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).

Major bleeding increases the risk of subsequent cardiovascular events in patients with atrial fibrillation: insights from the SAKURA AF registry and RAFFINE registry.

BACKGROUND: Bleeding events are one of the major concerns in patients using oral anticoagulants (OACs). We aimed to evaluate the association between major bleeding and long-term clinical outcomes in atrial fibrillation (AF) patients taking OACs. METHODS: We analyzed a database comprising two large-scale prospective registries of patients with documented AF: the RAFFINE and SAKURA registries. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, ischemic stroke, and myocardial infarction. Major bleeding was defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis. Cox multivariate analysis was used to determine the impact of major bleeding on the incidence of MACCE. RESULTS: The median follow-up period was 39.7 (interquartile range, 33.1-48.1) months. Among 6,633 patients with AF who were taking OAC, 298 (4.5%) had major bleeding and 737 (11.1%) had MACCE. The incidence of MACCE was higher in patients with bleeding than in those without (18.33 and 3.22, respectively, per 100 patient-years; log-rank p < 0.0001). Multivariate logistic regression analysis revealed older age, vitamin K antagonist use, and antiplatelet drug use as independent predictors of major bleeding. Median duration of MACCE occurrence after major bleeding was 41 (interquartile range, 3-300) days. Multivariate Cox hazard regression analysis showed that the risk of MACCE was significantly higher in patients with major bleeding compared to those without (hazard risk, 4.64; 95% confidence interval, 3.62-5.94; p < 0.0001). CONCLUSIONS: Major bleeding was associated with long-term adverse cardiovascular events among AF patients taking OAC. Therefore, reducing the risk of bleeding is important for improving clinical outcomes in patients with AF.

Characteristics and outcomes of patients with no standard modifiable risk factors undergoing primary revascularization for acute myocardial infarction: Insights from the nationwide Japanese percutaneous coronary intervention registry.

BACKGROUND: Identification of and therapeutic approaches to standard modifiable risk factors (SMuRFs), including hypertension, diabetes, dyslipidemia, and smoking, have led to improved survival of patients at risk for coronary events. However, recent studies have indicated that a significant proportion of patients with acute myocardial infarction (AMI) have no SMuRFs. We aimed to assess in-hospital outcomes and the prevalence of these patients using the Japanese nationwide percutaneous coronary intervention (J-PCI) registry. METHODS: The J-PCI is a procedure-based registration program in Japan. A total of 115,437 PCI procedures were performed on patients with AMI between January 2019 and December 2020. The participants were divided into 2 groups: those with at least 1 SMuRF and those without any SMuRFs. The primary outcome was in-hospital mortality. RESULTS: Of the 115,437 patients with AMI, 1,777 (1.6%) had no SMuRFs. Patients without SMuRFs were older; more likely to have left main disease; and more likely to present with heart failure, cardiogenic shock, and cardiac arrest than those with SMuRFs, resulting in higher rates of mechanical circulatory support use and impaired post-PCI coronary blood flow. In-hospital mortality was significantly higher in patients without SMuRFs than in those with SMuRFs (18.3% vs 5.3%, P < .001), irrespective of the presence or absence of ST-segment elevation. CONCLUSIONS: In Japan, where annual health checks are mandated under universal health care coverage, the vast majority of patients with AMI undergoing PCI have SMuRFs. However, although small in number, patients without SMuRFs are more likely to present with life-threatening conditions and have worse in-hospital survival.

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.

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).

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.

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.

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.

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.