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Browsing by Author "Vavlukis, Marija (14038383200)"

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    Acute coronary syndrome: The risk to young women
    (2017)
    Ricci, Beatrice (56011398600)
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    Cenko, Edina (55651505300)
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    Vasiljevic, Zorana (6602641182)
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    Stankovic, Goran (59150945500)
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    Kedev, Sasko (23970691700)
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    Kalpak, Oliver (25626262100)
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    Vavlukis, Marija (14038383200)
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    Zdravkovic, Marija (24924016800)
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    Hinic, Sasa (55208518100)
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    Milicic, Davor (56503365500)
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    Manfrini, Olivia (6505860414)
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    Badimon, Lina (7102141956)
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    Bugiardini, Raffaele (26541113500)
    Background--Although acute coronary syndrome (ACS) mainly occurs in patients > 50 years, younger patients can be affected as well. We used an age cutoff of 45 years to investigate clinical characteristics and outcomes of "young" patients with ACS. Methods and Results--Between October 2010 and April 2016, 14 931 patients with ACS were enrolled in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry. Of these patients, 1182 (8%) were aged ≤45 years (mean age, 40.3 years; 15.8% were women). The primary end point was 30-day all-cause mortality. Percentage diameter stenosis of ≤50% was defined as insignificant coronary disease. ST-segment-elevation myocardial infarction was the most common clinical manifestation of ACS in the young cases (68% versus 59.6%). Young patients had a higher incidence of insignificant coronary artery disease (11.4% versus 10.1%) and lesser extent of significant disease (single vessel, 62.7% versus 46.6%). The incidence of 30-day death was 1.3% versus 6.9% for the young and older patients, respectively. After correction for baseline and clinical differences, age ≤45 years was a predictor of survival in men (odds ratio, 0.24; 95% confidence interval, 0.10-0.58), but not in women (odds ratio, 1.35; 95% confidence interval, 0.50-3.62). This pattern of reversed risk among sexes held true after multivariable correction for in-hospital medications and reperfusion therapy. Moreover, younger women had worse outcomes than men of a similar age (odds ratio, 6.03; 95% confidence interval, 2.07-17.53). Conclusion--ACS at a young age is characterized by less severe coronary disease and high prevalence of ST-segment-elevation myocardial infarction. Women have higher mortality than men. Young age is an independent predictor of lower 30-day mortality in men, but not in women. © 2017 The Authors.
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    Age and sex differences in the efficacy of early invasive strategy for non-ST-elevation acute coronary syndrome: A comparative analysis in stable patients
    (2025)
    Cenko, Edina (55651505300)
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    Bergami, Maria (57204641344)
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    Yoon, Jinsung (57192154835)
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    Vadalà, Giuseppe (57203403924)
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    Kedev, Sasko (23970691700)
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    Kostov, Jorgo (7801480082)
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    Vavlukis, Marija (14038383200)
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    Vraynko, Elif (59476615900)
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    Miličić, Davor (56503365500)
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    Vasiljevic, Zorana (6602641182)
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    Zdravkovic, Marija (24924016800)
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    Galassi, Alfredo R. (7004438532)
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    Manfrini, Olivia (6505860414)
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    Bugiardini, Raffaele (26541113500)
    Objective: Previous works have struggled to clearly define sex-specific outcomes based on initial management in NSTE-ACS patients. We examined if early revascularization (<24 h) versus conservative strategy impacts differently based on sex and age in stable NSTE-ACS patients upon hospital admission. Methods: We identified 8905 patients with diagnosis of non‐ST elevation acute coronary syndromes (NSTE-ACS) in the ISACS-TC database. Patients with cardiac arrest, hemodynamic instability, and serious ventricular arrhythmias were excluded. The final cohort consisted of 7589 patients. The characteristics between groups were adjusted using inverse probability of treatment weighting models. Primary outcome measure was all-cause 30-day mortality. Risk ratios (RRs) with their 95 % CIs were employed. Results: Of the 7589 NSTE-ACS patients identified, 2450 (32.3 %) were women. The data show a notable reduction in mortality for the older women (aged 65 years and older) undergoing early invasive strategy compared to those receiving an initial conservative (3.0 % versus 5.1 %; RR: 0.57; 95 % CI: 0.32 – 0.99) Conversely, younger women did not exhibit a significant association between early invasive strategy and mortality reduction (2.0 % versus 0.9 %; RR: 2.27; 95 % CI: 0.73 – 7.04). For men, age stratification did not markedly alter the observed benefits of an early invasive strategy over a conservative approach in the overall population, with reduced death rates in both older (3.1 % versus 5.7 %; RR: 0.52; 95 % CI: 0.34 – 0.80) and younger age groups (0.8 % versus 1.7 %; RR: 0.46; 95 % CI: 0.22 – 0.94). These age and sex-specific mortality patterns did not significantly change within subgroups stratified by the presence of NSTEMI, or a GRACE risk score>140. Conclusion: Early coronary revascularization is associated with improved 30-day survival in older men and women and younger men who present to hospital in stable conditions after NSTE-ACS. It does not confer a survival advantage in young women. Further studies are needed to more accurately risk-stratify young women to guide treatment strategies. Registration: ClinicalTrials.gov: NCT01218776 © 2025 The Author(s)
