The Association Between Serum Uric Acid and Mortality in Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m2; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.

Impact of concomitant peripheral artery disease on contrast-induced acute kidney injury and mortality in patients with acute coronary syndrome after percutaneous coronary intervention.

Subclinical peripheral artery disease (PAD) might be associated with pathophysiology of contrast-induced acute kidney injury (CI-AKI). We hypothesized that concomitant PAD in patients with the acute coronary syndrome (ACS) would represent a high-risk subgroup with a greater incidence of CI-AKI, both of which lead to higher mortality after percutaneous coronary intervention (PCI). Six hundred and seventy-five consecutive patients with ACS who underwent PCI and examination of ankle-brachial index (ABI) were analyzed retrospectively. The presence of PAD was defined as an ABI < 0.9. We investigated whether (1) PAD was an independent predictor of CI-AKI (≥ 0.3 mg/dL or ≥ 50% relative increase in serum creatinine within 48 h after PCI) and (2) PAD and CI-AKI were independently associated with long-term mortality. Of the 675 patients with ACS, 114 (17%) exhibited PAD. The incidence of CI-AKI was significantly higher in PAD patients, compared with the remaining patients (12% vs. 4%, p < 0.001). Multivariate logistic regression analysis revealed that the presence of PAD was an independent predictor for the development of CI-AKI [odds ratio 2.50, 95% confidence interval (CI) 1.07-5.73, p < 0.05]. During the median 4-year follow-up, there were 65 incidents of all-cause death. In the multivariate Cox proportional hazard regression analysis, the presence of PAD [hazard ratio (HR) 2.08, 95% CI 1.17-3.65, p < 0.05] and CI-AKI (HR 2.23, 95% CI 1.08-4.26, p < 0.05) were associated with an increased risk of all-cause mortality. Assessment of ABI provides useful information for predicting CI-AKI and long-term mortality in patients with ACS after PCI.

Paradoxical impact of decreased low-density lipoprotein cholesterol level at baseline on the long-term prognosis in patients with acute coronary syndrome.

Although statin therapy is beneficial in the setting of acute coronary syndrome (ACS), a substantial proportion of patients with ACS still do not receive the guideline-recommended lipid management in contemporary practice. We hypothesize that the low-density lipoprotein cholesterol (LDL-C) level at the time of admission might affect patient management and the subsequent outcome. Nine-hundred and forty-two consecutive patients with ACS who underwent percutaneous coronary intervention were analyzed retrospectively. The study patients were first divided into two groups based on the LDL-C level on admission: group A (n = 267), with LDL-C < 100 mg/dL; and group B (n = 675), with LDL-C ≥ 100 mg/dL. Each group was then further divided into those who were prescribed statins or not at the time of discharge from the hospital. The primary endpoint was all-cause death. In addition, we analyzed the serial changes of LDL-C within 1 year. Patients in group A were significantly older and more likely to have multiple comorbidities compared with group B. The proportion of patients who were prescribed statin at discharge was significantly smaller in group A compared with group B (57.7 vs. 77.3%, p < 0.001). During the median 4-year follow-up, there were 122 incidents of all-cause death. Multivariate Cox proportional hazard analysis revealed that LDL-C < 100 mg/dL on admission [hazard ratio (HR), 1.61; 95% confidence interval (CI), 1.09-2.39; p < 0.05] and prescription of statins at discharge (HR, 0.52; 95% CI, 0.36-0.76; p < 0.001) were associated significantly with all-cause death. Under these conditions, increasing LDL-C levels were documented during follow-up in those patients in group A when no statins were prescribed at discharge (79 ± 15-96 ± 29 mg/dL, p < 0.001), whereas these remained unchanged when statins were prescribed at discharge (79 ± 15-77 ± 22 mg/dL, p = 0.30). These results demonstrate that decreased LDL-C on admission in ACS led to less prescription for statins, which could result in increased death, probably due to underestimation of the baseline LDL-C.

