Publications by authors named "Zorana Vasiljevic"

70 Publications

Concerns about the use of digoxin in acute coronary syndromes.

Eur Heart J Cardiovasc Pharmacother 2021 Jul 12. Epub 2021 Jul 12.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Aims: The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases.

Methods And Results: Of the 25,187 patients presenting with acute HF (Killip class ≥ 2) in the International Survey of Acute Coronary Syndromes (ISACS)-Archives (NCT04008173) registry, 4,722 (18.7%) received digoxin on hospital admission. The main outcome measure was all cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it (33.8% vs. 29.2%; relative risk [RR] ratio:1.24;95% confidence interval [CI]: 1.12-1.37). Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio 1.20; 95% CI:1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratios:1.26; 95% CI: 1.10 to 1.45 in women and RR:1.21; 95% CI: 1.06 to 1.39 in men) and those in sinus rhythm at admission (RR ratios:1.34; 95% CI 1.15 to 1.54 in women and 1.26; 95% CI 1.10 to 1.45 in men).

Conclusion: Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.
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http://dx.doi.org/10.1093/ehjcvp/pvab055DOI Listing
July 2021

Smoking and sex differences in first manifestation of cardiovascular disease.

Atherosclerosis 2021 08 26;330:43-51. Epub 2021 Jun 26.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. Electronic address:

Background And Aims: An increasing proportion of women believe that smoking few cigarettes daily substantially reduces their risk of developing cardiovascular (CV) related disorders. The effect of low intensity smoking is still largely understudied. We investigated the relation among sex, age, cigarette smoking and ST segment elevation myocardial infarction (STEMI) as initial manifestation of CV disease.

Methods: We analyzed data of 50,713 acute coronary syndrome patients with no prior manifestation of CV disease from the ISACS-Archives (NCT04008173) registry. We compared the rates of STEMI in current smokers (n = 11,530) versus nonsmokers (n = 39,183).

Results: In the young middle age group (<60 years), there was evidence of a more harmful effect in women compared with men (RR ratios: 1.90; 95% CI: 1.69-2.14 versus 1.68; 95% CI: 1.56-1.80). This association persisted even in women who smoked 1 to 10 packs per year (RR ratios: 2.02; 95% CI: 1.65 to 2.48 versus 1.38; 95% CI: 1.22 to 1.57). In the older group, rates of STEMI were similar for women and men (RR ratios: 1.36; 95% CI: 1.22-1.53 versus 1.39; 95% CI: 1.28-1.50). STEMI was associated with a twofold higher 30-day mortality rate in young middle age women compared with men of the same age (odds ratios, 5.54; 95% CI, 3.83-8.03 vs. 2.93; 95% CI, 2.33-3.69).

Conclusions: Low intensity smoking provides inadequate protection in young - middle age women as they still have a substantially higher rate of STEMI and related mortality compared with men even smoking less than 10 packs per year. This finding is worrying as more young - middle age women are smoking, and rates of smoking among young-middle age men continue to fall.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.909DOI Listing
August 2021

Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors.

EClinicalMedicine 2020 Oct 20;27:100548. Epub 2020 Sep 20.

Cardiovascular Research Program ICCC, IR-IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, CiberCV-Institute Carlos III, Barcelona, Spain.

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.
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http://dx.doi.org/10.1016/j.eclinm.2020.100548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599315PMC
October 2020

Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease.

J Am Heart Assoc 2020 10 28;9(19):e017235. Epub 2020 Sep 28.

Department of Experimental, Diagnostic and Specialty Medicine University of Bologna Bologna Italy.

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 absolute 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 =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 =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. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01218776.
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http://dx.doi.org/10.1161/JAHA.120.017235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792418PMC
October 2020

Prior Beta-Blocker Therapy for Hypertension and Sex-Based Differences in Heart Failure Among Patients With Incident Coronary Heart Disease.

Hypertension 2020 09 13;76(3):819-826. Epub 2020 Jul 13.

From the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy (R.B., O.M., E.C.).