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    Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors
    (2020)
    Bugiardini, Raffaele (26541113500)
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    Pavasović, Saša (57208482898)
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    Yoon, Jinsung (57192154835)
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    van der Schaar, Mihaela (35605361700)
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    Kedev, Sasko (23970691700)
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    Vavlukis, Marija (14038383200)
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    Vasiljevic, Zorana (6602641182)
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    Bergami, Maria (57204641344)
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    Miličić, Davor (56503365500)
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    Manfrini, Olivia (6505860414)
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    Cenko, Edina (55651505300)
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    Badimon, Lina (7102141956)
    Background: Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. Methods: We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. Findings: The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65–0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89–1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56–0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65–1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59–2·35) Interpretation: Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required. Funding: None. © 2020 The Authors
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    Cardiovascular disease and COVID-19: A consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA)
    (2021)
    Cenko, Edina (55651505300)
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    Badimon, Lina (7102141956)
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    Bugiardini, Raffaele (26541113500)
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    Claeys, Marc J (7102514922)
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    De Luca, Giuseppe (55586620900)
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    De Wit, Cor (7005808759)
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    Derumeaux, Geneviève (55699348000)
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    Dorobantu, Maria (6604055561)
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    Duncker, Dirk J (7005277014)
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    Eringa, Etto C (6507199239)
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    Gorog, Diana A (7003699023)
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    Hassager, Christian (7005846737)
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    Heinzel, Frank R (7005851989)
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    Huber, Kurt (35376715600)
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    Manfrini, Olivia (6505860414)
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    Milicic, Davor (56503365500)
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    Oikonomou, Evangelos (36717891800)
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    Padro, Teresa (6701424923)
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    Trifunovic-Zamaklar, Danijela (9241771000)
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    Vasiljevic-Pokrajcic, Zorana (6602641182)
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    Vavlukis, Marija (14038383200)
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    Vilahur, Gemma (57205093142)
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    Tousoulis, Dimitris (35399054300)
    The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance. © 2021 Published on behalf of the European Society of Cardiology. All rights reserved.
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    Comparison of early versus delayed oral β blockers in acute coronary syndromes and effect on outcomes
    (2016)
    Bugiardini, Raffaele (26541113500)
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    Cenko, Edina (55651505300)
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    Ricci, Beatrice (56011398600)
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    Vasiljevic, Zorana (6602641182)
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    Dorobantu, Maria (6604055561)
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    Kedev, Sasko (23970691700)
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    Vavlukis, Marija (14038383200)
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    Kalpak, Oliver (25626262100)
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    Puddu, Paolo Emilio (7101784080)
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    Gustiene, Olivija (12778547000)
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    Trninic, Dijana (56009277500)
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    Knežević, Božidarka (23474019600)
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    Miličić, Davor (56503365500)
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    Gale, Christopher P. (35837808000)
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    Manfrini, Olivia (6505860414)
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    Koller, Akos (7102499922)
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    Badimon, Lina (7102141956)
    The aim of this study was to determine if earlier administration of oral β blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous β blockers or remained free of any β blocker treatment during hospital stay, 23 as timing of oral β blocker administration was unknown, and 182 patients because they died before oral β blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral β blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early β blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early β blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score-matched analyses. In conclusion, in patients with ACSs, earlier administration of oral β blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen. © 2016 Elsevier Inc. All rights reserved.
