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Background: Coronary artery perforation is one of the most feared and common complications of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods: To assess the usefulness of the recently developed PROGRESS-CTO (NCT02061436) perforation risk score in independent cohorts. Individual patient-level data pooled analysis of three registries was performed. Results: Of the 4566 patients who underwent CTO PCI at 25 centers, 196 (4.2%) had coronary artery perforation. Patients with perforations were older (69 ± 10 vs. 65 ± 10, p < 0.001), more likely to be women (19% vs. 13%, p = 0.009), more likely to have a history of prior coronary artery bypass graft (34% vs. 20%, p < 0.001), and unfavorable angiographic characteristics such as blunt stump (62% vs. 48%, p < 0.001), proximal cap ambiguity (52% vs. 34%, p < 0.001), and moderate-severe calcification (60% vs. 49%, p = 0.002). Technical success was lower in patients with perforations (73% vs. 88%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO perforation risk model was 0.76 (95% confidence interval [CI], 0.72−0.79), with good calibration (Hosmer-Lemeshow p = 0.97). We found that the CTO PCI perforation risk increased with higher PROGRESS-CTO perforation scores: 0.3% (score 0), 2.3% (score 1), 3.1% (score 2), 5.5% (score 3), 7.5% (score 4), 14.6% (score 5). Conclusion: Given the good discriminative performance, calibration, and the ease of calculation, the PROGRESS-CTO perforation score may facilitate assessment of the risk of perforation in patients undergoing CTO PCI.

Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUT-COMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW. Associations of baseline RDW with risk of MACE and death were analyzed in the placebo group in adjusted proportional hazards models. Interactions of RDW and treatment on the risk of MACE and death were evaluated. An increasing quartile of RDW was associated with characteristics that predicted risk of MACE and death including age, hypertension, diabetes, atherosclerotic conditions and events, revascularizations, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. After ad-justing for baseline characteristics associated with the risk of MACE or death, baseline RDW remained independently associated with the risk of MACE and death in the placebo group (hazard ratios [95% confidence intervals] 1.08 [1.02-1.15] and 1.13 [1.03-1.24] per 1% increase of RDW, respectively, both p < 0.001). There was no interaction of RDW and treatment on MACE or death, nor did alirocumab affect RDW. RDW was associated with an increased risk of MACE and death, independent of established risk factors.(c) 2022 National Lipid Association. Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.

This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22–2.12] and 1.46 [95%CI 1.09–1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15–6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02–4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59–10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.

Background The relationship between pulse pressure and prognosis in patients with chronic coronary syndrome (CCS) is contradictory. In the present study, we aimed to examine the relationship between intra-aortic pulse pressure (IAPP) and major adverse cardiovascular events (MACE) in patients with CCS undergoing percutaneous coronary intervention (PCI). Methods A total of 139 CCS patients who underwent elective PCI with regular one-year follow-up, were stratified into two subgroups according to IAPP. The primary outcomes included the occurrence of MACE, defined as cardiovascular death, acute myocardial infarction with ST-segment elevation (STEMI), acute myocardial infarction without ST-segment elevation (NSTEMI), target vessel revascularization (TVR), and stroke. Results The mean age of the patients was 57.6 +/- 10.4 years, 32% of whom were female. The mean IAPP, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 54.0 +/- 17.6 mmHg, 129.7 +/- 20 mmHg, and 75.8 +/- 11.8 mmHg, respectively. SBP, IAPP, and left ventricular ejection fraction (LVEF) were significantly higher in the high IAPP group (p < .001, p < .001, p = .001, respectively). The MACE rate was significantly higher in the low IAPP group than in the high IAPP group (30.4% vs. 8.6%, p = 0,001). The LVEF (OR = 0.93, CI:0.88-0.99, p = .025) and IAPP (OR = 0.89, CI:0.83-0.95, p = .001) were found to be independent predictors of MACE. The IAPP value of 39.5 mmHg was identified as an effective cutoff point for prediction of MACE-free survival rates (AUC:0.853, CI:0.768-0.937). Conclusion Invasively measured IAPP has prognostic information about cardiovascular outcomes in patients with CCS. The risk of MACE is significantly greater in CCS patients with low IAPP compared with those who have high IAPP values.

Background and aims: Studies on the association between growth-differentiation factor-15 (GDF-15) level and adverse outcomes have yielded conflicting results in patients with stable coronary artery disease (CAD). This meta-analysis aimed to evaluate the association of baseline GDF-15 level with adverse outcomes in stable CAD patients. Methods: Two authors independently searched PubMed and Embase databases from inception to May 31, 2021 for available studies that investigated the association of baseline GDF-15 level with all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events (MACEs) in stable CAD patients. Pooled multivariable adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for the highest vs. the lowest GDF-15 level. Results: Seven studies that involved 28,765 stable CAD patients were identified and analyzed. The meta-analysis showed that the highest GDF-15 level was associated with higher risk of MACEs (HR 1.42; 95% CI 1.29–1.57; p

Objective: To analyze the clinical characteristics of patients with type 2 diabetes mellitus (T2DM) with acute coronary syndrome (ACS), the global registry of acute coronary events (GRACE)score,the thrombolysis in myocardial infarction (TIMI) score and clinical prognosis. Method: The study was a retrospective one-center observational study, continuous inclusion of 600 ACS patients diagnosed by coronary angiography in our hospital from October 2018 to July 2019.Collect general clinical data, laboratory examination results, imaging data and interventional treatment data of all patients. Were divided into: T2DM with ACS group (group DA) and non-T2DM with ACS (group NDA) according to whether or not they were associated with T2DM. According to the GRACE、TIMI score, the two groups were divided into high risk group, middle risk group and low risk group.All patients underwent coronary angiography to calculate the number of vascular lesions and Gensini scores. Design questionnaire, after discharge to 2 groups of patients by telephone or outpatient follow-up average of 10 months, statistics of the occurrence of MACE events. Result: Among the 600 patients included in the study ,362 were male (60.3%) and 238 were female (39.7%) with mean age (64.7±10.3) years. The baseline data showed that the G、TG、UA、CR levels were higher in the DA group than in the NDA group; the proportion of men was lower than in the NDA group. The results of coronary angiography showed that the Gensini score of DA group was higher than that of NDA group, and the proportion of single lesion was lower than that of NDA group. The binary Logistic regression analysis suggested that age and CRP were independent risk factors for MACE events in patients with T2DM. GRACE risk stratification showed that the proportion of high risk group in DA group was significantly higher than that in NDA group, and there was no significant difference between low and middle risk group. TIMI risk stratification showed that the proportion of high risk group in DA group was significantly higher than that in NDA group, while the proportion of low and middle risk group was lower than that in NDA group. The ROC curve shows that the area (AUC) below the ROC curve that GRACE、TIMI score predicted the occurrence of MACE events in patients with T2DM and ACS was 0.707 and 0.586. Conclusion: Patients with T2DM and ACS had higher clinical risk stratification than without T2DM. GRACE score compared with the TIMI score had better predictive value for the occurrence of MACE events after discharge of T2DM with ACS patients.