The usefulness of β-blockers has been questioned for patients who have hypertension without a prior manifestation of coronary heart disease or heart failure. In addition, sex-based differences in the efficacy of β-blockers for prevention of heart failure during acute myocardial ischemia have never been evaluated. We explored whether the effect of β-blocker therapy varied according to the sex among patients with hypertension who have no prior history of cardiovascular disease. Data were drawn from the ISACS (International Survey of Acute Coronary Syndromes)-Archives. The study population consisted of 13 764 patients presenting with acute coronary syndromes. There were 2590 patients in whom hypertension was treated previously with β-blocker (954 women and 1636 men). Primary outcome measure was the incidence of heart failure according to Killip class classification. Subsidiary analyses were conducted to estimate the association between heart failure and all-cause mortality at 30 days. Outcome rates were assessed using the inverse probability of treatment weighting and logistic regression models. Estimates were compared by test of interaction on the log scale. Among patients taking β-blockers before admission, there was an absolute difference of 4.6% between women and men in the rate of heart failure (Killip ≥2) at hospital presentation (21.3% versus 16.7%; relative risk ratio, 1.35 [95% CI, 1.10-1.65]). On the opposite, the rate of heart failure was approximately similar among women and men who did not receive β-blockers (17.2% versus 16.1%; relative risk ratio, 1.09 [95% CI, 0.97-1.21]). The test of interaction identified a significant (=0.034) association between sex and β-blocker therapy. Heart failure was predictive of mortality at 30-day either in women (odds ratio, 7.54 [95% CI, 5.78-9.83]) or men (odds ratio, 9.62 [95% CI, 7.67-12.07]). In conclusion, β-blockers use may be an acute precipitant of heart failure in new-onset coronary heart disease among women, but not men. Heart failure increases the risk of death. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04008173.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15323DOI Listing
September 2020

Sex-Related Differences in Heart Failure After ST-Segment Elevation Myocardial Infarction.

J Am Coll Cardiol 2019 11;74(19):2379-2389

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jacc.2019.08.1047DOI Listing
November 2019

Sex-Specific Treatment Effects After Primary Percutaneous Intervention: A Study on Coronary Blood Flow and Delay to Hospital Presentation.

J Am Heart Assoc 2019 02;8(4):e011190

1 Department of Experimental, Diagnostic and Specialty Medicine University of Bologna Bologna Italy.

Background We hypothesized that female sex is a treatment effect modifier of blood flow and related 30-day mortality after primary percutaneous coronary intervention ( PCI ) for ST -segment-elevation myocardial infarction and that the magnitude of the effect on outcomes differs depending on delay to hospital presentation. Methods and Results We identified 2596 patients enrolled in the ISACS - TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry from 2010 to 2016. Primary outcome was the occurrence of 30-day mortality. Key secondary outcome was the rate of suboptimal post- PCI Thrombolysis in Myocardial Infarction ( TIMI ; flow grade 0-2). Multivariate logistic regression and inverse probability of treatment weighted models were adjusted for baseline clinical covariates. We characterized patient outcomes associated with a delay from symptom onset to hospital presentation of ≤120 minutes. In multivariable regression models, female sex was associated with postprocedural TIMI flow grade 0 to 2 (odds ratio [ OR ], 1.68; 95% CI , 1.15-2.44) and higher mortality ( OR, 1.72; 95% CI , 1.02-2.90). Using inverse probability of treatment weighting, 30-day mortality was higher in women compared with men (4.8% versus 2.5%; OR , 2.00; 95% CI , 1.27-3.15). Likewise, we found a significant sex difference in post- PCI TIMI flow grade 0 to 2 (8.8% versus 5.0%; OR , 1.83; 95% CI , 1.31-2.56). The sex gap in mortality was no longer significant for patients having hospital presentation of ≤120 minutes ( OR , 1.28; 95% CI , 0.35-4.69). Sex difference in post- PCI TIMI flow grade was consistent regardless of time to hospital presentation. Conclusions Delay to hospital presentation and suboptimal post- PCI TIMI flow grade are variables independently associated with excess mortality in women, suggesting complementary mechanisms of reduced survival. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01218776.
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http://dx.doi.org/10.1161/JAHA.118.011190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405653PMC
February 2019

Coronary Microcirculation in Heart Failure with Preserved Systolic Function.

Curr Pharm Des 2018 ;24(25):2960-2966

University of Belgrade, Faculty of Medicine, Belgrade, Serbia.

Background: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF.

Methods: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies.

Results: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients.

Conclusion: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.
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http://dx.doi.org/10.2174/1381612824666180711124131DOI Listing
November 2019

Sex Differences in Outcomes After STEMI: Effect Modification by Treatment Strategy and Age.

JAMA Intern Med 2018 05;178(5):632-639

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Importance: Previous works have shown that women hospitalized with ST-segment elevation myocardial infarction (STEMI) have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI).