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    Early coronary revascularization among 'stable' patients with non-ST-segment elevation acute coronary syndromes: the role of diabetes and age
    (2024)
    Fabin, Natalia (57218175196)
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    Cenko, Edina (55651505300)
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    Bergami, Maria (57204641344)
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    Yoon, Jinsung (57192154835)
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    Vadalà, Giuseppe (57203403924)
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    Mendieta, Guiomar (56248226000)
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    Kedev, Sasko (23970691700)
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    Kostov, Jorgo (7801480082)
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    Vavlukis, Marija (14038383200)
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    Vraynko, Elif (59476615900)
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    Miličić, Davor (56503365500)
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    Vasiljevic, Zorana (6602641182)
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    Zdravkovic, Marija (24924016800)
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    Badimon, Lina (7102141956)
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    Galassi, Alfredo R. (7004438532)
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    Manfrini, Olivia (6505860414)
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    Bugiardini, Raffaele (26541113500)
    Aims: To investigate the impact of an early coronary revascularization (<24 h) compared with initial conservative strategy on clinical outcomes in diabetic patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who are in stable condition at hospital admission. Methods and results: The International Survey of Acute Coronary Syndromes database was queried for a sample of diabetic and nondiabetic patients with diagnosis of NSTE-ACS. Patients with cardiac arrest, haemodynamic instability, and serious ventricular arrhythmias were excluded. The characteristics between groups were adjusted using logistic regression and inverse probability of treatment weighting models. Primary outcome measure was all-cause 30-day mortality. Risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were employed. Of the 7589 NSTE-ACS patients identified, 2343 were diabetics. The data show a notable reduction in mortality for the elderly (>65 years) undergoing early revascularization compared to those receiving an initial conservative strategy both in the diabetic (3.3% vs. 6.7%; RR: 0.48; 95% CI: 0.28-0.80) and nondiabetic patients (2.7% vs. 4.7%: RR: 0.57; 95% CI: 0.36-0.90). In multivariate analyses, diabetes was a strong independent predictor of mortality in the elderly (OR: 1.43; 95% CI: 1.03-1.99), but not in the younger patients (OR: 1.04; 95% CI: 0.53-2.06). Conclusion: Early coronary revascularization does not lead to any survival advantage within 30 days from admission in young NSTE-ACS patients who present to hospital in stable conditions with and without diabetes. An early invasive management strategy may be best reserved for the elderly. Factors beyond revascularization are of considerable importance for outcome in elderly diabetic subjects with NSTE-ACS. © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.
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    ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'
    (2020)
    Padro, Teresa (6701424923)
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    Manfrini, Olivia (6505860414)
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    Bugiardini, Raffaele (26541113500)
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    Canty, John (7005042319)
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    Cenko, Edina (55651505300)
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    De Luca, Giuseppe (55586620900)
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    Duncker, Dirk J. (7005277014)
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    Eringa, Etto C. (6507199239)
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    Koller, Akos (7102499922)
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    Tousoulis, Dimitris (35399054300)
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    Trifunovic, Danijela (9241771000)
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    Vavlukis, Marija (14038383200)
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    De Wit, Cor (7005808759)
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    Badimon, Lina (7102141956)
    Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with 'normal or near normal' coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.
