Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Galectin-3 in Acute Myocardial Infarction Patients with Atrial Fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is common in acute myocardial infarction (AMI), and galectin-3 is possibly involved in its occurrence. Galectin-3 has been shown to play a central role in fibrosis and tissue remodeling and has a role in inflammatory and proliferative responses. The aim of our study was to measure galectin-3 levels in patients with myocardial infarction and to compare its levels in patients with or without AF, in order to investigate the potential predictive role of galectin-3 in this setting. SUBJECTS AND METHODS: The study included 51 consecutive AMI patients with AF; 27 AMI patients (52.9%) had permanent/persistent AF, and 24 patients (47.1%) had paroxysmal AF. Thirty-eight consecutive AMI patients without AF were used as a control group. Blood samples were obtained from venous blood on the third day after reperfusion. RESULTS: Patients with AF had higher levels of C-reactive protein (p < 0.01) and galectin-3 (p < 0.05) than those without AF. Patients with high galectin-3 had 4.4 times greater odds of having AF. Galectin-3 levels were lower in patients without AF (p < 0.01) than in those with permanent/persistent AF. CONCLUSION: AMI patients with AF had higher levels of galectin-3 than those without this arrhythmia. This biomarker of inflammation and fibrosis could be a potential target for treating AMI patients at high risk.

Potential New Approaches in Predicting Adverse Cardiac Events One Month after Major Vascular Surgery.

OBJECTIVE: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. SUBJECTS AND METHODS: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. RESULTS: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. CONCLUSION: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.

Spontaneous Coronary Artery Dissection in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review of the Literature.

Spontaneous coronary artery dissection (SCAD) is a spontaneous intimal tear of the coronary artery wall. A factor rarely associated with SCAD is autosomal dominant polycystic kidney disease (ADPKD). Using the PRISMA guidelines, we identified 10 unique cases of SCAD in ADPKD patients reported between 1998 and 2021. Ages ranged from 36 to 59 years, with an average of 44.6 years. The majority of patients were female (80%). Each case was diagnosed with a cardiovascular event: ST-elevation myocardial infarction (STEMI) in 40%, non-ST elevation myocardial infarction (NSTEMI) in 50%, and stable angina in 10%. Conservative management was used in 60% of cases. There is a significant gap in our understanding of the relationship between SCAD and ADPKD. Polycystin complex can lead to structural abnormalities in blood vessels, resulting in vascular leaks and vessel rupture. This suggests that ADPKD patients may have an elevated risk of arteriopathies, including coronary artery dissection.

Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.

Population pharmacokinetics of bisoprolol in patients with chronic heart failure.

PURPOSE: The aim of the study was to develop a population pharmacokinetic (PK) model for clearance of bisoprolol in patients with congestive heart failure (CHF). METHODS: Parameters associated with the plasma concentrations of bisoprolol at steady-state were analyzed in 61 patients (mean age 66.21 ± 9.49 years; mean total body weight 8.90 ± 12.26 kg) with CHF using non-linear mixed-effect modeling (NONMEM). A validation set of 17 patients with heart failure was used to estimate the predictive performance of the pharmacokinetic model. RESULTS: The typical mean value for bisoprolol clearance (CL), estimated by the base model (without covariates), in our population was 11.4 l h(-1). In the full model, covariates such as bisoprolol total daily dose (DD) and creatinine clearance were included. The final regression model for the clearance of bisoprolol was the following: CL (l h(-1)) = 4.68 + 0.859 * DD. CONCLUSION: The derived PK model describes the clearance of bisoprolol in patients with CHF, showing that the total daily dose of bisoprolol is the most important covariate. This finding will provide the basis for future PK studies on beta blockers in this specific patient population and lead to better overall management of heart failure.

A review of the risk and precipitating factors for spontaneous coronary artery dissection.