Objective: To investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications, and primary PCI in this excess of risk.

Design, Setting, And Participants: From January 2010 to January 2016, a total of 8834 patients were hospitalized and received medical treatment for STEMI in 41 hospitals referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776).

Exposures: Demographics, baseline characteristics, clinical profile, and pharmacological treatment within 24 hours and primary PCI.

Main Outcomes And Measures: Adjusted 30-day mortality rates estimated using inverse probability of treatment weighted (IPTW) logistic regression models.

Results: There were 2657 women with a mean (SD) age of 66.1 (11.6) years and 6177 men with a mean (SD) age of 59.9 (11.7) years included in the study. Thirty-day mortality was significantly higher for women than for men (11.6% vs 6.0%, P < .001). The gap in sex-specific mortality narrowed if restricting the analysis to men and women undergoing primary PCI (7.1% vs 3.3%, P < .001). After multivariable adjustment for comorbidities and treatment covariates, women under 60 had higher early mortality risk than men of the same age category (OR, 1.88; 95% CI, 1.04-3.26; P = .02). The risk in the subgroups aged 60 to 74 years and over 75 years was not significantly different between sexes (OR, 1.28; 95% CI, 0.88-1.88; P = .19 and OR, 1.17; 95% CI, 0.80-1.73; P = .40; respectively). After IPTW adjustment for baseline clinical covariates, the relationship among sex, age category, and 30-day mortality was similar (OR, 1.56 [95% CI, 1.05-2.3]; OR, 1.49 [95% CI, 1.15-1.92]; and OR, 1.21 [95% CI, 0.93-1.57]; respectively).

Conclusions And Relevance: Younger age was associated with higher 30-day mortality rates in women with STEMI even after adjustment for medications, primary PCI, and other coexisting comorbidities. This difference declines after age 60 and is no longer observed in oldest women.
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http://dx.doi.org/10.1001/jamainternmed.2018.0514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145795PMC
May 2018

Oxidative stress markers predict early left ventricular systolic dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention.

Adv Clin Exp Med 2018 Feb;27(2):185-191

Cardiology Clinic, Clinical Centre of Serbia, Belgrade, Serbia.

Background: Despite successful primary percutaneous coronary intervention (PCI) after ST-segment elevation myocardial infarction (STEMI), some patients develop left ventricular systolic dysfunction (LVSD) and acute heart failure (HF). Identifying patients with an increased risk of developing LVSD by means of biomarkers may help select patients requiring more aggressive therapy.

Objectives: The aim of this study was to evaluate the relationship between the levels of oxidative stress markers and development of LVSD and acute HF early after STEMI.

Material And Methods: The study enrolled 148 patients with the first STEMI, who were treated by primary PCI < 12 h from the onset of symptoms. We assessed the impact of different biomarkers for developing LVSD and acute HF (Killip ≥ 2) including: markers of necrosis - peak creatine kinase (CK), markers of myocardial stretch - B-type natriuretic peptide (BNP), inflammatory markers - C-reactive protein (CRP), leucocyte and neutrophil count, as well as oxidative stress markers - total thiol groups, catalase, superoxide dismutase (SOD) and glutathione reductase (GR).

Results: In multivariate analysis, thiol groups, peak CK, anterior wall infarction, and age were predictors of LVEF ≤ 40%. Out of 16 variables significantly associated with the Killip ≥ 2 in univariate logistic regression analysis, 5 appeared to be independently associated with acute HF in multivariate analysis: catalase, BNP, leucocytes, neutrophil count, and size of left atrium.

Conclusions: In this study, we have shown for the first time that thiol groups and catalase are independent predictors of STEMI complication - LVSD and acute HF, respectively. Beside routine used biomarkers of necrosis and myocardial stretch, thiol groups and catalase may provide additional information regarding the risk stratification.
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http://dx.doi.org/10.17219/acem/64464DOI Listing
February 2018

Acute Coronary Syndrome: The Risk to Young Women.

J Am Heart Assoc 2017 12 22;6(12). Epub 2017 Dec 22.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy

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.

Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier: NCT01218776.
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http://dx.doi.org/10.1161/JAHA.117.007519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779054PMC
December 2017

Delayed Care and Mortality Among Women and Men With Myocardial Infarction.

J Am Heart Assoc 2017 Aug 21;6(8). Epub 2017 Aug 21.

Cardiovascular Research Institute (ICCC), CiberCV-Institute Carlos III, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau Autonomous University of Barcelona, Spain.