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    Functional and structural adaptations of the coronary macro- and microvasculature to regular aerobic exercise by activation of physiological, cellular, and molecular mechanisms: ESC Working Group on Coronary Pathophysiology and Microcirculation position paper
    (2022)
    Koller, Akos (7102499922)
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    Laughlin, M. Harold (55663782800)
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    Cenko, Edina (55651505300)
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    De Wit, Cor (7005808759)
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    Tóth, Kálmán (7202014152)
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    Bugiardini, Raffaele (26541113500)
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    Trifunovits, Danijela (57438313800)
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    Vavlukis, Marija (14038383200)
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    Manfrini, Olivia (6505860414)
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    Lelbach, Adam (8652522900)
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    Dornyei, Gabriella (6701614133)
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    Padro, Teresa (6701424923)
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    Badimon, Lina (7102141956)
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    Tousoulis, Dimitris (35399054300)
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    Gielen, Stephan (7005725390)
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    Duncker, Dirk J (7005277014)
    Regular aerobic exercise (RAEX) elicits several positive adaptations in all organs and tissues of the body, culminating in improved health and well-being. Indeed, in over half a century, many studies have shown the benefit of RAEX on cardiovascular outcome in terms of morbidity and mortality. RAEX elicits a wide range of functional and structural adaptations in the heart and its coronary circulation, all of which are to maintain optimal myocardial oxygen and nutritional supply during increased demand. Although there is no evidence suggesting that oxidative metabolism is limited by coronary blood flow (CBF) rate in the normal heart even during maximal exercise, increased CBF and capillary exchange capacities have been reported. Adaptations of coronary macro- and microvessels include outward remodelling of epicardial coronary arteries, increased coronary arteriolar size and density, and increased capillary surface area. In addition, there are adjustments in the neural and endothelial regulation of coronary macrovascular tone. Similarly, there are several adaptations at the level of microcirculation, including enhanced (such as nitric oxide mediated) smooth muscle-dependent pressure-induced myogenic constriction and upregulated endothelium-dependent/shear-stress-induced dilation, increasing the range of diameter change. Alterations in the signalling interaction between coronary vessels and cardiac metabolism have also been described. At the molecular and cellular level, ion channels are key players in the local coronary vascular adaptations to RAEX, with enhanced activation of influx of Ca2+ contributing to the increased myogenic tone (via voltage-gated Ca2+ channels) as well as the enhanced endothelium-dependent dilation (via TRPV4 channels). Finally, RAEX elicits a number of beneficial effects on several haemorheological variables that may further improve CBF and myocardial oxygen delivery and nutrient exchange in the microcirculation by stabilizing and extending the range and further optimizing the regulation of myocardial blood flow during exercise. These adaptations also act to prevent and/or delay the development of coronary and cardiac diseases. © 2021 Published on behalf of the European Society of Cardiology. All rights reserved.
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    Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers
    (2023)
    Antoniades, Charalambos (35412194900)
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    Tousoulis, Dimitris (35399054300)
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    Vavlukis, Marija (14038383200)
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    Fleming, Ingrid (7102053742)
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    Duncker, Dirk J. (7005277014)
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    Eringa, Etto (6507199239)
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    Manfrini, Olivia (6505860414)
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    Antonopoulos, Alexios S. (25931366200)
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    Oikonomou, Evangelos (36717891800)
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    Padró, Teresa (6701424923)
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    Trifunovic-Zamaklar, Danijela (9241771000)
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    De Luca, Giuseppe (55586620900)
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    Guzik, Tomasz (7003467849)
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    Cenko, Edina (55651505300)
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    Djordjevic-Dikic, Ana (57003143600)
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    Crea, Filippo (57213692073)
    Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a ‘biosensor’ of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention. © 2023 Oxford University Press. All rights reserved.
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    Relationship between azithromycin and cardiovascular outcomes in unvaccinated patients with covid-19 and preexisting cardiovascular disease
    (2023)
    Bergami, Maria (57204641344)
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    Manfrini, Olivia (6505860414)
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    Nava, Stefano (7005445868)
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    Caramori, Gaetano (7003847659)
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    Yoon, Jinsung (57192154835)
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    Badimon, Lina (7102141956)
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    Cenko, Edina (55651505300)
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    David, Antonio (7402606823)
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    Demiri, Ilir (55481504100)
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    Dorobantu, Maria (6604055561)
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    Fabin, Natalia (57218175196)
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    Gheorghe-Fronea, Oana (57204444889)
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    Jankovic, Radmilo (15831502700)
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    Kedev, Sasko (23970691700)
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    Ladjevic, Nebojsa (16233432900)
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    Lasica, Ratko (14631892300)
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    Loncar, Goran (55427750700)
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    Mancuso, Giuseppe (7004330020)
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    Mendieta, Guiomar (56248226000)
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    Miličić, Davor (56503365500)
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    Mjehović, Petra (58266126900)
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    Pašalić, Marijan (36010787900)
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    Petrović, Milovan (16234216100)
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    Poposka, Lidija (23498648800)
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    Scarpone, Marialuisa (57204641989)
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    Stefanovic, Milena (57216929189)
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    Van Der Schaar, Mihaela (35605361700)
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    Vasiljevic, Zorana (6602641182)
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    Vavlukis, Marija (14038383200)
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    Pittao, Maria Laura Vega (57194336728)
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    Vukomanovic, Vladan (57144261800)
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    Zdravkovic, Marija (24924016800)
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    Bugiardini, Raffaele (26541113500)
    BACKGROUND: Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. METHODS AND RESULTS: This study was conducted using data from the ISACS-COVID- 19 (International Survey of Acute Coronavirus Syndromes-COVID- 19) registry. Patients with a confirmed diagnosis of SARS-CoV- 2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69–1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42–0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75–2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34–3.90]). CONCLUSIONS: These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. REGISTRATION: URL: Https://www.clini caltr ials.gov; Unique identifier: NCT05188612. © 2023 The Authors.