Early endothelialization associated with a biolimus A9 bioresorbable polymer stent in a porcine coronary model.

Although Nobori®, with a bioresorbable polymer and biolimus A9 abluminal coating, has unique characteristics, few data exist regarding endothelialization early after implantation. Fifteen Nobori® and 14 control bare-metal stents (S-stent™) were implanted in 12 pigs. Histopathology of stented segments, inflammation, and intimal fibrin content was evaluated on the 2nd and 14th day after implantation. On the 2nd day, endothelial cells were morphologically and immunohistologically confirmed on the surface of both stents, although some inflammatory cells might be involved. Stent surface endothelialization evaluated with a scanning electron microscope showed partial cellular coverage in both stents. On the 14th day, neointimal thickness and percentage of the neointimal area were significantly lower in Nobori® than in S-stent™ (51.4 ± 4.5 vs. 76.4 ± 23.6 µm, p < 0.05 and 10.8 ± 2.6 vs. 14.1 ± 4.2%, p < 0.01). No significant differences were found in these parameters on the 2nd day (17.3 ± 14.9 vs. 26.7 ± 13.6 µm and 3.7 ± 3.0 vs. 6.7 ± 3.7%), in inflammatory and intimal fibrin content scores. These results demonstrate that endothelialization could occur early after Nobori® implantation with similar inflammatory reaction to bare-metal stents, probably contributing to low frequency of in-stent thrombosis and restenosis.

Short- and long-term benefits of drug-eluting stents compared to bare metal stents even in treatment for large coronary arteries.

Although drug-eluting stents (DES) for percutaneous coronary intervention (PCI) have dramatically reduced the incidence of in-stent restenosis, their deployment for large-size coronary lesions is still controversial because of problems such as late in-stent thrombosis and late catch-up in DES. We aimed to evaluate the long-term outcome beyond 2 years of bare metal stents (BMS) as compared with DES in large vessels. Consecutive 228 patients who underwent PCI with large-size stents (>3.5 mm in diameter) in our hospital were enrolled in this study. The end points of this study are target lesion revascularization (TLR) and occurrence of major adverse cardiac events (MACE) for subject patients. We analyzed 183 patients (152 men, mean age 65.8 ± 10.5 years) whose outcome could be followed up for at least 2 years. At the first 8-month follow-up, clinically driven TLR rate was significantly higher in patients who received BMS than those who received DES (17.2 vs. 2.2 %, p < 0.05), although the rate of TLR was not different between the 2 groups beyond 8 months. Thus, overall rate of TLR was higher in BMS than in DES (22.7 vs. 5.4 %, p < 0.05). Under these conditions, the higher rate of TLR for BMS was observed in simple as well as complex lesions with or without diabetes, although there were no significant differences in MACE between BMS and DES. Multivariate analysis showed that BMS was an only independent factor of TLR at the 8 month follow-up period [p = 0.004, odds ratio 9.58, 95 % confidence interval (2.10-43.8)]. These results demonstrate that the rate of in-stent restenosis in large-size coronary lesions was transiently higher in the first 8 months for patients implanted with BMS compared with DES in which no in-stent thrombosis and TLR beyond 2 years were observed. We suggest using the DES even in large-size coronary lesions in terms of short- and long-term outcomes.

Successful Endovascular Treatment of Calcified Superior Mesenteric Artery Complicated by Intramural Hematoma in Chronic Mesenteric Ischemia.