Background: Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women.

Methods And Results: We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02).

Conclusions: Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01218776.
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http://dx.doi.org/10.1161/JAHA.117.005968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586439PMC
August 2017

Usefulness of NT-proBNP in the Follow-Up of Patients after Myocardial Infarction.

J Med Biochem 2016 Apr 9;35(2):158-165. Epub 2016 May 9.

Cardiology Clinic, Clinical Center of Serbia, Belgrade, Serbia.

Background: Since serial analyses of NT-proBNP in patients with acute coronary syndromes have shown that levels measured during a chronic, later phase are a better predictor of prognosis and indicator of left ventricular function than the levels measured during an acute phase, we sought to assess the association of NT-proBNP, measured 6 months after acute myocardial infarction (AMI), with traditional risk factors, characteristics of in-hospital and early postinfarction course, as well as its prognostic value and optimal cut-points in the ensuing 1-year follow-up.

Methods: Fasting venous blood samples were drawn from 100 ambulatory patients and NT-proBNP concentrations in lithium-heparin plasma were determined using a one-step enzyme immunoassay based on the »sandwich« principle on a Dimension RxL clinical chemistry system (DADE Behring-Siemens). Patients were followed-up for the next 1 year, for the occurrence of new cardiac events.

Results: Median (IQR) level of NT-proBNP was 521 (335-1095) pg/mL. Highest values were mostly associated with cardiac events during the first 6 months after AMI. Negative association with reperfusion therapy for index infarction confirmed its long-term beneficial effect. In the next one-year follow-up of stable patients, multivariate Cox regression analysis revealed the independent prognostic value of NT-proBNP for new-onset heart failure prediction (p=0.014), as well as for new coronary events prediction (p=0.035). Calculation of the AUCs revealed the optimal NT-proBNP cut-points of 800 pg/mL and 516 pg/mL, respectively.

Conclusions: NT-proBNP values 6 months after AMI are mainly associated with the characteristics of early infarction and postinfarction course and can predict new cardiac events in the next one-year follow-up.
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http://dx.doi.org/10.1515/jomb-2016-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346793PMC
April 2016

Invasive versus conservative strategy in acute coronary syndromes: The paradox in women's outcomes.

Int J Cardiol 2016 Nov 30;222:1110-1115. Epub 2016 Jul 30.

Department of Experimental, Diagnostic and Specialty Medicine, Section of Cardiology, University of Bologna, Bologna, Italy. Electronic address:

Background: We explored benefits and risks of an early invasive compared with a conservative strategy in women versus men after non-ST elevation acute coronary syndromes (NSTE-ACS) using the ISACS-TC database.

Methods: From October 2010 to May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258 patients managed with coronary bypass surgery. Of the remaining 3887 patients, 1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day mortality and severe left ventricular dysfunction defined as an ejection fraction <40% at discharge.

Results: Women were older and more likely to exhibit more risk factors and Killip Class ≥2 at admission as compared with men. In patients who underwent PCI, peri-procedural myocardial injury was not different among sexes (3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008) compared with men, whereas those who managed with only routine medical therapy (RMT) did not show any sex difference in outcomes. In multivariable analysis, female sex was associated with favorable outcomes (adjusted HR for the composite endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52).

Conclusions: We observed a more favorable outcome in women than men when patients were managed with RMT. Women and men undergoing PCI have similar outcomes. These data suggest caution in extrapolating the results from men to women in an overall population of patients in the context of different therapeutic strategies.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.211DOI Listing
November 2016

Primary percutaneous coronary intervention in octogenarians.

Int J Cardiol 2016 Nov 2;222:1129-1135. Epub 2016 Aug 2.

Department of Experimental, Diagnostic and Specialty Medicine, Section of Cardiology, University of Bologna, Bologna, Italy.

Background: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI.

Methods: 2225 STEMI patients ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years old (very-elderly). The primary end-point was 30-day mortality.

Results: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30-0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease.

Conclusions: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.204DOI Listing
November 2016

The no-reflow phenomenon in the young and in the elderly.

Int J Cardiol 2016 Nov 2;222:1122-1128. Epub 2016 Aug 2.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy. Electronic address:

Background: The objectives of this study were to evaluate the incidence of no-reflow as independent predictor of adverse events and to assess whether baseline pre-procedural treatment options may affect clinical outcomes.