Background: It has been demonstrated in previous studies that red blood cell distribution width (RDW) is correlated with the severity and prognosis of cardiovascular disease. The target of our study was to assess the relationship between RDW and the prognosis of ischemic cardiomyopathy (ICM) patients undergoing percutaneous coronary intervention (PCI). Methods: The study retrospectively enrolled 1986 ICM patients undergoing PCI. The patients were divided into three groups by RDW tertiles. The primary endpoint was major adverse cardiovascular events (MACE) and the secondary endpoints were each of the components of MACE (all-cause mortality, nonfatal myocardial infarction (MI) and any revascularization). Kaplan–Meier survival analyses were conducted to show the association between RDW and the incidence of adverse outcomes. The independent effect of RDW on adverse outcomes was determined by multivariate Cox proportional hazard regression analysis. In addition, the nonlinear relationship between RDW values and MACE was explored using restricted cubic spline (RCS) analysis. The relationship between RDW and MACE in different subgroups was determined using subgroup analysis. Results: As RDW tertiles increased, the incidences of MACE (Tertile 3 vs. Tertile 1: 42.6 vs. 23.7, p < 0.001), all-cause death (Tertile 3 vs. Tertile 1: 19.3 vs. 11.4, p < 0.001) and any revascularization (Tertile 3 vs. Tertile 1: 20.1 vs. 14.1, p < 0.001) increased significantly. The K–M curves showed that higher RDW tertiles were related to increased incidences of MACE (log-rank, p < 0.001), all-cause death (log-rank, p < 0.001) and any revascularization (log-rank, p < 0.001). After adjusting for confounding variables, RDW was proved to be independently associated with increased risks of MACE (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.75, 1.43–2.15; p for trend < 0.001), all-cause mortality (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.58, 1.17–2.13; p for trend < 0.001) and any revascularization (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.10, 1.54–2.88; p for trend < 0.001). In addition, the RCS analysis suggested nonlinear association between RDW values and MACE. The subgroup analysis revealed that elderly patients or patients with angiotensin receptor blockers (ARBs) had a higher risk of MACE with higher RDW. Patients with hypercholesterolemia or without anemia also had a higher risk of MACE. Conclusions: RDW was significantly related to the increased risk of MACE among ICM patients undergoing PCI.

Coronary artery ectasia (CAE) is defined as a dilatation of a coronary artery segment of at least 1.5 times the adjacent artery. CAE has been associated with worse clinical outcomes, and more complex interventional procedures. However, the exact risk for adverse events, especially in the context of myocardial infraction, remains unclear. The aim of the present thesis was to study whether patients with acute myocardial infarction (AMI) and evidence of CAE in coronary angiography are more prone to additional major adverse cardiovascular events (MACE), compared to patients without ectasia. A systematic review and meta-analysis of observational cohort studies was conducted. We systematically searched MEDLINE via PubMed, Scopus, the Cochrane Library (CENTRAL), ClinicalTrials.gov, and reference lists, to identify eligible studies. Baseline characteristics, comorbidities, angiographic data and rates of MACE and its individual components (including all-cause or cardiovascular mortality, repeat AMI, repeat revascularization, stroke, and heart failure) have been extracted. The quality of the included studies has been assessed and the results were synthesized as odds ratios (ORs) using random-effects models. Nine studies and 13,704 patients were included in the study. The definition of MACE varied significantly between the included studies, making meta-analysis on the composite outcome inappropriate, while the results about the risk of CAE for additional MACE were conflicting. CAE was not found to be predictive of higher odds of all-cause and cardiogenic mortality. The presence of ectasia was associated with higher odds of repeat AMI, compared with controls [OR:2.33, 95% CI:1.37 to 3.98]. The groups were comparable regarding the need for repeat revascularization, while the reports on stroke and heart failure were scarce. Results are conflicting on the effect of CAE on future MACE events in AMI. Patients with AMI and CAE have higher odds of repeat AMI compared to no-CAE patients. Mortality and repeat revascularization rates are comparable., Η εκτασία στεφανιαίων αρτηριών (ΕΣΑ) ορίζεται ως μια διάταση ενός τμήματος στεφανιαίας αρτηρίας, τουλάχιστον 1,5 φορές της προσκείμενης αρτηρίας. Η ΕΣΑ έχει συσχετιστεί με χειρότερα κλινικά αποτελέσματα και πιο περίπλοκες επεμβατικές διαδικασίες. Ωστόσο, ο ακριβής κίνδυνος για ανεπιθύμητα συμβάματα, ιδιαίτερα στα πλαίσια εμφράγματος του μυοκαρδίου, παραμένει ασαφής. Ο σκόπος της παρούσας διπλωματικής εργασίας ήταν να μελετηθεί το εάν οι ασθενείς με οξύ έμφραγμα του μυοκαρδίου (ΟΕΜ) και ευρήματα ΕΣΑ στην στεφανιαία αγγειογραφία είναι πιο επιρρεπείς σε επιπρόσθετα μείζονα ανεπιθύμητα καρδιαγγειακά συμβάματα (ΜΑΚΣ), σε σύγκριση με ασθενείς χωρίς εκτασία. Πραγματοποιήθηκε μια συστηματίκη ανασκόπηση και μετα-ανάλυση μελετών παρατήρησης. Ερευνήσαμε συστηματικά τις βάσεις MEDLINE μέσω του PubMed, την Scopus, την Cochrane Library (CENTRAL), το ClinicalTrials.gov, και λίστες βιβλιογραφικών αναφορών, για να εντοπίσουμε επιλέξιμες μελέτες. Τα βασικά χαρακτηριστικά, οι συννοσηρότητες, τα αγγειογραφικά δεδομένα και τα ποσοστά των ΜΑΚΣ και των μεμονωμένων στοιχείων τους (συμπεριλαμβανομένης της θνητότητας από οποιαδήποτε αιτία ή της καρδιαγγειακής θνητότητας, της επανάληψης του ΟΕΜ, της επαναληπτικής επαναγγείωσης, του εγκεφαλικού επεισοδίου και της καρδιακής ανεπάρκειας) σημειώθηκαν. Η ποιότητα των μελετών που συμπεριλήφθηκαν αξιολογήθηκε και τα αποτελέσματα συντέθηκαν ως αναλογίες πιθανοτήτων (ORs) χρησιμοποιώντας μοντέλα τυχαίων επιδράσεων. Στη μελέτη συμπεριλήφθηκαν εννέα μελέτες και 13.704 ασθενείς. Ο ορισμός των ΜΑΚΣ διέφερε σημαντικά μεταξύ των μελετών που συμπεριλήφθηκαν, καθιστώντας τη μετα-ανάλυση για το σύνθετο αποτέλεσμα ακατάλληλη, ενώ τα αποτελέσματα σχετικά με τον κίνδυνο της ΕΣΑ για επιπλέον ΜΑΚΣ ήταν αντικρουόμενα. Η ΕΣΑ δεν βρέθηκε να προδιαθέτει για μεγαλύτερη πιθανότητα θνητότητας από οποιαδήποτε αιτία ή καρδιαγγειακής θνητότητας. Η παρουσία ΕΣΑ συσχετίστηκε με μεγαλύτερη πιθανότητα επανάληπτικού ΟΕΜ, συκριτικά με την ομάδα ελέγχου [OR:2.33, 95% CI:1.37 με 3.98]. Οι ομάδες ήταν συγκρίσιμες σχετικά με την ανάγκη επαναληπτικής επαναγγείωσης, ενώ οι αναφορές σχετικά με το εγκεφαλικό επεισόδιο και την καρδιακή ανεπάρκεια ήταν σπάνιες. Τα αποτελέσματα έιναι αντικρουώμενα σχετικά με την επίδραση της ΕΣΑ στα μελλόντικα ΜΑΚΣ στα πλαίσια ΟΕΜ. Οι ασθενείς με ΟΕΜ και ΕΣΑ έχουν μεγαλύτερες πιθανότητες για επανάληψη του ΟΕΜ, συγκριτικά με ασθενείς χωρίς ΕΣΑ. Τα ποσοστά θνητότητας και επαναληπτικής επαναγγείωσης ήταν συγκρίσιμα.