BACKGROUND Chronic mesenteric ischemia (CMI) is defined as ischemic symptoms caused by insufficient supply of blood to the gastrointestinal tract. Patients diagnosed with advanced symptomatic CMI should be treated subsequently, as the transition from CMI to acute mesenteric ischemia can be unpredictable. However, there is little information regarding the management of potential procedural complications during endovascular therapy (EVT) for CMI. CASE REPORT A 70-year-old man was admitted to our hospital with recurrent abdominal pain just after hemodialysis. The angiogram showed significant stenosis with heavy calcification in the proximal of the superior mesenteric artery (SMA), leading to the diagnosis of CMI. To alleviate the symptom, EVT for the stenotic lesion of the SMA was indicated. During the procedure, a cutting balloon was inflated to facilitate vessel expansion in the target lesion. As a result, intravascular ultrasound (IVUS) imaging revealed dissection into the media with extension into the medial space without reentry and demonstrated a semilunar intramural hematoma. We were able to contain the intramural hematoma by covering the whole dissection in the SMA with implantation of self-expandable stents. CONCLUSIONS This case highlights the potential of EVT for heavy calcification of the SMA complicated by dissection without reentry. Intramural hematoma was observed with IVUS examination. We were able to contain the hematoma by the implantation of self-expandable stents over the whole length of the SMA dissection under IVUS-guided EVT.

Impact of hyperuricemia on coronary blood flow and in-hospital mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI). METHODS: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow grade ≤ 2. The secondary outcome was in-hospital mortality. RESULTS: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, p < 0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18 mg/dL; IQR, 0.09-0.71 mg/dL) than in those without (0.14 mg/dL; IQR, 0.07-0.41 mg/dL, p < 0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, p < 0.05) and in-hospital mortality (10.8% vs. 3.6%, p < 0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; p < 0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; p < 0.05). CONCLUSIONS: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI.

Comparison of Door-to-Balloon Time and 30-Day Mortality According to Symptom Presentation in Patients With Acute Myocardial Infarction.

Background: We hypothesized that symptom presentation in patients with acute myocardial infarction (AMI) may affect their management and subsequent outcome. Methods and Results: Using Rural AMI Registry data, 1,337 consecutive patients with AMI who underwent percutaneous coronary intervention were analyzed. Typical symptoms were defined as any symptoms of chest pain or pressure due to myocardial ischemia. We considered the specific symptoms of dyspnea, nausea, or vomiting as atypical symptoms. The primary outcome was 30-day mortality. There were 150 (11.2%) and 1,187 (88.8%) patients who presented with atypical and typical symptoms, respectively. Those who presented with atypical symptoms were significantly older (mean [±SD] age 74±12 vs. 68±13 years; P<0.001) and had a higher Killip class (46.7% vs. 21.8%; P<0.001) than patients presenting with typical symptoms. The prevalence of door-to-balloon time of ≤90 min was significantly lower in patients with atypical than typical symptoms (40.0% vs. 66.3%; P<0.001). At 30 days, there were 55 incidents of all-cause death. Multivariate Cox proportional hazards regression analysis revealed that symptom presentation was associated with 30-day mortality (hazard ratio 2.33; 95% confidence interval 1.20-4.38; P<0.05). Conclusions: Atypical symptoms in patients with AMI are less likely to lead to timely reperfusion and are associated with increased risk of 30-day mortality.

Clinical Impact of Carotid Plaque Score rather than Carotid Intima-Media Thickness on Recurrence of Atherosclerotic Cardiovascular Disease Events.

AIM: Carotid plaque score (cPS) reflecting throughout the carotid artery plaque burden may be a better marker than carotid intima-media thickness (cIMT) is. We aimed to compare the prognostic utility of these measurements in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: We retrospectively examined 2,035 Japanese patients with ASCVD who underwent carotid ultrasonography between January 2008 and December 2015 at Kanazawa University Hospital. Median follow-up period was 4 years. We used Cox models that adjusted for established risk factors of ASCVD, including age, gender, hypertension, diabetes, smoking, and serum lipids to assess the association of cIMT as well as cPS with major adverse cardiac events (MACE). MACE was defined as all-cause mortality or rehospitalization for a cardiovascular-related illness. RESULTS: During follow-up, 243 participants experienced MACE. After adjustment for established risk factors, cPS was associated with MACE (hazard ratio [HR]=3.38 for top quintile vs. bottom quintile of cPS; 95% confidence interval [CI] 1.82-6.27; P trend ＜0.001), while cIMT was not (HR=0.88, P=0.57). Addition of the cPS to established risk factors significantly improved risk discrimination (C-index 0.726 vs. 0.746; P=0.017). CONCLUSION: These results suggest that cPS, rather than cIMT may be a better marker to identify increased risk for recurrence of MACE among patients with secondary prevention setting.