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    Sex differences and disparities in cardiovascular outcomes of COVID-19
    (2023)
    Bugiardini, Raffaele (26541113500)
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    Nava, Stefano (7005445868)
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    Caramori, Gaetano (7003847659)
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    Yoon, Jinsung (57192154835)
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    Badimon, Lina (7102141956)
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    Bergami, Maria (57204641344)
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    Cenko, Edina (55651505300)
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    David, Antonio (7402606823)
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    Demiri, Ilir (55481504100)
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    Dorobantu, Maria (6604055561)
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    Fronea, Oana (57219160643)
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    Jankovic, Radmilo (15831502700)
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    Kedev, Sasko (23970691700)
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    Ladjevic, Nebojsa (16233432900)
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    Lasica, Ratko (14631892300)
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    Loncar, Goran (55427750700)
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    Mancuso, Giuseppe (7004330020)
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    Mendieta, Guiomar (56248226000)
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    Miličić, Davor (56503365500)
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    Mjehović, Petra (58266126900)
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    Pašalić, Marijan (36010787900)
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    Petrović, Milovan (16234216100)
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    Poposka, Lidija (23498648800)
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    Scarpone, Marialuisa (57204641989)
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    Stefanovic, Milena (57216929189)
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    van der Schaar, Mihaela (35605361700)
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    Vasiljevic, Zorana (6602641182)
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    Vavlukis, Marija (14038383200)
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    Pittao, Maria Laura Vega (57194336728)
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    Vukomanovic, Vladan (57144261800)
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    Zdravkovic, Marija (24924016800)
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    Manfrini, Olivia (6505860414)
    Aims Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. Methods This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey and results of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71–0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90–1.42) and 0.86 (95% CI: 0.70–1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73–2.98; 3.85, 95% CI: 3.21–4.63; and 3.95, 95% CI: 3.04–5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94–1.67 vs. 0.83; 95% CI: 0.59–1.16, pinteraction = 0.04). Conclusions Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.
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    Sex Differences in Heart Failure Following Acute Coronary Syndromes
    (2023)
    Cenko, Edina (55651505300)
    ;
    Manfrini, Olivia (6505860414)
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    Yoon, Jinsung (57192154835)
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    van der Schaar, Mihaela (35605361700)
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    Bergami, Maria (57204641344)
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    Vasiljevic, Zorana (6602641182)
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    Mendieta, Guiomar (56248226000)
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    Stankovic, Goran (59150945500)
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    Vavlukis, Marija (14038383200)
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    Kedev, Sasko (23970691700)
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    Miličić, Davor (56503365500)
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    Badimon, Lina (7102141956)
    ;
    Bugiardini, Raffaele (26541113500)