Methods: Data were derived from the ISACS-TC registry (NCT01218776) from October 2010 to January 2015. No-reflow was defined as post-PCI TIMI flow grades 0-1, in the absence of post-procedural significant (≥25%) residual stenosis, abrupt vessel closure, dissection, perforation, thrombus of the original target lesion, or epicardial spasm. The outcome measure was in-hospital mortality.

Results: No-reflow was identified in 128 of 5997 patients who have undergone PCI (2.1%). On multivariate analysis, patients with no-reflow were more likely to be older (OR: 1.20, 95% CI: 1.01-1.44), to have a history of hypercholesterolemia (OR: 1.95, 95% CI: 1.31-2.91) and to be admitted with a diagnosis of STEMI (OR: 2.96, 95% CI: 1.85-4.72). Angiographic characteristics associated with no-reflow phenomenon were: stenosis ≥50% of the right coronary artery, presence of multivessel disease and pre-procedural TIMI blood flow grades 0-1. No-reflow was highly predictive of in-hospital mortality (17.2% vs. 4.2%; adjusted OR: 4.60, 95% CI: 2.61-8.09). Administration of pre-procedural unfractioned heparin or 600mg clopidogrel loading dose was associated with less incidence of no-reflow (OR: 0.65, 95% CI: 0.43-0.99 and 0.61, 95% CI: 0.37-1.00, respectively). Aspirin, enoxaparin, and 300mg clopidogrel loading dose, did not significantly impact the occurrence of the no-reflow.

Conclusions: We found that pre-procedural administration of 600mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.209DOI Listing
November 2016

Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry.

Int J Cardiol 2016 Aug 29;217 Suppl:S21-6. Epub 2016 Jun 29.

Department of Cardiology, Clinical Emergency Hospital Bucharest, Bucharest, Romania; Bucharest University of Medicine and Pharmacy Carol Davila, Bucharest, Romania. Electronic address:

Background: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients.

Methods: We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame.

Results: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89).

Conclusions: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.227DOI Listing
August 2016

Association between comorbidities and absence of chest pain in acute coronary syndrome with in-hospital outcome.

Int J Cardiol 2016 Aug 28;217 Suppl:S37-43. Epub 2016 Jun 28.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy. Electronic address:

Background: To evaluate the impact of comorbidities on the management and outcomes of acute coronary syndrome (ACS) patients without chest pain/discomfort (i.e. ACS without typical presentation).

Methods: Of the 11,458 ACS patients, enrolled by the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC; ClinicalTrials.gov: NCT01218776), 8.7% did not have typical presentation at the initial evaluation, and 40.2% had comorbidities. The odds of atypical presentation increased proportionally with the number of comorbidities (odds ratio [OR]: 1, no-comorbid; OR: 1.64, 1 comorbidity; OR: 2.52, 2 comorbidities; OR: 4.57, ≥3 comorbidities).

Results: Stratifying the study population by the presence/absence of comorbidities and typical presentation, we found a decreasing trend for use of medications and percutaneous intervention (OR: 1, typical presentation and no-comorbidities; OR: 0.70, typical presentation and comorbidities; OR: 0.23, atypical presentation and no-comorbidities; OR: 0.18, atypical presentation and comorbidities). On the opposite, compared with patients with typical presentation and no-comorbidities (OR: 1, referent), there was an increasing trend (p<0.001) in the risk of death (OR: 2.00, OR: 2.52 and OR: 4.83) in the above subgroups. However, after adjusting for comorbidities, medications and invasive procedures, atypical presentation was not a predictor of in-hospital death. Independent predictors of poor outcome were history of stroke (OR: 2.04), chronic kidney disease (OR: 1.57), diabetes mellitus (OR: 1.49) and underuse of invasive procedures.

Conclusions: In the ISACS-TC, atypical ACS presentation was often associated with comorbidities. Atypical presentation and comorbidities influenced underuse of in-hospital treatments. The latter and comorbidities are related with poor in-hospital outcome, but not atypical presentation, per se.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.221DOI Listing
August 2016

Psychosocial Stress and Risk of Myocardial Infarction: A Case-Control Study in Belgrade (Serbia).

Acta Cardiol Sin 2016 May;32(3):281-9

Institute of Epidemiology;

Background: The purpose of this study was to investigate which psychosocial risk factors show the strongest association with occurrence of myocardial infarction (MI) in the population of Belgrade in peacetime, after the big political changes in Serbia.

Methods: A case-control study was conducted involving 154 consecutive newly diagnosed patients with MI, and 308 controls matched by gender, age, and place of residence.