Antegrade Balloon Aortic Valvuloplasty for the Highly Frail Patient of Severe Aortic Stenosis Complicated with Transthyretin-type Cardiac Amyloidosis.

Transcatheter aortic valve implantation (TAVI) is widely accepted as the treatment for patient with severe aortic stenosis (AS) whose prognosis may be over one year; however, there is no consensus concerning extremely high-risk patients whose prognosis may not exceed one year. We herein report a highly frail patient with severe AS complicated with transthyretin-type cardiac amyloidosis who had a very poor prognosis. Given his condition, we treated him by percutaneous antegrade balloon aortic valvuloplasty (A-BAV) instead of TAVI. A-BAV may be a beneficial option for treating extremely high-risk severe AS patients, including those with cardiac amyloidosis.

Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds. METHODS AND ANALYSIS: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies. ETHICS AND DISSEMINATION: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000038210.

Outcome of Patients With Prior Stroke/Transient Ischemic Attack and Acute Coronary Syndromes.

The association between prior stroke/transient ischemic attack (TIA) and clinical outcomes in patients with acute coronary syndrome (ACS) has not been well explored. We evaluated the impact of prior stroke/TIA on this specific patient population. We conducted an international multicenter study including 15 401 patients with ACS from the Bleeding Complications in a Multicenter Registry of Patients Discharged With Diagnosis of Acute Coronary Syndrome registry. They were divided into 2 groups: patients with and without prior stroke/TIA. The primary end point was death at 1-year follow-up. Prior stroke/TIA was associated with higher rate of 1-year death (8.7% vs 3.4%; P < .001). It was an independent predictor of 1-year death even after adjustment for confounding variables (odds ratio, 1.705; 95% confidence interval, 1.046-2.778; P = .032). Besides, patients with prior stroke/TIA had significantly increased 1-year reinfarction (5.6% vs 3.8%, P = .015), in-hospital bleeding (8.7% vs 5.8%, P < .001), and 1-year bleeding (5.2% vs 3.0%, P < .001). No difference of antithrombotic therapies or dual antiplatelet therapy (DAPT) types on outcomes was observed in patients with prior stroke/TIA. Prior stroke/TIA was associated with higher 1-year death for patients with ACS who underwent percutaneous coronary intervention. No benefits or harms were observed with different antithrombotic therapies or DAPT types in these patients.

Clinical whole exome sequencing in severe hypertriglyceridemia.

BACKGROUND: Little data exist regarding the clinical application of whole exome sequencing (WES) for the molecular diagnosis of severe hypertriglyceridemia (HTG). METHODS: WES was performed for 28 probands exhibiting severe HTG (≥1000 mg/dl) without any transient causes. We evaluated recessive and dominant inheritance models in known monogenic HTG genes, followed by disease-network gene prioritization and copy number variation (CNV) analyses to identify causative variants and a novel genetic mechanism for severe HTG. RESULTS: We identified possible causative variants for severe HTG, including three novel variants, in nine probands (32%). In the recessive inheritance model, we identified two homozygous subjects with lipoprotein lipase (LPL) deficiency and one subject harboring compound heterozygous variants in both LPL and APOA5 genes (hyperchylomicronemia). In the dominant inheritance model, we identified probands harboring deleterious heterozygous variants in LPL, glucokinase regulatory protein, and solute carrier family 25 member 40 genes, possibly associated with this extreme HTG phenotype. However, gene prioritization and CNV analyses did not validate the novel genes associated with severe HTG. CONCLUSIONS: In 28 probands with severe HTG, we identified potential causative variants within nine genes associated with rare Mendelian dyslipidemias. Clinical WES may be feasible for such extreme cases, potentially leading to appropriate therapies.