Introduction: Spontaneous coronary artery dissection (SCAD) accounts for 1%-4% of cases of acute coronary syndrome (ACS). SCAD is caused by separation occurring within or between any of the three tunics of the coronary artery wall. This leads to intramural hematoma and/or formation of false lumen in the artery, which leads to ischemic changes or infarction of the myocardium. The incidence of SCAD is higher in women than in men, with a ratio of approximately 9:1. It is estimated that SCAD is responsible for 35% of ACS cases in women under the age of 60. The high frequency is particularly observed during pregnancy and in the peripartum period (first week). Traditional risk factors are rare in patients with SCAD, except for hypertension. Patients diagnosed with SCAD have different combinations of risk factors compared with patients who have atherosclerotic changes in their coronary arteries. We presented the most common so-called "non-traditional" risk factors associated with SCAD patients. Risk factors and precipitating disorders which are associated with SCAD: In the literature, there are few diseases frequently associated with SCAD, and they are identified as predisposing factors. The predominant cause is fibromuscular dysplasia, followed by inherited connective tissue disorders, systemic inflammatory diseases, pregnancy, use of sex hormones or steroids, use of cocaine or amphetamines, thyroid disorders, migraine, and tinnitus. In recent years, the genetic predisposition for SCAD is also recognized as a predisposing factor. The precipitating factors are also different in women (emotional stress) compared with those in men (physical stress). Women experiencing SCAD frequently describe symptoms of anxiety and depression. These conditions could increase shear stress on the arterial wall and dissection of the coronary artery wall. Despite the advancement of SCAD, we can find significant differences in the clinical presentation between women and men. Conclusion: When evaluating patients with chest pain or other ACS symptoms who have a low cardiovascular risk, particularly female patients, it is important to consider the possibility of ACS due to SCAD, particularly in conditions often associated with SCAD. This will increase the recognition of SCAD and the timely treatment of affected patients.

Synergistic antibacterial activity of Salvia officinalis and Cichorium intybus extracts and antibiotics.

Synergistic activity of Salvia officinalis and Cichorium intybus extracts and commonly used antibiotics, amoxicillin and chloramphenicol, were evaluated. Interactions between plant extracts and antibiotics were tested by checkerboard method and interpreted as FIC index. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and clinical isolates Staphylococcus aureus, Bacillus subtilis, Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were used. Salvia officinalis showed better synergistic capacity than Cichorium intybus. Synergistic interactions were observed between amoxicillin and acetone or ethyl acetate extract of Salvia officinalis and between chloramphenicol and ethyl acetate extract of Salvia officinalis. In the presence of sub-inhibitory concentration (1/4 MIC to 1/32 MIC) of sage extracts, the MIC values of antibiotics were decreased by 2- to 10-fold. Synergism was observed against all test bacteria, except Escherichia coli. The combinations of acetone and ethyl acetate extract from Cichorium intybus and antibiotics resulted in additive and indifferent effects against tested bacteria.

Association Between Metabolic Syndrome, Its Components, and Knee Osteoarthritis in Premenopausal and Menopausal Women: A Pilot Study.

OBJECTIVE: This pilot study aimed to determine the correlation of metabolic syndrome (MetS), its components, and increased LDL (low-density lipoprotein) and total cholesterol levels with osteoarthritis (OA). In addition, our goal was to establish the association between MetS and the degree of handicap measured by the Lequesne index of functionality and severity of knee osteoarthritis. MATERIALS AND METHODS: The pilot study included 25 subjects with knee OA and 19 subjects without knee OA. All subjects were menopausal or premenopausal women. MetS was diagnosed according to the National Cholesterol Education Program, Adult Treatment Panel III. OA was diagnosed if Kellgren-Lawrence ≥ 2. RESULTS: MetS was detected in 80% of subjects with OA. In the non-OA group, MetS was detected in 26% of subjects. The difference in MetS prevalence between the two groups was significant (p=0.000). The presence of each MetS component was significant in the OA group, except for central obesity, which presence was marginally significant (p=0.054). Prevalence of increased total (p=0.019) and LDL cholesterol (p=0.000) was also significant in the OA group. A significant difference between OA and the non-OA group was detected in the prevalence of all five MetS components (p=0.016). In the OA group, the Lequesne index of functionality and severity of knee osteoarthritis was not significantly altered between subjects with and without MetS. CONCLUSION: Metabolic syndrome, its components, increased LDL, and total cholesterol are correlated with osteoarthritis in premenopausal and menopausal women. MetS is not correlated with the degree of handicap in the knee joint measured by the Lequesne index.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Prognostic significance of microalbuminuria in patients with acute myocardial infarction.