BackgroundThe value of pooled cohort equations (PCE) as a predictor of major adverse cardiovascular events (MACE) is poorly established among symptomatic patients. Coronary artery calcium (CAC) assessment further improves risk prediction, but non-Western studies are lacking. This study aims to compare PCE and CAC scores within a symptomatic mixed Asian cohort, and to evaluate the incremental value of CAC in predicting MACE, as well as in subgroups based on statin use.MethodsConsecutive patients with stable chest pain who underwent cardiac computed tomography were recruited. Logistic regression was performed to determine the association between risk factors and MACE. Cohort and statin-use subgroup comparisons were done for PCE against Agatston score in predicting MACE.ResultsOf 501 patients included, mean (SD) age was 53.7 (10.8) years, mean follow-up period was 4.64 (0.66) years, 43.5% were female, 48.3% used statins, and 50.0% had no CAC. MI occurred in 8 subjects while 9 subjects underwent revascularization. In the general cohort, age, presence of CAC, and ln(Volume) (OR = 1.05, 7.95, and 1.44, respectively) as well as age and PCE score for the CAC = 0 subgroup (OR = 1.16 and 2.24, respectively), were significantly associated with MACE. None of the risk factors were significantly associated with MACE in the CAC > 0 subgroup. Overall, the PCE, Agatston, and their combination obtained an area under the receiver operating characteristic curve (AUC) of 0.501, 0.662, and 0.661, respectively. Separately, the AUC of PCE, Agatston, and their combination for statin non-users were 0.679, 0.753, and 0.734, while that for statin-users were 0.585, 0.615, and 0.631, respectively. Only the performance of PCE alone was statistically significant (p = 0.025) when compared between statin-users (0.507) and non-users (0.783).ConclusionIn a symptomatic mixed Asian cohort, age, presence of CAC, and ln(Volume) were independently associated with MACE for the overall subgroup, age and PCE score for the CAC = 0 subgroup, and no risk factor for the CAC > 0 subgroup. Whilst the PCE performance deteriorated in statin versus non-statin users, the Agatston score performed consistently in both groups.

Anemia is common in patients with chronic kidney disease and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in chronic kidney disease. Since then, new data from studies assessing established and emerging therapies for the treatment of anemia and iron deficiency have become available. Beginning in 2019, KDIGO planned 2 Controversies Conferences to review the new evidence and its potential impact on the management of anemia in clinical practice. Here, we report on the second of these conferences held virtually in December 2021, which focused on a new class of agents-the hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). This report provides a review of the consensus points and controversies from this second conference and highlights areas that warrant prioritization for future research.

Aim The prevalence of atherosclerotic cardiovascular (CV) disease has risen in Japan due to increasing metabolic risk factors, including dyslipidemia. A positive linear correlation between low-density lipoprotein cholesterol (LDL-C) levels, incidence of CV events, and preventive effects of lipid-lowering therapy (LLT) is well established; however, data in Japan are limited. This analysis evaluated current lipid management practices and risk of recurrent CV events in Japanese post-acute coronary syndrome (ACS) patients. Methods EXPLORE-J is a multicenter, 2-year observational study of hospitalized ACS patients in Japan. Results At 2-year follow-up (n=1944, mean age 66 years, 80.3% male), the cumulative incidence of major adverse cardiovascular events (MACE; death associated with myocardial infarction/cerebrovascular accident [CVA] and other CV death, non-fatal ACS, and non-fatal CVA requiring hospitalization during the observation period) was 6.2%; respective incidences of CV death, non-fatal ACS, and CVA were 0.7%, 4.5%, and 1.7%. Statin, intensive statin, and ezetimibe were prescribed for 93.6%, 8.2%, and 3.9% at visit (V)1 (Day[D]1＋14), and 92.3%, 10.5%, and 11.6% of patients at V5 (D730±30 days), respectively. Mean LDL-C was reduced from first post-ACS measurement (121.3 mg/dL) to V5 (79.8 mg/dL). A limited number of patients achieved LDL-C ＜70 mg/dL from V1-V5 (14.4%-34.6%); those with a greater LDL-C reduction by V1 had a lower probability of MACE, indicating the benefits of early LDL-C reduction post ACS. Conclusions Guideline-recommended LDL-C target achievement post ACS in Japan is suboptimal, suggesting the need for LLT intensification. Additional analyses by risk stratification of the study population and the benefits of lipid management are planned.

Xiaoxiao Zhao,1,&ast; Li Song,1,&ast; Ying Wang,1,&ast; Jiannan Li,1 Jinying Zhou,1 Runzhen Chen,1 Chen Liu,1 Peng Zhou,1 Zhaoxue Sheng,1 Yi Chen,1 Hanjun Zhao,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing YanFuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of ChinaTel +86-13701339287Email hbyanfuwai2018@163.comHanjun ZhaoDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of ChinaTel +86-15210020808Email 15210020808@163.comBackground and Aim: The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention.Methods: A total of 434 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure.Outcomes: During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture.Conclusion and Relevance: This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.Keywords: pentraxin-3, PCSK9, plaque morphology characteristics, optical coherence tomography, major adverse cardiovascular events, ST-segment elevation myocardial infarction

Background and Aim The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. Methods A total of 434 patients with STEMI aged ≥18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure. Outcomes During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture. Conclusion and Relevance This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.

Background Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). Methods This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. Results AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084–1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205–1.474, P P = 0.016; Model 3: HR = 1.194, 95% CI 1.049–1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077–1.303, P P P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255–1.669, P P = 0.015; Model 3: HR = 1.284, 95% CI 1.071–1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. Conclusions This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. Trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5‐year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. Methods A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five‐year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One‐year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. Results There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5‐year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1‐year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03–6.26) per 100 person‐years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45–15.20) per 100 person‐years. Conclusions This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.

Background The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes. Methods From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events. Results A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08–2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23–3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17–2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17–5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08–3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29–3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03–5.71, P = 0.044) were at a higher risk for MACE by diabetes. Conclusion OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk.

We conducted this study to investigate the long-term outcomes of sulfonylurea (SU) use in patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). We used propensity-score matching to identify 6008 pairs of SU users and nonusers from Taiwan’s National Health Insurance Research Database from 1 January 2000 to 31 December 2017. Cox proportional hazard models were used to compare the risks of mortality, cardiovascular events, non-invasive positive pressure ventilation, invasive mechanical ventilation, bacterial pneumonia, lung cancer, and hypoglycemia between SU users and nonusers. In the matched cohorts, the mean follow-up time for SU users and nonusers was 6.57 and 5.48 years, respectively. Compared with nonusers, SU users showed significantly lower risks of mortality [aHR 0.53(0.48–0.58)], cardiovascular events [aHR 0.88(0.81–0.96)], non-invasive positive pressure ventilation [aHR 0.74(0.6–0.92)], invasive mechanical ventilation [aHR 0.57(0.5–0.66)], and bacterial pneumonia [aHR 0.78(0.7–0.87)]. A longer cumulative duration of SU use was associated with a lower risk of these outcomes. This nationwide cohort study demonstrated that SU use was associated with significantly lower risks of cardiovascular events, ventilation use, bacterial pneumonia, and mortality in patients with COPD and T2D. SU may be a suitable option for diabetes management in these patients.