Impact of decreased ankle-brachial index on 30-day bleeding complications and long-term mortality in patients with acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND: Although concomitant peripheral artery disease in patients with acute coronary syndrome (ACS) has been considered as a high-risk subgroup with a greater incidence of bleeding after percutaneous coronary intervention (PCI), few data exist regarding the clinical utility of the ankle-brachial index (ABI) for predicting bleeding complications, which affects the subsequent outcome. METHODS: Eight hundred and twenty-four consecutive patients with ACS who underwent PCI and ABI examination were analyzed retrospectively. Decreased-ABI was defined as ABI <0.9. The primary outcome was bleeding complications within 30 days, which was defined according to the Bleeding Academic Research Consortium classification grade ≥3. The secondary endpoint was all-cause death during follow-up. RESULTS: Of the 824 patients with ACS, 137 (16.6%) exhibited decreased-ABI. The incidence of bleeding complications was significantly higher in patients with decreased-ABI, compared with the remaining patients (21.9% vs. 6.0%, p<0.001). In multivariate analysis, anemia [odds ratio (OR) 2.14], estimated glomerular filtration rate<60mL/min/1.73m2 (OR 2.14), femoral access (OR 3.31), use of an intra-aortic balloon pump (OR 3.16), and decreased-ABI (OR 2.58) were independent predictors of 30-day bleeding complications. Assigning 1 point for each variable, we developed a new bleeding risk score (range, 0-5). The area under the receiver-operating characteristic curve for the probability of 30-day bleeding for the new risk score was significantly superior than that of the traditional one (0.82 vs. 0.76, p<0.05). During the median 4-year follow-up, there were 98 incidents of all-cause death. Multivariate Cox-proportional hazard analysis revealed that decreased-ABI [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.15-3.13, p<0.05] and 30-day bleeding (HR 3.00, 95% CI 1.76-4.97, p<0.001) were associated with an increased risk of all-cause mortality. CONCLUSIONS: Assessment of ABI provides useful information for predicting 30-day bleeding complications and long-term mortality in patients with ACS after PCI.

Molecular and functional characterization of familial chylomicronemia syndrome.

BACKGROUND AND AIMS: Familial chylomicronemia syndrome is a rare autosomal recessive disorder leading to severe hypertriglyceridemia (HTG) due to mutations in lipoprotein lipase (LPL)-associated genes. Few data exist on the clinical features of the disorder or on comprehensive genetic approaches to uncover the causative genes and mutations. METHODS: Eight patients diagnosed with familial hyperchylomicronemia with recessive inheritance were included in this study (two males and six females; median age of onset 23.0 years; mean triglyceride level 3446 mg/dl). We evaluated their clinical features, including coronary artery disease using coronary computed tomography, and performed targeted next-generation sequencing on a panel comprising 4813 genes associated with known clinical phenotypes. After standard filtering for allele frequency <1% and in silico annotation prediction, we used three types of variant filtering to identify causative mutations: homozygous mutations in known familial hyperchylomicronemia-associated genes, homozygous mutations with high damaging scores in novel genes, and deleterious mutations within 37 genes known to be associated with HTG. RESULTS: A total of 1810 variants out of the 73,389 identified with 94.3% mean coverage (×20) were rare and nonsynonymous. Among these, our schema detected four pathogenic or likely pathogenic mutations in the LPL gene (p.Ala248LeufsTer4, p.Arg270Cys, p.Ala361Thr, and p.Val227Gly), including one novel mutation and a variant of uncertain significance. Patients harboring LPL gene mutations showed no severe atherosclerotic changes in the coronary arteries, but recurrent pancreatitis with long-term exposure to HTG was observed. CONCLUSIONS: These results demonstrate that LPL gene plays a major role in extreme HTG associated with hyperchylomicronemia, although the condition may not cause severe atherosclerosis.

