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).

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.

Blocking of interleukin-1 suppresses angiotensin II-induced renal injury.

Clinical hypertension (HT) is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. Interleukin (IL)-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the Angiotensin II (Ang II)-induced HT response. The present study aimed to elucidate the effects of IL-1Ra and anti-IL-1ß antibody (01BSUR) on Ang II-induced renal injury. To determine the contribution of IL-1Ra to Ang II-induced renal inflammation, male wildtype (WT) and IL-1Ra-deficient (IL-1Ra-/-) mice were infused with Ang II (1000 ng/kg/min) using subcutaneous osmotic pump for 14 days. We checked renal function, histological change, and several mRNA expressions 14 days after infusion. Fourteen days after infusion, systolic blood pressure (197 ± 5 vs 169 ± 9 mmHg, P<0.05) in IL-1Ra-/- mice significantly increased compared with WT mice. Furthermore, on day 14 of Ang II infusion, plasma IL-6 was 5.9-fold higher in IL-1Ra-/- versus WT mice (P<0.001); renal preproendothelin-1 mRNA expression was also significantly higher in IL-1Ra-/- mice (P<0.05). In addition, renal histology revealed greater damage in IL-1Ra-/- mice compared with WT mice 14 days after infusion. Finally, we administrated 01BSUR to both IL-1Ra-/- and WT mice, and 01BSUR treatment decreased Ang II-induced HT and renal damage (glomerular injury and fibrosis of the tubulointerstitial area) in both IL-1Ra-/- and WT mice compared with IgG2a treatment. Inhibition of IL-1 decreased Ang II-induced HT and renal damage in both IL-1Ra-/- and WT mice, suggesting suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients.

Comparison of 6-month vascular healing response after bioresorbable polymer versus durable polymer drug-eluting stent implantation in patients with acute coronary syndromes: A randomized serial optical coherence tomography study.

OBJECTIVES: This study was conducted to use optical coherence tomography (OCT) to compare vascular healing between bioresorbable polymer (BP) and durable polymer (DP) everolimus-eluting stents (EES) in patients with acute coronary syndromes (ACS). BACKGROUND: Whether BP-EES induce better vascular healing compared to contemporary DP-EES remains controversial, especially for ACS. METHODS: In this prospective, randomized, non-inferiority trial, we used OCT to compare 6-month vascular healing in patients with ACS randomized to BP versus DP-EES: percent strut coverage (primary endpoint, non-inferiority margin of 2.0%) and neointimal thickness and percent neointimal hyperplasia (NIH) volume. As an exploratory analysis, morphological factors related to the endpoints and the effect of underlying lipidic plaque on stent healing were evaluated. RESULTS: A total of 104 patients with ACS were randomly assigned to BP-EES (n = 52) versus DP-EES (n = 52). Of these, 86 patients (40 BP-EES and 46 DP-EES) were included in the final OCT analyses. Six-month percent strut coverage of BP-EES (83.6 ± 11.4%) was not non-inferior compared to those of DP-EES (81.6 ± 13.9%), difference 2.0% (lower 95% confidence interval-2.6%), pnon-inferiority  = 0.07. There were no differences in neointimal thickness 70.0 ± 33.9 µm versus 67.2 ± 33.9 µm, p = 0.71; and percent NIH volume 7.5 ± 4.7% versus 7.3 ± 5.3%, p = 0.85. By multivariable linear regression analysis, stent type was not associated with percent strut coverage or percent NIH volume; however, percent baseline embedded struts or stent expansion was positively associated with percent NIH volume. Greater NIH volume was observed in lipidic compared with non-lipidic segments (8.7 ± 5.6% vs. 6.1 ± 5.2%, p = 0.005). CONCLUSIONS: Six-month strut coverage of BP-EES was not non-inferior compared to those of DP-EES in ACS patients. Good stent apposition and expansion were independently associated with better vascular healing.

Long-term impact of high-sensitivity C-reactive protein in patients with intermittent claudication due to peripheral artery disease following endovascular treatment.

Little is known about the prognostic impact of high-sensitivity C-reactive protein (hs-CRP) levels on causes of death during long-term follow-up. We, therefore, investigated the associations between hs-CRP and clinical outcomes in the patients with intermittent claudication. Three hundred thirty-five consecutive patients (mean age, 72 ± 8 years, 82% men) undergoing first intervention for de novo iliac and/or femoropopliteal artery lesions from 2009 to 2020 were studied. Patients were divided into 2 groups based on the optimal cutoff value of hs-CRP (> or ≤ 0.15 mg/dL). The median follow-up duration was 3.6 years (interquartile range, 1.0-6.2 years). Although the cumulative incidence rate of major adverse cardiovascular limb events was not significantly different between the higher and lower hs-CRP groups (29.0 and 22.1%, respectively; log-rank test, p = 0.410), that of all-cause death was significantly higher in the higher hs-CRP group than in the lower hs-CRP group (18.7 vs. 5.8%, log-rank test, p = 0.007), even in cardiovascular-related death and malignancy-related death (log-rank test, p = 0.030 and 0.046, respectively). Higher hs-CRP levels at the time of intervention were significantly associated with higher frequency of all-cause death, even after adjusting for other risk factors (hazard ratio 2.79; 95% confidence interval 1.66-7.17, p = 0.024). In addition, malignancy-related death was most frequent as high as 60% (21/35 deaths), and elevated hs-CRP levels and the Brinkman index were strongly independent predictors of malignancy-related death. In conclusion, elevated hs-CRP levels were significantly associated with cardiovascular-related and malignancy-related deaths in patients with intermittent claudication. Furthermore, the result that cancer mortality exceeds cardiovascular mortality is different from previous reports, so the present findings warrant further investigation.