Background: Diabetic retinopathy (DR) and preclinical atherosclerosis are associated with higher cardiovascular risk. However, no studies have investigated the predictive role of DR and preclinical atherosclerosis jointly on cardiovascular events in subjects with type 2 diabetes (T2D). We aimed to assess the contribution of DR and subclinical atherosclerosis on the risk of adverse cardiovascular events in subjects with T2D without previous cardiovascular disease (CVD). Methods: We included two prospective cohorts of subjects with T2D from the same geographical area. Assessment of subclinical atherosclerosis was performed by carotid ultrasound. An ophthalmologist classified DR according to standard criteria. Cardiovascular outcomes considered for analysis were the following: ischemic heart disease, stroke, heart failure, peripheral artery disease, revascularization procedures, and cardiovascular mortality. Bivariable and multivariable predictive models were performed. Results: From a total of 374 subjects with T2D 44 developed cardiovascular events during the 7.1 years of follow-up. Diabetes duration, total cholesterol, and glycated hemoglobin (HbA1c) at baseline were higher in subjects who developed cardiovascular outcomes (p < 0.001, p = 0.026, and p = 0.040, respectively). Compared with subjects without events, those developing cardiovascular events had higher prevalence of retinopathy (65.9% vs. 38.8%, p = 0.001; respectively) and more than mild retinopathy (43.2% vs. 31.8%, p = 0.002; respectively). Furthermore, all-cause mortality was higher in subjects with MACE than those without events (13.6% vs. 3.3%, p = 0.009; respectively). The multivariable analyses showed that HbA1c and the presence of DR at baseline were predictive of cardiovascular outcomes (p = 0.045 and p = 0.023, respectively). However, the burden of subclinical atherosclerosis was not (p = 0.783 and p = 0.071, respectively). Conclusion: DR is a strong predictor of cardiovascular events in T2D individuals at primary CVD prevention, even after accounting for the presence of preclinical carotid atherosclerosis. These results may help to individualize CVD prevention strategies in T2D. This study was supported by grants PS09/01035 and PI11/01723 from the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness and FEDER, Spain. CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) and CIBEROBN were initiatives of Instituto de Salud Carlos III, Spain. MR-L held a predoctoral fellowship from the Departament de Salut, SLT017/20/000107. JJ was recipient of a Miguel Servet Type 2 contract (CPII18/00004; ISCIII). JJ was member of Red de Investigación en “Enfermedades Metabólicas y Cáncer” (RED2018-102799-T), Ministerio de Economía y Competitividad (MINECO), Madrid, Spain. Institut de Recerca del Hospital de la Santa Creu i Sant Pau and Biomedical Research Institute’s Dr. Pifarré Foundation from Lleida (IRBLleida) were accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA).

Background: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. Methods: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. Results: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66–9.67) and MICA score aOR = 1.21 (1.03–1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08–1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. Conclusion: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND. info:eu-repo/semantics/publishedVersion

Aleksandra G&aogon;secka,1 Piotr Szwed,1 Karolina Jasi&nacute;ska,1 Oliwia Fidali,1 Aleksandra K&lstrok;&eogon;bukowska,1 Ceren Eyileten,2 Marek Postula,2 &Lstrok;ukasz Szarpak,3,4 Tomasz Mazurek,1 Grzegorz Opolski,1 Krzysztof J Filipiak,1 Marcin Ufnal5 1 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, 02-097, Poland; 2Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-097, Poland; 3Bialystok Oncology Center, Bialystok, 15-027, Poland; 4Maria Sklodowska-Curie Medical Academy in Warsaw, Warsaw, 03-411, Poland; 5Department of Experimental Physiology and Pathophysiology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-106, PolandCorrespondence: Aleksandra G&aogon;secka 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, Warsaw, 02-097, PolandTel +48 22 599 19 51Email aleksandra.gasecka@wum.edu.plPurpose: Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Damage to the endothelium is the earliest event in atherothrombosis, including AMI. Nitric oxide (NO), an endothelium-derived compound, protects the vasculature from damage. This study evaluated whether an association exists between plasma concentration of endogenous NO-related pathway metabolites linked to AMI and major adverse cardiovascular events (MACE) after AMI.Methods: We compared plasma concentrations of NO-related pathway metabolites in patients after AMI (n=60) and healthy controls (n=27) and investigated the prognostic value of these metabolites for post-AMI MACE development over a median of 3.5-years. In search of biomarkers, we compared plasma concentrations of dimethylarginines (ADMA, SDMA), citrulline, arginine and ornithine using ultra performance liquid chromatograph coupled with a mass spectrometer.Results: Patients after AMI had higher concentrations of dimethylarginines, compared to controls (p=0.0068, p< 0.0001, respectively). Conversely, the concentration of citrulline was lower in the AMI group (p=0.0006). The concentration of SDMA was higher in patients who developed MACE than in those who did not (p=0.015). SDMA was the only independent predictor of MACE in multivariate analysis (p=0.023). There was an intermediate, negative correlation between plasma SDMA level and platelet reactivity (r=− 0.33, p=0.02).Conclusion: Plasma concentration of dimethylarginines differs between patients with AMI and healthy volunteers. The study’s novel finding is that SDMA is an independent predictor of MACE during a 3.5 year follow-up period after AMI.Keywords: nitric oxide, L-arginine, acute myocardial infarction, major adverse cardiovascular events, prognosis

Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

The association between fragmented QRS (fQRS) and autonomic nervous dysfunction, and major adverse cardiovascular events (MACE) is not fully clear in patients with acute myocardial infarction (AMI). This study aimed to observe whether combined assessment with fQRS and cardiac autonomic nervous function could enhance the predicting efficacy on outcome in AMI patients. A total of 153 consecutive hospitalized AMI patients were included in this retrospective study. Patients were divided into non-fQRS (nfQRS) group and fQRS group according to 12-lead electrocardiogram, into sHRV [severely depressed heart rate variability (HRV): standard deviation of NN intervals (SDNN) p p p = 0.003). The predicting sensitivity and specificity on MACE were 81.4 and 58.2% by sHRV, 69.8 and 69.1% by fQRS in these AMI patients. The specificity (81.8%) was the highest with the combination of sHRV and fQRS. Adding sHRV and fQRS to clinical data offered incremental prognostic value. Present results indicate that fQRS is closely related to sHRV, suggesting significant impairment of sympathetic nerve function in AMI patients with fQRS. Combined assessment with fQRS and sHRV enhances the predicting efficacy on outcome in AMI patients.

Background:. It remains unclear whether the outcomes of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) during off-hours are as favorable as those treated during on-hours, especially those with a first medical contact-to-device (FMC-to-device) time within 90 min. We aimed to determine whether off-hours admission impacted late outcomes in patients undergoing PPCI and with an FMC-to-device time ≤90 min. Methods:. This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time ≤90 min from 19 chest pain centers in Beijing from January 2018 to December 2018. Patients were divided into on-hours group and off-hours group based on their arrival time. Baseline characteristics, clinical data, and key time intervals during treatment were collected from the Quality Control & Improvement Center of Cardiovascular Intervention of Beijing by the “Heart and Brain Green Channel” app. Results:. Overall, the median age of the patients was 58.8 years and 19.9% (133/670) were female. Of these, 296 (44.2%) patients underwent PPCI during on-hours and 374 (55.8%) patients underwent PPCI during off-hours. Compared with the on-hours group, the off-hours group had a longer FMC-to-device time and fewer patients with FMC-to-device time ≤60 min (P 0.05). According to the Cox regression analyses, off-hours admission was not a predictor of 2-year MACEs (P = 0.788). Similarly, the Kaplan-Meier curves showed that the risks of a MACE, all-cause death, reinfarction, and target vessel revascularization were not significantly different between the two groups (P > 0.05). Conclusions:. This real-world, multicenter retrospective study demonstrated that for STEMI patients who underwent PPCI within 90 min, off-hours admission was safe, with no difference in the risk of 2-year MACEs compared with those with on-hours admission.