BACKGROUND: Microalbuminuria has been reported to occur in patients with acute myocardial infarction (AMI) and associated with worse outcome. In our prospective analysis we included patients with AMI with the primary aim to examine whether urinary albumin excretion is increased in those patients and whether it is associated with worse in-hospital prognosis (major complications). The secondary objective was to examine the predictive power of microalbuminuria for 6-month mortality and re-hospitalization for cardiovascular disease. METHODS: One hundred thirty patients admitted to the Coronary Care Unit were studied prospectively. The diagnosis of myocardial infarction was based on the latest criteria of the European Cardiac Society. Microalbuminuria was defined as a urinary albumin creatinine ratio (UACR) and was measured on the third day after admission in the first morning urine sample. RESULTS: One hundred thirty patients were enrolled in this study--82 (63.03%) men and 48 (36.92%) women, age 62.48 +/- 12 years. A high proportion of study patients (27.7%) had microalbuminuria and 8.5% had overt albuminuria (UACR over 25 mg/mmol in men and over 35 mg/mmol in women) at the time of urine examination. During the hospital stay (average 7.6 +/- 3.0 days) 4 patients (3.1%) died from cardiovascular complications and all had microalbuminuria. In our study a high percentage of patients with in-hospital nonfatal complications had microalbuminuria but it did not have positive predictive association with the occurrence. During a 6-month follow-up period, 8 patients died from cardiovascular cause. In-hospital and total mortality (in-hospital and the during six-month follow-up) were significantly frequent in patients with microalbuminuria (p < 0.05). During a six-month follow-up period, 24 patients (18.5%) were re-hospitalized for cardiovascular disease and, among them, 54.2% had microalbuminuria. In univariant regression analysis microalbuminuria increased the risk for re-hospitalization, but multiple analysis didn't show the significance. CONCLUSIONS: We found that UACR measured during the first week after AMI is independently associated with increased long-term risk for in-hospital and six-month mortality. On the basis of these results, we suggest that this measurement should be included in the routine clinical work up of patients with AMI.

Preoperative Levels of the Soluble Urokinase-Type Plasminogen Activator Receptor as Predictor for New Episodes of Atrial Fibrillation After Vascular Surgery.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) in uPAR soluble form is produced when the uPAR is cleaved from the cell membrane during the inflammatory process. Postoperative atrial fibrillation (AF) is the most common perioperative cardiac arrhythmia. It is speculated that elevated suPAR has a role in the development of AF. The aim of our study was to investigate the predictive role of preoperative suPAR in the occurrence of AF during the first 6 months after major vascular surgery. METHODS: We included 119 male and 63 female patients with an average age of 67.19 ± 6.02 years, without permanent/persistent AF. Basic predictive model (BASIC) included traditional risk factors for AF: age, gender, body mass index-BMI, smoking status, presence of arterial hypertension, diabetes mellitus and dyslipidemia. RESULTS: Over the 6-month period, 19 (10.4%) patients had one new episode of atrial fibrillation and 2 patients (1.1%) had 2 episodes of paroxysmal atrial fibrillation. Paroxysms of AF were significantly more frequent in patients who had a resection of an abdominal aneurysm than in patients with other types of major vascular surgery. BASIC had good discriminatory ability in the prediction of AF paroxysms during the first 6 months after surgery (AUC = 0.715, 95%CI 0.590-0.840). Adding suPAR to the basic model significantly improved the discriminative ability of the predictive model for AF episodes (ΔAUC = 0.238, p < 0.001). The predictive performance of the model BASIC+CRP+suPAR, measured using AUC, NRI and IDI statistics, was very similar to the model BASIC+suPAR. CONCLUSION: AF is a common complication in surgical patients with high mortality and morbidity. suPAR could improve the ability of traditional risk factors to predict its occurrence up to 6 months after major vascular surgery.

Design and development of novel therapeutics for coronary heart disease treatment based on cholesteryl ester transfer protein inhibition - in silico approach.