    Background: There have been conflicting reports regarding outcomes in women presenting with an acute coronary syndrome (ACS). Objectives: The objective of the study was to examine sex-specific differences in 30-day mortality in patients with ACS and acute heart failure (HF) at the time of presentation. Methods: This was a retrospective study of patients included in the International Survey of Acute Coronary Syndromes-ARCHIVES (ISACS-ARCHIVES; NCT04008173). Acute HF was defined as Killip classes ≥2. Participants were stratified according to ACS presentation: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Differences in 30-day mortality and acute HF presentation at admission between sexes were examined using inverse propensity weighting based on the propensity score. Estimates were compared by test of interaction on the log scale. Results: A total of 87,812 patients were included, of whom 30,922 (35.2%) were women. Mortality was higher in women compared with men in those presenting with STEMI (risk ratio [RR]: 1.65; 95% CI: 1.56-1.73) and NSTE-ACS (RR: 1.18; 95% CI: 1.09-1.28; Pinteraction <0.001). Acute HF was more common in women when compared to men with STEMI (RR: 1.24; 95% CI: 1.20-1.29) but not in those with NSTE-ACS (RR: 1.02; 95% CI: 0.97-1.08) (Pinteraction <0.001). The presence of acute HF increased the risk of mortality for both sexes (odds ratio: 6.60; 95% CI: 6.25-6.98). Conclusions: In patients presenting with ACS, mortality is higher in women. The presence of acute HF at hospital presentation increases the risk of mortality in both sexes. Women with STEMI are more likely to present with acute HF and this may, in part, explain sex differences in mortality. These findings may be helpful to improve sex-specific personalized risk stratification. © 2023 The Authors
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    Sex Differences in Heart Failure Following Acute Coronary Syndromes
    (2023)
    Cenko, Edina (55651505300)
    ;
    Manfrini, Olivia (6505860414)
    ;
    Yoon, Jinsung (57192154835)
    ;
    van der Schaar, Mihaela (35605361700)
    ;
    Bergami, Maria (57204641344)
    ;
    Vasiljevic, Zorana (6602641182)
    ;
    Mendieta, Guiomar (56248226000)
    ;
    Stankovic, Goran (59150945500)
    ;
    Vavlukis, Marija (14038383200)
    ;
    Kedev, Sasko (23970691700)
    ;
    Miličić, Davor (56503365500)
    ;
    Badimon, Lina (7102141956)
    ;
    Bugiardini, Raffaele (26541113500)
    Background: There have been conflicting reports regarding outcomes in women presenting with an acute coronary syndrome (ACS). Objectives: The objective of the study was to examine sex-specific differences in 30-day mortality in patients with ACS and acute heart failure (HF) at the time of presentation. Methods: This was a retrospective study of patients included in the International Survey of Acute Coronary Syndromes-ARCHIVES (ISACS-ARCHIVES; NCT04008173). Acute HF was defined as Killip classes ≥2. Participants were stratified according to ACS presentation: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Differences in 30-day mortality and acute HF presentation at admission between sexes were examined using inverse propensity weighting based on the propensity score. Estimates were compared by test of interaction on the log scale. Results: A total of 87,812 patients were included, of whom 30,922 (35.2%) were women. Mortality was higher in women compared with men in those presenting with STEMI (risk ratio [RR]: 1.65; 95% CI: 1.56-1.73) and NSTE-ACS (RR: 1.18; 95% CI: 1.09-1.28; Pinteraction <0.001). Acute HF was more common in women when compared to men with STEMI (RR: 1.24; 95% CI: 1.20-1.29) but not in those with NSTE-ACS (RR: 1.02; 95% CI: 0.97-1.08) (Pinteraction <0.001). The presence of acute HF increased the risk of mortality for both sexes (odds ratio: 6.60; 95% CI: 6.25-6.98). Conclusions: In patients presenting with ACS, mortality is higher in women. The presence of acute HF at hospital presentation increases the risk of mortality in both sexes. Women with STEMI are more likely to present with acute HF and this may, in part, explain sex differences in mortality. These findings may be helpful to improve sex-specific personalized risk stratification. © 2023 The Authors
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    Sex differences in modifiable risk factors and severity of coronary artery disease
    (2020)
    Manfrini, Olivia (6505860414)
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    Yoon, Jinsung (57192154835)
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    van der Schaar, Mihaela (35605361700)
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    Kedev, Sasko (23970691700)
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    Vavlukis, Marija (14038383200)
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    Stankovic, Goran (59150945500)
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    Scarpone, Marialuisa (57204641989)
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    Miličić, Davor (56503365500)
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    Vasiljevic, Zorana (6602641182)
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    Badimon, Lina (7102141956)
    ;
    Cenko, Edina (55651505300)
    ;
    Bugiardini, Raffaele (26541113500)