Background: The ambulatory arterial stiffness index (AASI) obtained during ambulatory blood pressure monitoring (ABPM) has been cited as an independent predictor of major adverse cardiovascular events (MACEs) including cardiovascular death, stroke and worsening chronic kidney disease (CKD) among mixed-sex adult populations. This study aimed to determine the relationship between AASI and MACE and its predictive precision in women. Methods: This work follows the guidelines of the STROBE initiative for cohort studies. This was a retrospective single-center observational study of adult women (aged 18 – 75 years), who underwent 24-h ABPM for the diagnosis of hypertension or its control. The primary endpoint was a composite MACE of cardiovascular death, acute limb ischemia, stroke, acute coronary syndrome (ACS), or progression to stage V CKD. Results: A total of 219 women aged 57.4 ± 13.3 years were followed up for a median (interquartile range (IQR)) of 25.5 (18.3 – 31.3) months. Overall, 16 (7.3%) patients suffered one or more MACE events. AASI was significantly higher in patients with known coronary artery disease (CAD), diabetes mellitus, peripheral vascular disease (PVD), heart failure, previous stroke, or transient ischemic attack (TIA). AASI was a significant predictor of MACE (area under the curve: 0.78; P < 0.001) with an optimal cut-off of ≥ 0.56. On Kaplan-Meier analysis AASI ≥ 0.56 was significantly associated with MACE (log-rank test, P < 0.001). The only independent predictors of MACE on Cox proportional hazard analysis were diabetes mellitus, low high-density lipoprotein (HDL) levels, cumulative AASI values, or AASI ≥ 0.56. Conclusions: An AASI of ≥ 0.56 is an independent predictor of MACE in women. A further validation study in a larger cohort of women is recommended.

Aims Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). Methods and results We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61–0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64–0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34–0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66–0.90; P Conclusion Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Jemi Galani,1 Hillary Mulder,2 Frank W Rockhold,2 E Hope Weissler,2,3 Iris Baumgartner,4 Jeffrey S Berger,5 Juuso I Blomster,6 F Gerry R Fowkes,7 William R Hiatt,8,9 Brian G Katona,10 Lars Norgren,11 Kenneth W Mahaffey,12 Jennifer K Quint,13 Manesh R Patel,1,2 W Schuyler Jones1,2 1Department of Medicine, Duke University Medical Center, Durham, NC, USA; 2Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA; 3Department of Surgery, Division of Vascular Surgery, Duke University Health System, Durham, NC, USA; 4Department of Medicine, Swiss Cardiovascular Center, University of Bern, Bern, Switzerland; 5Departments of Medicine and Surgery, New York University School of Medicine, New York, NY, USA; 6University of Turku, Turku, Finland; 7Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK; 8Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA; 9CPC Clinical Research, Aurora, CO, USA; 10AstraZeneca, Gaithersburg, MD, USA; 11Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 12Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA; 13Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: W Schuyler JonesDuke University Medical Center, Box 3330, Durham, NC, 27710, USATel +1 919-668-8917Fax +1 919-668-7026Email schuyler.jones@duke.eduBackground: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD.Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model.Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p< 0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p< 0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11– 1.52; p< 0.001; MI: aHR 1.45, 95% CI 1.18– 1.77; p< 0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12– 3.63; p< 0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p< 0.001; aHR 1.34, 95% CI 1.22– 1.47; p< 0.001).Conclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD.Registration: ClinicalTrials.gov: NCT01732822.Keywords: peripheral artery disease, chronic obstructive pulmonary disease, major adverse cardiovascular events

Objectives: International cardiovascular guidelines recommend prescribing a combination of five evidence-based medications (EBM) for acute coronary syndrome (ACS) patients post-revascularization. This study aims to assess the prevalence and impact of prescribing the full (five medications) versus partial (four medications or fewer) EBM combination on major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS post-revascularization. Methods: Data from patients with ACS who had revascularization between January 2016 and September 2021 were collected retrospectively. Patients were then followed up until March 2022 for MACCE. Results: The full EBM combination was prescribed to 70% of the patients. However, after taking into account the presence of contraindications and clinical factors, the actual adherence to the guidelines was 95%. Patients who received the full EBM combination were younger (58 versus 62 years; p = 0.0 and 3) and had lower rates of chronic kidney disease (11% versus 41%; p < 0.001) and heart failure (9% versus 20%; p = 0.012) when compared to patients who received the partial EBM. Compared to the partial EBM group, the full EBM group was associated with lower MACCE rates (54% versus 37%, p = 0.012). After employing the propensity score technique utilizing the 1:1 nearest neighbor matching method without replacement, the univariate findings were further re-affirmed with those on full EBMs (compared to those on partial EBMs) associated with a significant reduction in the MACCE rate (average treatment effect of −25%; 95% confidence interval: −10–−40%; p = 0.001). Conclusions: The full EBM utilization was significantly high in our setting and in line with international guidelines. The full EBM combination was predominantly prescribed in younger and less comorbid patients and was associated with lower MACCE rates. The findings were further reaffirmed by the propensity score matching method.

Background: The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs. Results: Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants’ mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91–0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87–1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes. Conclusions: The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.

Aktaş, Halil ( Aksaray, Yazar ), Objective: Several studies have investigated different cardiac biomarkers as predictors of the prognosis after percutaneous coronary interventions (PCI) in patients with chronic ischemic heart disease; nevertheless, the results of these studies are conflicting. High sensitive troponin T (Hs-TnT) measurement is a novel and sensitive method. The aim of this study was to investigate if Hs-TnT levels are a predictor of major adverse cardiovascular events (MACE) in the first year after a successful elective PCI in patients with stable angina pectoris (SAP). Material and methods: 100 patients who presented with SAP and underwent successfully elective PCI were included in the study. Patients with elevated troponin I levels (>0.1 ng/mL) before the procedure excluded from the study. Hs-TnT levels were measured before the procedure and at 3-4 hours (h) (early period) and 12-24 hours (late period) after the procedure and Hs-TnT level >14 pg/mL was considered positive. The incidence of MACE during the first year was recorded. Results: Hs-TnT levels were positive in 36% of the patients in the early period and in 54% of the patients in the late period. The incidence rate of MACE for the first year was significantly higher in the patients with positive Hs-TnT levels in the early period but not the late period (36.1% vs. 15.6%; p = 0.026) and logistic regression analysis yielded an odds ratio of 3.36. Conclusion: Hs-TnT levels measured 3-4 h after a successful elective PCI in patients with SAP can predict the incidence of MACE within the first year. Nonetheless, these results must be corroborated by other larger studies.