Results: According to conditional logistic regression analysis, after adjustment for conventional coronary risk factors, the odds ratios (95% confidence intervals) for work-related stressful events, financial stress, deaths and diseases, and general stress were 3.78 (1.83-7.81), 3.80 (1.96-7.38), 1.69 (1.03-2.78), and 3.54 (2.01-6.22), respectively. Among individual stressful life events, the following were independently related to MI: death of a close family member, 2.21 (1.01-4.84); death of a close friend, 42.20 (3.70-481.29); major financial problems, 8.94 (1.83-43.63); minor financial problems, 4.74 (2.02-11.14); changes in working hours, 4.99 (1.64-15.22); and changes in working conditions, 30.94 (5.43-176.31).

Conclusions: During this political transition period , stress at work, financial stress, and stress in general as they impacted the population of Belgrade, Serbia were strongly associated with occurence of MI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884755PMC
http://dx.doi.org/10.6515/acs20150424kDOI Listing
May 2016

Comparison of Early Versus Delayed Oral β Blockers in Acute Coronary Syndromes and Effect on Outcomes.

Am J Cardiol 2016 Mar 13;117(5):760-7. Epub 2015 Dec 13.

Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1016/j.amjcard.2015.11.059DOI Listing
March 2016

Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry.

Eur Heart J Qual Care Clin Outcomes 2016 Jan;2(1):45-51

Department of Experimental, Diagnostic and Specialty Medicine , University of Bologna , Via Massarenti 9 , Bologna40138 , Italy.

Aims: Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe.

Methods And Results: Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis ( n = 1032) or underwent primary percutaneous coronary intervention (p-PCI; n = 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07-1.56), age (OR 1.02; CI 1.01-1.03), prior MI (OR 1.79; CI 1.38-2.32), prior cerebrovascular events (OR 1.87; CI 1.30-2.68), chronic kidney disease (OR 1.76; CI 1.22-2.53), Killip class >1 (OR 1.31; CI 1.06-1.62), and time to admission >12 h (OR 15.9; CI 13.1-19.3).

Conclusions: A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission >12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.
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http://dx.doi.org/10.1093/ehjqcco/qcv025DOI Listing
January 2016

Unfractionated heparin-clopidogrel combination in ST-elevation myocardial infarction not receiving reperfusion therapy.

Atherosclerosis 2015 Jul 27;241(1):151-6. Epub 2015 Apr 27.

Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, CiberObn-Institute Carlos III, Autonomous University of Barcelona, Spain.

Objective: We sought explore the relative benefits of unfractionated heparin (UFH) compared with enoxaparin, alone or in combination with clopidogrel, in ST-segment elevation myocardial infarction (STEMI) patients not undergoing reperfusion therapy.

Methods: This is a propensity score study from The International Survey on Acute Coronary Syndromes in Transition Countries (ISACS-TC/NCT01218776) on patients admitted between October 2010-June 2013. There were a total of 1175 STEMI patients who did not receive mechanical or pharmacological reperfusion. Of these, 1063 were eligible for the aim of the study, being treated with UFH (522/1175; 44.4%) or enoxaparin (541/1175; 46%). Clopidogrel in combination with UFH or enoxaparin was given to 751 (63.9%) patients. The primary endpoint was in-hospital mortality. Secondary endpoints were intracranial hemorrhages, and clinically relevant bleedings.

Results: After adjustment for any confounders, UFH was associated with a lower risk of in-hospital mortality in clopidogrel users (multivariate adjusted regression analysis: odds ratio [OR]: 0.62, 95% Confidence Interval [CI] 0.41-0.94) as compared with clopidogrel non-users (OR: 0.94, 95% CI 0.55-1.60). The observed effect was not associated with combined enoxaparin and clopidogrel therapy. Major bleeding events were comparable in the enoxaparin group and UFH group (0.4% and 1.5% respectively, p = 0.06). The risk of major hemorrhage was nearly similar with combined UFH-clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), p = 0.67.

Conclusion: UFH - Clopidogrel combination was associated with a large mortality reduction in STEMI patients not undergoing reperfusion therapy and did not significantly increase the risk of major bleeding.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.04.794DOI Listing
July 2015

Risks for first nonfatal myocardial infarction in Belgrade.

Coll Antropol 2013 Jun;37(2):499-505

Belgrade University, School of Medicine, Institute of Epidemiology, Belgrade, Serbia.