    BACKGROUND: It is still unknown whether traditional risk factors may have a sex-specific impact on coronary artery disease (CAD) burden. METHODS AND RESULTS: We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries; Clini​calTr​ials.gov, NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. Relative risk (RR) ratios and 95% CIs were calculated from the ratio of the abso-lute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49 (95% CI, 0.41–0.60) and among those with diabetes mellitus was 0.89 (95% CI, 0.62–1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41–0.61) in nonsmokers to 0.75 (95% CI, 0.54–1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48–2.07). No sex differences in mortality were observed in patients with nonobstructive CAD. CONCLUSIONS: Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions. © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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    Sex-Related Differences in Heart Failure After ST-Segment Elevation Myocardial Infarction
    (2019)
    Cenko, Edina (55651505300)
    ;
    van der Schaar, Mihaela (35605361700)
    ;
    Yoon, Jinsung (57192154835)
    ;
    Manfrini, Olivia (6505860414)
    ;
    Vasiljevic, Zorana (6602641182)
    ;
    Vavlukis, Marija (14038383200)
    ;
    Kedev, Sasko (23970691700)
    ;
    Miličić, Davor (56503365500)
    ;
    Badimon, Lina (7102141956)
    ;
    Bugiardini, Raffaele (26541113500)
    Background: ST-segment elevation myocardial infarction (STEMI) complicated by symptoms of acute de novo heart failure is associated with excess mortality. Whether development of heart failure and its outcomes differ by sex is unknown. Objectives: This study sought to examine the relationships among sex, acute heart failure, and related outcomes after STEMI in patients with no prior history of heart failure recorded at baseline. Methods: Patients were recruited from a network of hospitals in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776). Main outcome measures were incidence of Killip class ≥II at hospital presentation and risk-adjusted 30-day mortality rates were estimated using inverse probability of weighting and logistic regression models. Results: This study included 10,443 patients (3,112 women). After covariate adjustment and matching for age, cardiovascular risk factors, comorbidities, disease severity, and delay to hospital presentation, the incidence of de novo heart failure at hospital presentation was significantly higher for women than for men (25.1% vs. 20.0%, odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.21 to 1.48). Women with de novo heart failure had higher 30-day mortality than did their male counterparts (25.1% vs. 20.6%; OR: 1.29; 95% CI: 1.05 to 1.58). The sex-related difference in mortality rates was still apparent in patients with de novo heart failure undergoing reperfusion therapy after hospital presentation (21.3% vs. 15.7%; OR: 1.45; 95% CI: 1.07 to 1.96). Conclusions: Women are at higher risk to develop de novo heart failure after STEMI and women with de novo heart failure have worse survival than do their male counterparts. Therefore, de novo heart failure is a key feature to explain mortality gap after STEMI among women and men. © 2019 American College of Cardiology Foundation
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    Traditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study
    (2024)
    Bugiardini, Raffaele (26541113500)
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    Cenko, Edina (55651505300)
    ;
    Yoon, Jinsung (57192154835)
    ;
    Bergami, Maria (57204641344)
    ;
    Vasiljevic, Zorana (6602641182)
    ;
    Mendieta, Guiomar (56248226000)
    ;
    Zdravkovic, Marija (24924016800)
    ;
    Vavlukis, Marija (14038383200)
    ;
    Kedev, Sasko (23970691700)
    ;
    Miličić, Davor (56503365500)
    ;
    Badimon, Lina (7102141956)
    ;
    Manfrini, Olivia (6505860414)
    Background: The age-standardized death rates under 65 years from ischemic heart disease in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are not completely recognized. The aim of the present study was to address this issue by collecting and analyzing data from a large, multinational cohort. Methods: We enrolled 70,953 Caucasian patients with first acute coronary syndrome, from 36 urban hospital in 7 South Eastern European countries and assessed their life expectancy free of acute coronary syndrome and mortality within 30 days after hospital admission from acute coronary syndrome as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes and hypercholesterolemia) stratified according to sex. Findings: Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of acute coronary syndrome (women: from 67.1 ± 12.0 to 61.9 ± 10.3 years; r = −0.089; p < 0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r = −0.096; p < 0.001). Premature acute coronary syndrome (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (RRs: 3.96; 95% CI: 3.72–4.20 and 1.31; 95% CI: 1.25–1.38, respectively) and men (RRs: 2.82; 95% CI: 2.71–2.93 and 1.39; 95% CI: 1.34–1.45, respectively). Diabetes was most strongly associated with death from premature acute coronary syndrome either in women (RR: 1.52; 95% CI: 1.29–1.79) or men (RR: 1.63; 95% CI: 1.41–1.89). Interpretation: Public health policies in South Eastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature ischemic heart disease. Funding: None. © 2023 The Author(s)

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