The prognostic implications of chronic kidney disease and anemia on long-term outcomes in patients undergoing percutaneous coronary intervention.

Chronic kidney disease (CKD) and anemia are each individually associated with worse clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of both CKD and anemia on clinical outcomes, when they coexist, remains unclear in CAD patients after percutaneous coronary intervention (PCI). We studied 2484 CAD patients who underwent their first PCI and had available date on preprocedural hemoglobin between 2000 and 2016. The patients were divided into four groups according to the presence of CKD and/or anemia. We evaluated the incidences of all-cause death and major adverse cardiac and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction, and stroke. Among the patients, 310 patients (12.5%) had both CKD and anemia (CKD with anemia group), 309 (12.4%) had CKD only, 461(18.6%) had anemia only, and 1404 (56.5%) had neither CKD nor anemia. Patients in the CKD with anemia group were older and had a higher incidence of hypertension and diabetes mellitus. During a median follow-up period of 3.7 years, Kaplan-Meier curves showed that patients in the CKD with anemia group had significantly higher incidences of MACCE and all-cause death than the CKD only and anemia only group (both log-rank p < 0.001). Using patients with the no CKD or anemia group as a reference, the adjusted hazard ratios (HRs), 95% confidence interval for MACCE were 1.51 (0.92-2.47) for the CKD only, 1.48 (0.94-2.32) for the anemia only and 2.00 (1.18-3.38) for the CKD with anemia group. Moreover, the adjusted HR for all-cause death were 1.42 (0.96-2.10) for the CKD only, 1.79 (1.28-2.51) for the anemia only, and 1.92 (1.30-2.84) for the CKD with anemia group. In conclusion, the combined effects of both CKD and anemia on outcomes after PCI were worse than either of their individual effects.

High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment.

Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.

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).

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.

Reduced Number of Platelets During Intra-Aortic Balloon Pumping Counterpulsation Predicts Higher Cardiovascular Mortality After Device Removal in Association with Systemic Inflammation.

Thrombocytopenia is a frequent complication in patients requiring intra-aortic balloon pumping (IABP) counterpulsation. However, its prognostic impact has not been fully addressed. The objective of this study is to evaluate the impact of the change in the platelet number during IABP use on the prognosis after device removal.This is a retrospective observational study. Patients in the intensive cardiac care unit at three Juntendo University hospitals who underwent percutaneous implantation of IABP with or without veno-arterial extracorporeal membrane oxygenation (V-A ECMO), since 2012-2016, were enrolled in the study (n = 439). Patients who died during mechanical circulatory support (n = 47) were excluded. We evaluated the prognostic impact of the ratio of platelet reduction from the baseline (% PLT reduction) during IABP use on cardiovascular mortality after device removal.The median and the range of follow-up period were 298 days and 0-1,869 days, respectively. Unadjusted Kaplan-Meier analysis demonstrated that patients with a higher % PLT reduction had higher cardiovascular (CV) mortality. An adjusted Cox proportional hazard analysis demonstrated that a 10% higher % PLT reduction was associated with higher cardiovascular (CV) mortality (Hazard ratio: 1.3, 95% Confidence interval: 1.1-1.6, P < 0.001). Moreover, % PLT reduction and the maximum C-reactive protein (CRP) level during IABP use were positively correlated (r = 0.326, P < 0.001).The reduced number of platelets during IABP use was associated with an increased risk of CV mortality.

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.

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.

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.

Acute Coronary Syndrome Evacuated by a Helicopter From the Scene.

OBJECTIVE: The purpose of this study was to investigate the safety of evacuating patients using a physician-staffed helicopter (Dr. Heli). METHODS: We retrospectively investigated all of the patients with acute coronary syndrome (ACS) who were transported by a Dr. Heli between April 2004 and March 2016. The scene group included subjects evacuated from the scene by the Dr. Heli. The interhospital group included subjects transported to a nearby medical facility by a ground ambulance and then transported to our hospital by a Dr. Heli. RESULTS: The scene and interhospital groups included 170 subjects and 592 subjects, respectively. There were no significant differences between the 2 groups with regard to sex and survival ratios. However, the patients in the scene group were significantly younger than those in the interhospital group. The ratio of prehospital cardiopulmonary arrest in the scene group was significantly higher than in the interhospital group. After excluding subjects who were over 80 years of age, there were no significant differences between the 2 groups with regard to age. However, the same tendencies remained. CONCLUSION: This result indirectly suggests the safety of using the Dr. Heli to evacuate ACS patients from the scene.

Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention.

BACKGROUND: Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG level on cardiovascular events has not been fully investigated. METHODS: We enrolled 240 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1 year. We excluded patients with a history of acute coronary syndrome, advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), or uncontrolled diabetes mellitus (HbA1c ≥7.0 %). Fasting blood glucose (FBS), HbA1c, and 1,5-AG levels were measured prior to PCI and at the time of follow-up angiography. Clinical events, including target lesion revascularization, target vessel revascularization, and revascularization of new lesions, were evaluated. RESULTS: Subjects were divided into two groups according to clinical outcomes: the Event (+) group (n = 40) and the Event (-) group (n = 200). No significant differences were observed, except for the number of diseased vessels and the prevalence of statin use, in baseline clinical characteristics between the two groups. Serum levels of 1,5-AG at follow-up were significantly lower in the Event (+) group than in the Event (-) group (P = 0.02). A significant reduction in 1,5-AG level from baseline to follow-up was observed in the Event (+) group compared with the Event (-) group (P = 0.04). The association between 1,5-AG levels at follow-up and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P = 0.04). CONCLUSIONS: Low and exacerbated levels of 1,5-AG were associated with cardiovascular events in the present study, indicating that postprandial hyperglycemia is an important risk factor for adverse clinical events even in patients with HbA1c < 7.0 %, following first-time elective PCI.

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.