The aim of this study was to investigate which one among possible risk factors are independently related to first nonfatal myocardial infarction (MI) in Belgrade population. Case-control study was conducted in Belgrade during the period 2005-2006. Case group comprised 100 subjects 35-80 years old who were hospitalized because of first nonfatal MI at the coronary care unit in Urgent Center, Belgrade. Control group consisted of 100 persons chosen among patients treated during the same period at the Institute of Rheumatology, Institute for Gastroenterology, and Clinic for Orthopedics, Belgrade, Serbia. Cases and controls were individually matched by sex, age (+/- 2 years) and place of residence (urban/rural communities of Belgrade). According to the multivariate analysis risk factors for MI occurrence were "good" socioeconomic conditions (OR = 2.76), total alcohol consumption (OR = 2.62) and consumption of brandy (OR = 6.73), stressful life events taken together (OR = 3.13) and stress because of close relative Ns death (OR = 3.35), great financial problems (OR = 31.64) and small financial problems (OR = 8.47), hypertension (OR = 2.39), MI among all relatives (OR = 3.66), MI in father (OR = 6.24), and low level of high density lipoprotein cholesterol (OR = 152.41). Amateur sport activity in the past was negatively associated with MI development. The results obtained are mainly in accordance with other studies results and can be of help in development of strategy for coronary heart disease prevention in Serbia.
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June 2013

Exploring in-hospital death from myocardial infarction in Eastern Europe: from the International Registry of Acute Coronary Syndromes in Transitional Countries (ISACS-TC); on the Behalf of the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology.

Curr Vasc Pharmacol 2014 ;12(6):903-9

Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, University of Bologna. Via Massarenti 9 (Padiglione 11), 40138 Bologna, Italy.

Introduction: The aim of the current study was to investigate the outcomes of coronary reperfusion therapies and ST-segment elevation myocardial infarction (STEMI) in patients of Eastern countries with economies in transition. Federation, and Serbia. The overall population consisted of 23,486 consecutive patients admitted to hospitals from January 1(st) to December 31(st) 2009. Registry data and statistics from the Organization for Economic Cooperation and Development (OECD) countries for the same period were used for comparison (2009-2010). In-hospital mortality was between 4% and 5% in the Western countries. In comparison mortality data were significantly larger in Serbia (10.8%) and Bosnia and Herzegovina (11.2%), intermediate in Russian Federation (7.2%) and similar in Hungary (5.0%). The rates of primary percutaneous coronary intervention (primary PCI) were very low in Bosnia and Herzegovina (18.3%), low in Russian Federation (20.6%) and Serbia (22%), and high in Hungary (70%). Major risk factors for death appear to be lack of reperfusion therapy, longer time delay from symptoms onset to hospital presentation as well as the higher percentage of patients with clinical presentation in Killip class III/IV.

Conclusion: In-hospital STEMI case-fatality rates ranges widely in the former Eastern Bloc countries. Beyond the quality of care provided in hospitals, differences in time delay from symptoms onset to hospital admission may strongly influence STEMI patients' outcome.
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http://dx.doi.org/10.2174/157016111206141210122150DOI Listing
August 2015

Utility of lipoprotein-associated phospholipase A2 for prediction of 30-day major adverse coronary event in patients with the first anterior ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

Clin Lab 2012 ;58(11-12):1135-44

Center for Medical Biochemistry, School of Pharmacy, University of Belgrade, Clinical Center of Serbia, Belgrade, Serbia.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested as an inflammatory marker of cardiovascular risk. The predictive value of Lp-PLA2 in ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) has not been established. The aim of this study was to determine whether plasma Lp-PLA2 is a predictor of a major adverse cardiac event (MACE) in patients with the first anterior STEMI treated by primary PCI.

Methods: This study consisted of 100 consecutive patients with first anterior STEMI who underwent primary PCI within 6 hours of the symptom onset. Plasma Lp-PLA2 level was measured on admission using a turbidimetric immunoassay (diaDexus, Inc., USA). The Receiver Operating Characteristic analysis was performed to identify the most useful Lp-PLA2 cut-off level for the prediction of MACE. The patients were divided into two groups according to the cut-off Lp-PLA2 level: high Lp-PLA2 group (> or = 463 ng/mL, n = 33) and low Lp-PLA2 group (< 463 ng/mL, n = 67). MACE was defined as cardiac death, non-fatal reinfarction, and target vessel revascularization.