Background Fragmented QRS (fQRS) is a marker of local myocardial scar. This study aimed to analyze the relationship between fQRS and coronary collateral circulation (CCC) and evaluate the predictive value of fQRS for long‐term clinical outcomes among patients with chronic total occlusion (CTO) and prior myocardial infarction (MI) who underwent percutaneous coronary intervention (PCI). Methods A total of 862 patients with a definite history of MI who had one CTO coronary artery and underwent PCI between 2013 and 2018 were continuously analyzed. Patients were divided into group A (no Q wave and fQRS, n = 206), group B (fQRS, n = 265), group C (Q wave, n = 391). All patients were followed up for 2 years. Results The incidence rate of major adverse cardiovascular events (MACE) in group B was significantly lower than in group C (group B vs. C: 7.2% vs. 11.3%, P = 0.043). The percentage of good CCC was 94.2%, 88.3%, and 82.9% in group A, B, and C (p

The relationship between small dense low‐density lipoprotein cholesterol (sdLDL‐C) and different cardiovascular events has been observed in several large community studies, and the results have been controversial. However, there is currently no cross‐sectional or longitudinal follow‐up study on sdLDL‐C in the Chinese hypertension population. We analyzed the association of plasma sdLDL‐C levels with major adverse cardiovascular events in 1325 subjects from a longitudinal follow‐up community‐based population in Beijing, China. During the follow‐up period, a total of 191 subjects had MACEs. Cox regression analysis showed that sdLDL‐C is a major risk factor for MACEs independent of sex, age, BMI, hypertension, diabetes, smoking, SBP, DBP, FBG, eGFR in the general community population (1.013 (1.001 −1.025, P

Context: Left ventricular ejection fraction (LVEF) recovery is an important treatment goal for patients with heart failure (HF) and reduced EF (HFrEF); however, the applicability of the left atrial volume index (LAVI) in predicting long-term LVEF recovery in HFrEF remains unknown. Aim: We aimed to assess the predictive value of the LAVI in predicting long-term LVEF recovery in patients hospitalized with HFrEF. Settings and Design: This was a retrospective cohort study. Materials and Methods: We analyzed 70 decompensated patients with HF, hospitalized between 2013 and 2014, with an LVEF 3 years postdischarge. Predictive LAVI values used to predict long-term LVEF improvement were determined. Statistical Analysis: The survival rate was determined using Kaplan–Meier analysis. In receiver operating characteristic curve (ROC) analysis, the area under the curve (AUC) and optimal cutoff values were obtained from several echocardiographic parameters. Univariate and multivariate logistic regression analyses identified predictors of LVEF improvement. Results: Twenty-seven (39%) patients had recovered LVEFs. During a median follow-up period of 76 (60–80) months, the survival rate was significantly higher in the recovered group (log-rank test, P = 0.001). ROC analysis showed that LAVI's predictive performance in long-term LVEF improvement (AUC 0.78, 95% confidence interval [CI] 0.66–0.87) was optimal at a cutoff of 35 g/m2. LAVI

Objective: To compare the value of HEART and TIMI scores in predicting major adverse cardiovascular events (MACEs) of patients with chest pain in the emergency department at a tertiary care hospital in Ahmedabad, a city in western India. Methods: A prospective study was conducted on chest pain patients from January to December 2019. All adult patients with non-traumatic chest pain presenting to the emergency department were included, and their HEART and TIMI scores were evaluated. The patients were followed up within 4 weeks for monitoring any major adverse cardiac events or death. The receiver-operating characteristics (ROC) curve was used to determine the value of HEART and TIMI scores in predicting MACEs. Besides, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the two scores were assessed and compared. Results: A total of 350 patients were evaluated [mean age (55.03±16.6) years, 56.6% of males]. HEART score had the highest predictive value of MACEs with an area under the curve (AUC) of 0.98, followed by the TIMI score with an AUC of 0.92. HEART score had the highest specificity of 98.0% (95% CI: 96.4%-99.6%), the sensitivity of 75.0% (95% CI: 70.7%-79.3%), and PPV of 97.0% (95% CI: 94.1%-99.9%) and NPV of 82.5% (95% CI: 74.6%-90.4%) for low-risk patients. TIMI score had a specificity of 95.0% (95% CI: 92.4%-97.6%), sensitivity of 75.0% (95% CI: 69.4%-80.6%), PPV of 92.3% (95% CI: 88.1%-96.5%) and NPV of 82.3% (95% CI: 73.8%-90.8%) for low-risk patients. Conclusions: HEART score is an easier and more practical triage instrument to identify chest pain patients with low-risk for MACEs compared to TIMI score. Patients with high HEART scores have a higher risk of MACEs and require early therapeutic intervention and aggressive management.

Background Hypertriglyceridemia (HTG) is considered an independent risk factor for major adverse cardiovascular events (MACE). Methods This study analyzed the effects of various agents on MACE risk reduction in HTG (serum triglyceride ≥ 150 mg/dl) populations by performing a network meta-analysis. We performed a frequentist network meta-analysis to conduct direct and indirect comparisons of interventions. PubMed, EMBASE, and the Cochrane library were searched for trials until Jul 6, 2020. Randomized controlled trials that reported MACE associated with agents in entire HTG populations or in subgroups were included. The primary outcome was MACE. Results Of the 2005 articles screened, 21 trials including 56,471 patients were included in the analysis. The network meta-analysis results for MACE risk based on frequency data showed that eicosapentaenoic acid (EPA) (OR: 1.32; 95% CI 1.19–1.46), gemfibrozil (OR: 1.53; 95% CI 1.20–1.95), niacin plus clofibrate (OR: 2.00; 95% CI 1.23–3.25), pravastatin (OR: 1.32; 95% CI 1.15–1.52), simvastatin (OR: 2.38; 95% CI 1.55–3.66), and atorvastatin (OR: 0.55; 95% CI 0.37–0.82) significantly reduced the risk of MACE compared to the control conditions. In the subgroup analysis of HTG patients with triglycerides ≥ 200 mg/dL, bezafibrate (OR: 0.56; 95% CI 0.33–0.94), EPA (OR: 0.72; 95% CI 0.62–0.82), and pravastatin (OR: 1.33; 95% CI 1.01–1.75) significantly reduced the MACE risk. Conclusions Simvastatin had a clear advantage in reducing the risk of MACE in the entire HTG population analyzed in this meta-analysis. EPA, but not omega-3 fatty acid, was considered an effective HTG intervention. Among fibrates, gemfibrozil was most effective, though bezafibrate may significantly reduce the risk of MACE in populations with triglyceride levels of 200–300 mg/dL. Trial registration retrospectively registered in PROSPERO (CRD42020213705).

Susan Labib, Hussein Heshmat Kassem, Hossam Kandil Department of Cardiology, Cairo University, Cairo, EgyptCorrespondence: Susan LabibDepartment of Cardiology Cairo University, Kasr Alainy University Hospital, 23, Second Floor, Manial, Cairo, EgyptTel +201006928590Email dr.suzanlabib@gmail.comBackground: Peri-procedural blood-pressure (BP) changes were investigated and correlated to Major adverse cardiovascular events (MACE) as predictor of outcome for patients undergoing percutaneous coronary intervention (PCI); whether acute coronary syndrome (Unstable angina, or MI; STEMI or NSTEMI) or scheduled for elective PCI.Methods: Resting BP in the 204 recruited patients undergoing PCI throughout 2018 was measured thrice – in the ward before transferring to the cardiac catheterization lab (cath lab), in the cath lab, and after transfer to the recovery room. Patients were categorized based on their systolic and diastolic BP peri-procedural difference as systolic (SBP): with a large difference (> 20 mmHg, n=47), with a small difference (≤ 20 mmHg, n=157) (shock patients excluded); diastolic (DBP): with a large difference (> 10 mmHg, n=65), and with a small difference (≤ 10 mmHg, n=139). The primary end-points were MACE including all-cause mortality, non-fatal myocardial infarction, and stroke during the hospital stay. The Mann–Whitney U and Chi-square tests were used to analyze the data accordingly (p< 0.005).Results: Within the category of MACE, cardiac mortality was the only adverse cardiac event encountered in the study sample. Cardiac mortality was significantly higher in both the large SBP-difference group versus the other group (10.6% vs 0.6%, p=0.003) and the large DBP-difference group versus the small-difference group (7.7% vs 0.7%, p=0.013).Conclusion: Peri-procedural systolic and diastolic BP differences, greater than 20 mmHg and 10 mmHg, respectively, correlated with MACE in all patients undergoing PCI.Keywords: percutaneous coronary intervention, major adverse cardiovascular events, peri-procedural BP changes