Additive Prognostic Value of Carotid Plaque Score to Enhance the Age, Creatinine, and Ejection Fraction Score in Patients with Acute Coronary Syndrome.

AIM: To assess whether combining measurements obtained from carotid ultrasonography in addition to the age, creatinine, and ejection fraction (ACEF) score would improve the predictive ability of outcome in patients with acute coronary syndrome (ACS). METHODS: We examined 264 patients with ACS (194 men; mean age: 68±11 years) who underwent percutaneous coronary intervention. The carotid plaque score (cPS) and intima-media thickness (cIMT) were determined by carotid ultrasonography. The modified ACEF score was calculated using the following formula: (age/left ventricular ejection fraction) ＋1 point for every 10 mL/min reduction in creatinine clearance below 60 mL/min per 1.73 m2. The endpoint of this study was major adverse cardiovascular and cerebrovascular events (MACEs), defined as all-cause death, myocardial infarction, stoke, and target vessel revascularization. RESULTS: During the median 4-year follow-up, there were 121 incidents of MACEs. Multivariate Cox proportional hazard regression analysis revealed that cPS ≥9.8 (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.01-2.31) and ACEF score ≥1.20 (HR, 1.62; 95% CI, 1.11-2.39) were significantly associated with MACEs, whereas cIMT was not. When the new combined risk score was calculated by multiplying the cPS by the modified ACEF score, the freedom from MACEs at 5 years was 71% and 31% for the lower and higher scores, respectively (p＜0.001). The area under the receiver-operating characteristic curve for MACEs for the ACEF score, cPS, and combined risk score were 0.65, 0.66, and 0.71, respectively (p＜0.05). CONCLUSION: The cPS offers an incremental predictive value when combined to the simple ACEF score in ACS.

Gender-related differences in post-discharge bleeding among patients with acute coronary syndrome on dual antiplatelet therapy: A BleeMACS sub-study.

INTRODUCTION: Bleeding is an independent risk factor of mortality in patients with acute coronary syndromes (ACS). BleeMACS project focuses on long-term bleeding events after hospital discharge, thus we evaluated gender-related differences in post-discharge bleeding among patients with ACS. MATERIALS AND METHODS: We investigated 13,727 ACS patients treated with percutaneous coronary intervention and discharged on dual antiplatelet therapy (either with clopidogrel or prasugrel/ticagrelor). Endpoint was defined as intracranial bleeding or any other bleeding leading to hospitalization and/or red blood transfusion. RESULTS: Post-discharge bleeding was reported more frequently in females as compared with males (3.7% vs. 2.7%, log-rank P = 0.001). Females (n = 3165, 23%) were older compared to men (69.0 vs. 61.5 years, P < 0.001) and with more comorbidities. Hence, in multivariate analysis female sex was not identified as an independent risk factor of bleeding (HR 1.012, CI 0.805 to 1.274, P = 0.816). Administration of newer antiplatelet agents compared to clopidogrel was associated with over twofold greater bleeding rate in females (7.3% vs. 3.5%, log-rank P = 0.004), but not in males (2.6% vs. 2.7%, log-rank P = 0.887). Differences among females remained significant after propensity score matching (7.2% vs 2.4%, log-rank P = 0.020) and multivariate analysis confirmed that newer antiplatelet agents are independent risk factor for bleeding only in women (HR 2.775, CI 1.613 to 4.774, P < 0.001). CONCLUSIONS: Bleeding events occurred more frequently in women, but female sex itself was not independent risk factor. Administration of newer antiplatelet agents was identified as independent risk factor of bleeding after hospital discharge in female gender, but not in male patients.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy.

BACKGROUND: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. METHODS AND RESULTS: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral. CONCLUSION: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry.

BACKGROUND: A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. METHODS: We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). RESULTS: The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92-2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). CONCLUSION: Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.