. We assessed 192 (7.5%) patients who developed ACS while traveling. These patients were younger and had a higher prevalence of ST-elevation myocardial infarction than local patients. During a median follow-up period of 5.3 years, 632 (24.8%) all-cause deaths were identified, including 310 cardiac deaths (12.2%). Kaplan-Meier analysis revealed that the cumulative incidence of all-cause death was significantly lower among the travelers than locals (P = 0.001, log-rank test). Multivariate Cox hazard analysis revealed that travel was significantly associated with a lower rate of all cause death (hazard ratio, 0.53; 95% confidence interval, 0.33-0.80; P = 0.002). Cardiac mortality did not significantly differ between travelers and locals (P = 0.29). Patients with ACS treated with primary PCI while traveling had more favorable long-term clinical outcomes than local patients. Appropriate initial treatments and secondary preventions might improve the prognosis of travelers.

Long-Term Clinical Impact of Cardiogenic Shock and Heart Failure on Admission for Acute Myocardial Infarction.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.

Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c < 6.5%) in Japanese medically-treated diabetic patients following percutaneous coronary intervention: a 10-year follow-up study.

BACKGROUND: In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5-7.0% (n = 268), 7.0-7.5% (n = 262), 7.5-8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. RESULTS: In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan-Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0-7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0-7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0-7.5%: 2.97, 95% confidence interval: 1.33-7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0-7.5% group. CONCLUSION: The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes. Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).

Impact of LR11 as Residual Risk on Long-Term Clinical Outcomes in Patients with Coronary Artery Disease Treated with Statins after First Percutaneous Coronary Intervention.

Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.

Neutrophil to Lymphocyte Ratio and Long-Term Cardiovascular Outcomes in Coronary Artery Disease Patients with Low High-Sensitivity C-Reactive Protein Level.

Although an elevated neutrophil to lymphocyte ratio (NLR) has been associated with the adverse outcomes of coronary artery disease (CAD), less is known about its prognostic value among patients with low high-sensitivity C-reactive protein (hs-CRP) levels. We enrolled 2,591 consecutive patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) and had available data on preprocedural hs-CRP and NLR between 2000 and 2016. Of these patients, 1,951 with low-grade hs-CRP levels (< 2.0 mg/L) were divided into quartiles based on the NLR values. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke after the index PCI. Clinical follow-up data were obtained up to 5 years. The median NLR was 1.9 (interquartile range: 1.5-2.5). During the follow-up, 102 events occurred (5.2%), with a cumulative incidence that was significantly higher in the highest NLR group than in the other groups (log-rank, P = 0.02). After adjusting for the other cardiovascular risk factors, the risk for the primary endpoint was significantly higher for the highest than in the lowest NLR group (HR 1.97, 95% CI 1.09-3.54, P = 0.02). Increasing NLR as a continuous variable was associated with the incidence of adverse cardiovascular events (HR 1.85 per log 1 NLR increase, 95% CI 1.19-2.88, P = 0.007). In conclusion, the adverse long-term clinical outcomes of CAD patients with low-grade hs-CRP levels has been independently predicted by increased NLR level. NLR could be useful for risk stratification of CAD patients with increased inflammatory marker levels.

Prognostic Impact of B-Type Natriuretic Peptide on Long-Term Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Myocardial Infarction Without Creatine Kinase Elevation.

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.

Admission During Off-Hours Does Not Affect Long-Term Clinical Outcomes of Japanese Patients with Acute Myocardial Infarction.

Discordant results have been reported on outcomes of acute myocardial infarction (AMI) patients who present during off-hours.We investigated 3283 consecutive patients with AMI who were selected from the prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation (defined as weekends, holidays, and weekdays from 8:01 PM to 7:59 AM) at hospitals on long-term clinical outcomes. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina for up to 3 years from the index event.During off-hours, 52% of patients presented. Primary percutaneous coronary intervention was performed in 85% of patients, and the door-to-balloon time was comparable between off-hours and regular hours (74, interquartile range [IQR] 52 to 113 versus 75, IQR 52 to 126 minutes, P = 0.34). Rate of overall primary endpoint overall did not overall significantly differ (25.3% versus 23.5%, log-rank P = 0.26), in patients with ST-elevation myocardial infarction (STEMI) (log-rank P = 0.93) and in patients with non-ST-elevation myocardial infarction (NSTEMI) (log-rank P = 0.14). Multivariate Cox regression analysis showed that off-hours presentation was not significantly associated with long-term clinical events in all cohorts.The impact of presentation during off-hours or regular hours on the long-term clinical outcomes of Japanese patients with AMI is comparable in contemporary practice.

Impact of serum 1,5-anhydro-D-glucitol level on the prediction of severe coronary artery calcification: an intravascular ultrasound study.