Susan Labib, Hussein Heshmat Kassem, Hossam Kandil Department of Cardiology, Cairo University, Cairo, EgyptCorrespondence: Susan LabibDepartment of Cardiology Cairo University, Kasr Alainy University Hospital, 23, Second Floor, Manial, Cairo, EgyptTel +201006928590Email dr.suzanlabib@gmail.comBackground: Peri-procedural blood-pressure (BP) changes were investigated and correlated to Major adverse cardiovascular events (MACE) as predictor of outcome for patients undergoing percutaneous coronary intervention (PCI); whether acute coronary syndrome (Unstable angina, or MI; STEMI or NSTEMI) or scheduled for elective PCI.Methods: Resting BP in the 204 recruited patients undergoing PCI throughout 2018 was measured thrice – in the ward before transferring to the cardiac catheterization lab (cath lab), in the cath lab, and after transfer to the recovery room. Patients were categorized based on their systolic and diastolic BP peri-procedural difference as systolic (SBP): with a large difference (> 20 mmHg, n=47), with a small difference (≤ 20 mmHg, n=157) (shock patients excluded); diastolic (DBP): with a large difference (> 10 mmHg, n=65), and with a small difference (≤ 10 mmHg, n=139). The primary end-points were MACE including all-cause mortality, non-fatal myocardial infarction, and stroke during the hospital stay. The Mann–Whitney U and Chi-square tests were used to analyze the data accordingly (p< 0.005).Results: Within the category of MACE, cardiac mortality was the only adverse cardiac event encountered in the study sample. Cardiac mortality was significantly higher in both the large SBP-difference group versus the other group (10.6% vs 0.6%, p=0.003) and the large DBP-difference group versus the small-difference group (7.7% vs 0.7%, p=0.013).Conclusion: Peri-procedural systolic and diastolic BP differences, greater than 20 mmHg and 10 mmHg, respectively, correlated with MACE in all patients undergoing PCI.Keywords: percutaneous coronary intervention, major adverse cardiovascular events, peri-procedural BP changes

AimsThe safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients.Methods and resultsIn this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%).ConclusionWe report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients.

Introduction: This study aimed to estimate risks of cardiovascular and cerebrovascular events in patients treated with lisdexamfetamine dimesylate (LDX) compared with patients previously treated with other attention-deficit/hyperactivity disorder (ADHD) medications (amphetamine, dexamphetamine, methylphenidate or atomoxetine). Methods: This population-based cohort study used data from Danish and Swedish medical and administrative national registers. The LDX cohort included adult patients initiating LDX with at least 12 months’ data preceding first LDX dispensing (index date). A random sample of patients treated with at least one non-LDX ADHD medication in the 6–24 months (but not less than 6 months) before index date (previous-users cohort) were matched to LDX users on age, sex, region and calendar year. The primary outcome, a composite of major adverse cardiovascular and cerebrovascular events (MACE), included first hospitalisation for acute myocardial infarction or stroke and out-of-hospital coronary heart disease or cerebrovascular disease death. Incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) of MACE were estimated using Poisson regression. Results: From Denmark/Sweden, 5516/40,163 LDX users and 27,494/200,389 previous users were included. In Denmark, IRs of MACE/1000 person-years (95% CI) were similar for LDX (1.63 [0.85–3.14]) and previous users (1.61 [1.28–2.01]). In Sweden, IRs (95% CI) were 1.40 (1.09–1.79) in LDX users and 1.17 (1.00–1.38) in previous users. Adjusted MACE IRRs (95% CI) for LDX versus previous use were 1.01 (0.48–2.13) in Denmark, 1.13 (0.75–1.71) in Sweden, and 1.10 (0.77–1.58) in the pooled analysis. Conclusion: Our findings suggest little to no increased risk of cardiovascular and cerebrovascular events in patients treated with LDX compared with patients previously treated with other ADHD medications.

Objective The risk of major adverse cardiovascular events (MACE) for older emergency department (ED) patients presenting with non-cardiac medical complaints is unknown. To apply preventive measures timely, early identification of high-risk patients is incredibly important. We aimed at investigating the incidence of MACE within one year after their ED visit and the predictive value of high-sensitivity cardiac troponin T (hs-cTnT) and N‑terminal pro-B-type natriuretic peptide (NT-proBNP) for subsequent MACE. Methods This is a substudy of a Dutch prospective cohort study (RISE UP study) in older (≥ 65 years) medical ED patients who presented with non-cardiac complaints. Biomarkers were measured upon ED arrival. Cox-regression analysis was used to determine the predictive value of the biomarkers, when corrected for other possible predictors of MACE, and area under the curves (AUCs) were calculated. Results Of 431 patients with a median age of 79 years, 86 (20.0%) developed MACE within 1 year. Both hs-cTnT and NT-proBNP were predictive of MACE with an AUC of 0.74 (95% CI 0.68–0.80) for both, and a hazard ratio (HR) of 2.00 (95% CI 1.68–2.39) and 1.82 (95% CI 1.57–2.11) respectively. Multivariate analysis correcting for other possible predictors of MACE revealed NT-proBNP as an independent predictor of MACE. Conclusion Older medical ED patients are at high risk of subsequent MACE within 1 year after their ED visit. While both hs-cTnT and NT-proBNP are predictive, only NT-proBNP is an independent predictor of MACE. It is likely that early identification of those at risk offers a window of opportunity for prevention.

Background Inflammation is involved in the pathogenesis and progression of coronary artery diseases (CADs), including acute coronary syndrome. The neutrophil-to-lymphocyte ratio (NLR) has been identified as a novel marker of the pro-inflammatory state. We aimed to evaluate the predictive efficacy of the NLR for the prognosis of patients with new-onset ACS. Methods We retrospectively included consecutive patients with new-onset ACS treated with emergency coronary angiography. NLR was measured at baseline and analyzed by tertiles. The severity of coronary lesions was evaluated by the Gensini score. Correlations of NLR with the severity of CAD and the incidence of major adverse cardiovascular diseases (MACEs) during follow-up were determined. Results Overall, 737 patients were included. The NLR was positively correlated with the severity of coronary lesions as assessed by Gensini score (P P P = 0.025). Conclusions The NLR may be associated with coronary disease severity at baseline but is not associated with adverse outcomes in patients with new-onset ACS. Ethics Approval Number 2019XE0208

Aims Heart failure (HF) is a complex clinical syndrome with multiple comorbidities. Cognitive impairment, stress, anxiety, depression, and lower quality of life are prevalent in HF. Herein, we explore the interplay between these parameters and study their value to predict major adverse cardiovascular events (MACEs) and health‐related quality of life (HrQoL) in patients with HF with reduced ejection fraction using guideline recommended assessment tools. Methods and results We conducted a longitudinal study using a sample of 65 patients from two hospitals. A battery of tests was applied to assess cognition [Montreal Cognitive Assessment (MoCA)], stress (Perceived Stress Scale‐10), anxiety, and depression (Hospital Anxiety and Depression Scale) at baseline. MACEs were registered using clinical records. HrQoL was estimated using the Kansas City Cardiomyopathy Questionnaire (KCCQ). A descriptive statistical analysis was conducted, and multiple linear and Cox regression models conducted to determine the predictive value of neurocognitive parameters and HrQoL in MACE. Both MoCA [hazard ratio = 0.906 (0.829–0.990); P = 0.029] and KCCQ scores were predictors of MACE, but not of overall mortality. Anxiety, depression, and stress scores did not predict MACE. However, anxiety (β = −0.326; P = 0.012) and depression levels (β = −0.309; P = 0.014) were independent predictors of the KCCQ score. Conclusions The MoCA score and HrQoL were predictors of MACE‐free survival. Anxiety and depression were good predictors of HrQoL, but not of MACE‐free survival.