Cholesteryl ester transfer protein (CETP) belongs to the group of enzymes which inhibition have the application in the treatment of cardiovascular diseases. This study presents QSAR modeling for a set of compounds acting as CETP inhibitors based on the Monte Carlo optimization with SMILES notation and molecular graph-based descriptors, and field-based 3D modeling. A 3D QSAR model was developed for one random split into the training and test sets, whereas conformation independent QSAR models were developed for three random splits, with the results suggesting there is an excellent correlation between them. Various statistical approaches were used to assess the statistical quality of the developed models, including robustness and predictability, and the obtained results were very good. This study used a novel statistical metric known as the index of ideality of correlation for the final assessment of the model, and the results that were obtained suggested that the model was good. Also, molecular fragments which account for the increases and/or decreases of a studied activity were defined and then used for the computer-aided design of new compounds as potential CETP inhibitors. The final assessment of the developed QSAR model and designed inhibitors was done using molecular docking, which revealed an excellent correlation with the results from QSAR modeling.Communicated by Ramaswamy H. Sarma.

Sex-related difference in the prognostic value of syncope for 30-day mortality among hospitalized pulmonary embolism patients.

INTRODUCTION: Recent studies report that syncope is not a significant predictor of 30-day mortality in pulmonary embolism (PE) patients, yet some data suggest sex-related differences may be relevant. OBJECTIVES: To evaluate sex-specific prediction significance of syncope for 30-day mortality in PE patients. METHODS: A multicentric, retrospective, observational, registry-based study on consecutive PE patients was undertaken. Patients were allocated into either a men or a women group before comparisons were made between patients with syncope and those without syncope. A sex-related prediction of the significance of syncope for 30-day mortality was evaluated. RESULTS: Overall 588 patients [294 (50%) men and 294 (50%) women] were included within the study. Among men, patients with syncope were older and had significantly higher parameters of increased 30-day mortality then patients without syncope. Within the same group, however, difference in the 30-day mortality rate was not significant (log rank P = .942). In contrast to the men, fewer differences in admission characteristics were noticed among women, but those with syncope had significantly increased signs of the right ventricular dysfunction and increased 30-day mortality rate, as compared with those without syncope (log rank P = .025). After adjustment for age in a Cox regression analysis, syncope was a significant predictor of 30-day mortality in women (HR = 2.01, 95%CI 1.02-3.95). CONCLUSION: Although syncope is associated with other predictors of higher early mortality in both male and female PE patients, only in women it is a significant predictor of 30-day mortality.

Renal dysfunction as intrahospital prognostic indicator in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients. METHODS: The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events. RESULTS: Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30-60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243-11.911, p < 0.001; HR 2.554, 95% CI 1.598-4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups. CONCLUSION: Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality.

Development and design of novel cardiovascular therapeutics based on Rho kinase inhibition-In silico approach.

Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set. Molecular descriptors used for QSAR modeling were based on the SMILES notation and local invariants of the molecular graph. The statistical quality of the developed model, including robustness and predictability, was tested with different statistical approaches and satisfying results were obtained. The best calculated QSAR model had the following statistical parameters: r2 = 0.8825 and q2 = 0.8626 for the training set and r2 = 0.9377 and q2 = 0.9124 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for the final model assessment, and the obtained results were 0.6631 for the training and 0.9683 for the test set. Molecular fragments responsible for the increases and decreases of the studied activity were defined and they were further used for the computer-aided design of new compounds as potential Rho kinase inhibitors. The final assessment of the developed QSAR model and designed inhibitors was achieved with the application of molecular docking. An excellent correlation between the results from QSAR and molecular docking studies was obtained.

The impact of police presence on angry and aggressive driving.