Results: Patients in the high Lp-PLA2 group had significantly higher total-, LDL-cholesterol, apolipoprotein B levels, and significantly lower estimated glomerular filtration rates compared with the low Lp-PLA2 group. The incidence of 30-day mortality was 18.2% (6/33) in high Lp-PLA2 group, while in the low Lp-PLA2 group no patient died (p < 0.001). The 30-day MACE occurred in 24.2% of the high Lp-PLA2 group and 3% of the low Lp-PLA2 group (p = 0.001). Multiple logistic regression analysis identified the plasma Lp-PLA2 level as an independent predictor of MACE (OR 1.011, 95%CI 1.001 - 1.013, p = 0.037).

Conclusions: In patients with first anterior STEMI treated by primary PCI, the plasma Lp-PLA2 level is an independent predictor of 30-day MACE.
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February 2013

Impact of high post-loading platelet aggregation on 30-day clinical outcomes after primary percutaneous coronary intervention. The antiplatelet regimen tailoring after primary PCI (ART-PCI) trial.

Int J Cardiol 2013 Aug 22;167(4):1632-7. Epub 2012 May 22.

University of Belgrade School of Medicine, Belgrade, Serbia.

Background: Patients with high post-loading platelet aggregation (PPA) are at increased risk of stent thrombosis and death after primary percutaneous coronary intervention (pPCI). The objective of the present trial was to examine whether high PPA is associated with adverse clinical outcomes in pPCI patients whose therapy was modified in accordance with PPA.

Methods: We analyzed 961 consecutive pPCI patients who underwent pPCI between February 2008 and June 2011. High PPA was defined as PPA >50%, 24h after the loading dose. Patients with high PPA were treated with aspirin 300 mg, clopidogrel 150 mg or ticlopidine 500 mg for 30 days. The co-primary efficacy and safety end points at 30 days were major adverse cardiovascular events (MACE) and major bleeding.

Results: We detected high PPA to clopidogrel and aspirin in 44.4% and 16.5% of patients, respectively. The rates of 30-day MACE (adjusted OR 1.76, 95% CI 1.05-2.97), definite subacute stent thrombosis (DSST, adjusted OR 2.15, 95% CI 1.09-4.22) and nonfatal infarction (adjusted OR 3.99, 95% CI 1.57-10.13) were higher in patients with high PPA to clopidogrel compared with responders. High PPA to aspirin was not associated with an adverse 30-day clinical outcome. Compared with high PPA patients who were not tailored, a significantly better outcome with respect to the primary end point was observed in the tailored group (OR 0.42, 95% CI 0.19-0.93).

Conclusion: High PPA to clopidogrel was an independent predictor of 30-day adverse events after pPCI. Among high PPA patients, tailoring was associated with an improved primary outcome.
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http://dx.doi.org/10.1016/j.ijcard.2012.04.129DOI Listing
August 2013

B-type natriuretic peptide predicts new-onset atrial fibrillation in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

Peptides 2012 May 6;35(1):74-7. Epub 2012 Mar 6.

Cardiology Clinic, Clinical Center of Serbia, School of Medicine University of Belgrade, Belgrade, Serbia.

The predictive value of B-type natriuretic peptide (BNP) with respect to the occurrence of new-onset atrial fibrillation (AF) in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is unknown. The aim of this study was to evaluate whether BNP has a predictive value for the occurrence of new-onset AF in patients with STEMI treated by primary PCI. In 180 patients with STEMI treated by primary PCI, BNP concentrations were measured 24h after chest pain onset. The Receiver Operating Characteristic analysis was performed to identify the most useful BNP cut-off level for the prediction of AF. The patients were divided into the two groups according to calculated cut-off level: high BNP group (BNP≥720 pg/mL, n=33) and low BNP group (BNP<720 pg/mL, n=147). The incidence of AF was 5.0%, and occurred more frequently in high BNP group (7/33, 21.2%) than in low BNP group (2/147, 1.4%), (p<0.001). Patients with high BNP were older (p=0.017), had more often anterior wall infarction (p=0.015), higher Killip class on admission (p=0.038), higher peak troponin I (p=0.002), lower left ventricular ejection fraction (p=0.029) than patients with low BNP. After multivariate adjustment, BNP was an independent predictor of AF (OR 3.70, 95% CI 1.40-9.77, p=0.008). BNP independently predicts the occurrence of new-onset AF in STEMI patients treated by primary PCI.
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http://dx.doi.org/10.1016/j.peptides.2012.02.022DOI Listing
May 2012
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