Introduction Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood. Methods Using data from the Dialysis Outcomes and Practice Pattern Study in Japan (J-DOPPS) phases 1, 2, 3, 4, and 5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction (RERI), which is defined as a departure from the additivity of effects. Results A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. As the IDWG increased, the lowest point estimation in each IDWG category tended to shift to the lower hemoglobin concentration categories. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥10.0 g/dl to, Graphical abstract

Daniel A Duprez,1 Yehuda Handelsman,2 Michael Koren3 1Cardiovascular Division, School of Medicine, University of Minnesota, Minneapolis, MN, USA; 2Metabolic Institute of America, Tarzana, CA, USA; 3Jacksonville Center for Clinical Research, Jacksonville, FL, USACorrespondence: Daniel A DuprezCardiovascular Division, School of Medicine, University of Minnesota, MMC 508, Minneapolis, MN 55455, USATel +1 612 624 4948Fax +1 612 626 4611Email dupre007@umn.eduAbstract: Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide and poses an ongoing challenge with the aging population. Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), and the expert consensus is the use of statin therapy (if tolerated) as first line for LDL-C reduction. However, patients with ASCVD may experience recurrent ischemic events despite receiving maximally tolerated statin therapy, including those whose on-treatment LDL-C remains ≥ 70 mg/dL, patients with familial hypercholesterolemia, high-risk subgroups with comorbidities such as diabetes mellitus, and those who have an intolerance to statin therapy. Optimal therapeutic strategies for this unmet need should deploy aggressive lipid lowering to minimize the contribution of dyslipidemia to their CV risk, particularly for very high-risk populations with additional risk factors beyond hypercholesterolemia and established ASCVD. To understand the current clinical climate and guidelines regarding ASCVD, we primarily searched PubMed for articles published in English regarding lipid-lowering therapies and CV risk reduction, including emerging therapies, and CV outcomes trials with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This review discusses the findings of recent clinical trial evidence for CV risk reduction with cholesterol-lowering therapies, with a focus on CV outcomes trials with PCSK9 inhibitors, and considers the impact of the study results for secondary prevention and future strategies in patients with hypercholesterolemia and CV risk despite maximally tolerated statin therapy.Keywords: atherosclerotic cardiovascular disease, hypercholesterolemia, secondary prevention, low-density lipoprotein cholesterol, major adverse cardiovascular events

Aims Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function. ................................................................................................................................................................................................... Methods ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite and results intensive statin treatment. Estimated glomerular filtration rate (eGFR) _90 mL/min/1.73 m (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670–0.919; P = 0.003) and 60 to 60 mL/min/1.73 m 2 2 2 2, The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.

Background Visfatin is an adipokine that related with the inflammation in atherosclerosis and the destabilization of atherosclerotic plaque. The aim of this study was to observe the relationship between visfatin and major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients. Methods We enrolled a total of 238 patients (183 AMI and 55 control) who underwent coronary angiography. Patients with AMI were followed for an average of 19.3 months and 159 patients were finally included in the study. Results It was observed patients with AMI had higher serum visfatin levels than controls. The total incidence of MACEs was 11.32% (18/159) in AMI patients. After calculation of the Youden index, the best cut-off value of visfatin on the curve of receiver-operating characteristic was 8.799 ng/mL for predicting the occurrence of MACEs. The occurrence of MACEs was elevated in high-visfatin group (≥8.799 ng/mL) compared with low-visfatin group (≤8.799 ng/mL). The time to MACEs was correlated with visfatin (HR = 1.235, 95%CI 1.051–1.451, P = 0.01) and high-visfatin group had an earlier time to MACEs and a shorter time of cumulative survival. Conclusions Increased serum visfatin levels were observed in AMI patients, and correlated with an earlier onset and higher incidence of MACEs.

Background There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients. Methods A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike’s information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p p p p p = 0.04) compared to that of the model with SSII alone. The net reclassification and integrated discrimination of the SSII alone model improved significantly with ESR (NRI = 0.0319, p p Conclusions The prognostic model containing SSII, which is an independent risk factor of MACE, had a significantly enhanced predictive probability with the addition of ESR.

Background Recent cohort studies evaluated the association between some previously identified high-risk ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] and risk of major adverse cardiovascular events in adult population. Objective The objective of this meta-analysis was to investigate the magnitude of such associations. Methods We searched publication databases using appropriate keywords to identify cohort studies (published up to July 30, 2019), in which association between previously identified high-risk ceramides and major adverse cardiovascular events was reported. Data from eligible studies were extracted and meta-analysis was performed using random-effects modeling. Results Seven cohort studies with aggregate data on 29,818 individuals (2736 new cases of cardiovascular events over a median follow-up of 6 years) were included. Higher plasma levels of Cer(d18:1/16:0) (random effects hazard ratio [HR] per standard deviation 1.21, 95% confidence interval [CI] 1.11–1.32, I2 = 88%), Cer(d18:1/18:0) (HR 1.19, 95% CI 1.10–1.27, I2 = 68%), and Cer(d18:1/24:1) (HR 1.17, 95% CI 1.08–1.27, I2 = 83%) were associated with major adverse cardiovascular events. Conversely, no association with plasma levels of Cer(d18:1/22:0) (HR 1.14 95% CI 0.88–1.47, I2 = 88%) and Cer(d18:1/24:0) (HR 0.97, 95% CI 0.89–1.05, I2 = 73%) was found. Subgroup analyses did not substantially modify the findings. Conclusions Higher plasma levels of Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1) were associated with major adverse cardiovascular events, whereas plasma levels of Cer(d18:1/22:0) and Cer(d18:1/24:0) were not. Additional research is required to elucidate the different role of ceramides on pathways involved in cardiovascular disease.

Background There is a paucity of contemporary data assessing the implications of atrial fibrillation (AF) on major adverse cardiovascular events (MACE) in patients with or at high‐risk for atherosclerotic disease managed in routine practice. Hypothesis We sought to evaluate the 4‐year incidence of MACE in patients with or at risk of atherosclerotic disease in the presence of AF. Methods Using US MarketScan data, we identified AF patients ≥45 years old with billing codes indicating established coronary artery disease, cerebrovascular disease, or peripheral artery disease or the presence of ≥3 risk factors for atherosclerotic disease from January 1, 2013 to December 31, 2013 with a minimum of 4‐years of available follow‐up. We calculated the 4‐year incidence of MACE (cardiovascular death or hospitalization with a primary billing code for myocardial infarction or ischemic stroke). Patients were further stratified by CHA2DS2‐VASc score and oral anticoagulation (OAC) use at baseline. Results We identified 625,951 patients with 4‐years of follow‐up, of which 77,752 (12.4%) had comorbid AF. The median (25%, 75% range) CHA2DS2‐VASc score was 4 (3, 5) and 64% of patients received an OAC at baseline. The incidence of MACE increased as CHA2DS2‐VASc scores increased (P‐interaction