An extensive body of research has found that angry and aggressive driving are both significantly related to crash involvement. There has also been a large body of research investigating the situational factors related to angry and aggressive driving, but one interesting question that has not yet been answered is whether the enforcement of traffic laws causes or reduces angry and aggressive driving. The independent region of Northern Kosovo represents a unique opportunity to investigate the impact of a lack of traffic enforcement on driving behaviour. Therefore, the present study set out to investigate whether the presence of traffic enforcement has a significant impact on the level of driver anger and aggressive driving. Registered owners of motor vehicles in Northern Kosovo and Serbia were both sent a questionnaire which contained the 28-item Dula Dangerous Driving Index (DDDI) and the 21-item UK Driving Anger Scale (UKDAS). This found that anger was higher in two of the four driving anger factors (direct hostility and progress impeded) and two of the three DDDI factors (risky driving & aggressive driving). Furthermore, the present study found that the lack of police enforcement was a significant predictor of both aggressive and risky driving, even after the driving anger and demographic variables had been partialled out. Therefore, it appears that introducing or increasing traffic enforcement may be one method of reducing aggressive and risky driving behaviour.

A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.

Erectile dysfunction as a predictor of two-year prognosis in acute myocardial infarction.

BACKGROUND: Erectile dysfunction (ED) is a predictor or marker of coronary artery disease in patients at high risk of cardiovascular diseases. The aim of this study was to investigate the prevalence of ED in patients with acute myocardial infarction (AMI) and after 2 years of follow-up, and to determine the association between ED and the concentrations of the markers of inflammation, endothelial dysfunction and oxidative stress which were measured on the third day after hospital admission. METHODS: The study included 80 patients aged 62.25 ± 10.47 years. The primary endpoints of interest were re-hospitalization due to cardiovascular causes and death during the 2 year period after hospital-ization. The Sexual Health Inventory for Men (SHIM) was assessed at the point of hospital discharge and 24 months thereafter. RESULTS: 40.1% of patients had some degree of ED. The percentage of patients without ED increased (13.2%), while the percentage of patients with severe ED significantly decreased (14.7%) after 2 years. Patients with ED had significantly higher B-type natriuretic peptide (BNP) levels and decreased levels of nitric-oxide. During the 2 years of follow-up, 9 patients died (6.5% without ED, 68.6% with ED) (c2 = 7.19, p = 0.015). During the same time period, 22 (27.5%) patients were re-hospitalized due to cardiovascular causes, of whom 59.1% had ED at hospital admission (p < 0.05). CONCLUSIONS: Low levels of nitric-oxide were the best predictors of ED during AMI and after 2 years. ED predicted the worst outcomes of AMI: death and re-hospitalization. Lifestyle changes and nitric- -oxide donors could assist in the treatment of ED and in the improvement of long-term prognosis for AMI. (Cardiol J 2017; 24, 4: 393-402).

Regional differences in health-related quality of life in elderly heart failure patients: results from the CIBIS-ELD trial.

AIM: Patient-reported outcomes such as health-related quality of life (HRQoL) are main treatment goals for heart failure (HF) and therefore endpoints in multinational therapy trials. However, little is known about country-specific differences in HRQoL and in treatment-associated HRQoL improvement. The present work sought to examine those questions. METHODS AND RESULTS: We analysed data from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial, in which patients from central and south-eastern Europe completed the HRQoL questionnaire SF-36 at baseline and the end of a 12-week beta-blocker up-titration (follow-up). 416 patients from Serbia (mean age 72.21 years, 69% NYHA-class I-II, 27.4% women) and 114 from Germany (mean age 73.64 years, 78.9% NYHA-class I-II, 47.4% women) were included. Controlling for clinical variables, the change in mental HRQoL from baseline to follow-up was modulated by Country: Serbian patients, M baseline = 37.85 vs. M follow-up = 40.99, t(526) = 5.34, p < .001, reported a stronger increase than Germans, M baseline = 37.66 vs. M follow-up = 38.23, t(526) = 0.68, ns. For physical HRQoL, we observed a main effect of Country, M Serbia = 39.28 vs. M Germany = 35.29, t(526) = 4.24, p < .001. CONCLUSION: We observed significant differences in HF patients from Germany and Serbia and country-specific differences between Serbian and German patients in mean physical HRQoL. Changes in mental HRQoL were modulated by country. Those results may reflect psychological, sociocultural, aetiological differences or regional differences in phenotype prevalence. More importantly, they suggest that future multinational trials should consider such aspects when designing a trial in order to avoid uncertainties aligned to data interpretation and to improve subsequent treatment optimisation.