BACKGROUND: A low 1,5-anhydro-D-glucitol (AG) blood level is considered a clinical marker of postprandial hyperglycemia. Previous studies reported that 1,5-AG levels were associated with vascular endothelial dysfunction and coronary artery disease (CAD). However, the association between 1,5-AG levels and coronary artery plaque in patients with CAD is unclear. METHODS: This study included 161 patients who underwent percutaneous coronary intervention for CAD. The culprit plaque characteristics and the extent of coronary calcification, which was measured by the angle of its arc, were assessed by preintervention intravascular ultrasound (IVUS). Patients with chronic kidney disease or glycosylated hemoglobin ≥ 7.0 were excluded. Patients were divided into 2 groups according to serum 1,5-AG levels (< 14.0 µg/mL vs. ≥ 14 µg/mL). RESULTS: The total atheroma volume and the presence of IVUS-attenuated plaque in the culprit lesions were similar between groups. Calcified plaques were frequently observed in the low 1,5-AG group (p = 0.06). Compared with the high 1,5-AG group, the low 1,5-AG group had significantly higher median maximum calcification (144° vs. 107°, p = 0.03) and more frequent calcified plaques with a maximum calcification angle of ≥ 180° (34.0% vs. 13.2%, p = 0.003). Multivariate logistic regression analysis showed that a low 1,5-AG level was a significant predictor of a greater calcification angle (> 180°) (OR 2.64, 95% CI 1.10-6.29, p = 0.03). CONCLUSIONS: Low 1,5-AG level, which indicated postprandial hyperglycemia, was associated with the severity of coronary artery calcification. Further studies are needed to clarify the effects of postprandial hyperglycemia on coronary artery calcification.

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.

Clinical Significance of High-Sensitivity C-Reactive Protein in Patients with Preserved Renal Function Following Percutaneous Coronary Intervention.

Although 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 interventions (PCIs), little is known about the association between hs-CRP and long-term outcomes in patients with preserved renal function.Here, we studied 1,153 patients with stable CAD and preserved renal function (estimated glomerular filtration rate: > 60 mL/minute/1.73 m2) who underwent their first PCI between 2000 and 2011. Those with available data on preprocedural hs-CRP were included. Patients were assigned to tertiles according to preprocedural hs-CRP levels. The incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction, was evaluated. During a median follow-up period of 7.5 years, Kaplan-Meier curves showed ongoing divergence in the rates of MACE among the hs-CRP tertiles (hs-CRP < 0.05 mg/L, 12.1%; 0.05-0.17 mg/L, 12.1%; > 0.17 mg/L, 21.6%; log-rank P = 0.003). After adjusting for the established cardiovascular risk factors, hs-CRP levels were found to be associated with a higher incidence of MACE (hazard ratio [HR]: 3.65, 95% confidence interval [CI]: 1.77-7.07; P = 0.0008) and a higher rate of all-cause mortality (HR: 5.14, 95% CI: 2.38-10.30; P < 0.0001).In conclusion, this long-term registry showed that preprocedural hs-CRP measurement is clinically useful for long-term risk assessments in patients with stable CAD and preserved renal function.

Combined effect of nutritional status on long-term outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention.

Previous studies have reported the prognostic value of objective nutritional indices such as the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI). However, the effects of these indices in patients with coronary artery disease (CAD) who have undergone percutaneous coronary intervention (PCI) remain unclear. Furthermore, there are insufficient data to combine these indices. A total of 1984 patients who underwent elective PCI were enrolled. The Combined Objective Nutritional Score was determined by assigning 1 point each for high CONUT score (3-12), low GNRI (< 98) or low PNI (< 45). Patients were grouped into normal nutritional status (0 points), mild-to-moderate malnutrition (1-2 points) and severe malnutrition (3 points). Incidences of all-cause death and cardiac death were evaluated. Among the 1984 patients, 514 (25.9%) and 244 (12.3%) had mild-to-moderate and severe malnutrition, respectively. During follow-up (median 7.4 years), 293 all-cause deaths were identified, including 92 cardiac deaths. Kaplan-Meier curves showed ongoing divergence in rates of death among nutritional statuses determined by the novel score (log rank test, p < 0.0001). Multivariate Cox hazard analysis showed that patients with a Combined Objective Nutritional Score of 3 showed 2.91-fold (95% confidence interval (CI) 2.10-4.00; p < 0.0001) and 2.16-fold (95% CI 1.15-3.92; p = 0.02) increases in risk of mortality and cardiac mortality compared with patients with a Combined Objective Nutritional Score of 0. In conclusion, malnutrition as evaluated by the Combined Objective Nutritional Score was significantly associated with worse long-term cardiovascular outcomes among CAD patients who underwent PCI.