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Namik Selimović, Amina Marić, A. Šljivo, Aladin Altic, Irma Fajić, Lana Lekić, A. Durak-Nalbantić

<p><strong>Aim</strong> Despite advancements in the diagnosis, treatment and monitoring of patients with acute coronary syndrome (ACS), morbidity and mortality following ACS remain high. The aim of this study was to actively seek possible predictors of adverse outcomes after ACS aiming to identify high-risk patients promptly.<br /><strong>Methods</strong> This retrospective cohort study investigated patients with ACS hospitalized at Clinical Centre of the University of Sarajevo from 2019 to 2021. Patients were followed up for a period of 12 months post-discharge to assess major cardiovascular events (MACE) and MACE associated independent predictors.&nbsp;<br /><strong>Results</strong>. The study included 121 patients, mostly male 102 (84.3%), with a mean age of 60.83&plusmn;12.61 years; prevalent risk factors were hypertension 94 (77.7%), dyslipidaemia 84 (69.4%), diabetes mellitus 91 (75.2%), active smoking 67 (55.4%) and positive family history of cardiovascular diseases 81 (66.9%). MACE occurred in 33 (27.3%) patients since the initial ACS, and those patients were older (p=0.012), had higher level of creatinine (p&lt;0.001), lower ejection fraction at discharge (p&lt;0.001) and larger left atrial diameter (p=0.032). Serum creatinine (OR=1.014, 95% CI 1,003-1,026, p=0.017) and ejection fraction (OR=0.924, 95% CI 0,869-0,984, p=0.013) were independent predictors associated with a 12-month follow up MACE following ACS.<br />Conclusion A monitoring of serum creatinine level, left atrial diameter, and ejection fraction post-acute coronary syndrome as potential indicators of future MACE within a 12-month follow-up period is of great importance. These findings emphasize the need for tailored management strategies to mitigate risks in this patient population.</p>

ntroduction: The thyroid hormone secretion disorders may be hyperthyroidism (reduced TSH levels and increased levels of FT3 and FT4) and subclinical hyperthyroidism (decreased concentration of TSH with normal FT3 and FT4).Aim: To investigate levels of thyroid hormones (TSH, FT3, and FT4) in patients with hyperthyroidism or subclinical hyperthyroidism treated at Tuzla Blue Clinic.Materials and methods:The study included 120 patients divided into three groups: a control group, groups with respondents who have hyperthyroidism, and a group of patients with subclinical hyperthyroidism. The concentrations of the hormones TSH, FT3, and FT4 were analyzed. The determination was carried out on the device IMMULITE 1 Siemens using the immunochemistry method. Results:TSH between our group investigated the existence of significant statistical differences between the control group and the group with hyperthyroidism (p<0.0001) and between the control group and the group withsubclinical hyperthyroidism (p=0.0001), and the parameter FT3 showed that a statistically significant difference exists between the control group and the group with hyperthyroidism (p<0.0001), and between patients with hyperthyroidism andsubclinical hyperthyroidism (p<0.0001). For FT4, we found a statistically significant difference between the control group and the group with hyperthyroidism (p<0.0001) and between groups with hyperthyroidism and subclinical hyperthyroidism (p <0.0001).Conclusions: The concentration of TSH is reduced in both hyperthyroidism and subclinical hyperthyroidism. The serum concentrations of FT3 and FT4 are elevated in hyperthyroidism, while in subclinical hyperthyroidism, the serum concentrations of FT3 and FT4 stand in the reference area.Keywords:Thyrotropin, thyroxine, TSH, FT3, FT4, hyperthyroidism

Shaun G. Goodman, P. Steg, M. Szarek, Deepak L. Bhatt, Vera A Bittner, Rafael Diaz, Robert A Harrington, J. Jukema et al.

Abstract The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

D. Rebić, E. Begić, A. Šljivo, Nermir Granov, Senad Hasanspahić, A. Džubur, A. Durak-Nalbantić

Aim To assess morphological characteristics of carotid blood vessels in uremic patients before to the initiation of the dialysis treatment, and corelate data with various dialysis therapy modules. Methods The study included 30 patients with end-stage renal disease (ERDS) prior to commencing dialysis, 30 patients treated with haemodialysis and 30 patients treated with continuous ambulatory peritoneal dialysis. The control group consisted of 15 subjects with normal kidney function (eGFR>60ml/min). Carotid intima-media thickness (CIMT), as well as lipid status values (cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A, apolipoprotein B) were evaluated. Results The significant difference in CIMT was detected between the control and haemodialysis groups (p<0.001), and between the control and the peritoneal dialysis group (p=0.004). In patients in the predialysis group, CIMT was influenced by cholesterol (p=0.013), HDL (p=0.044), LDL (p=0.001) and ApoB (p=0.042) values. A significant difference in CIMT was proved between the haemodialysis and predialysis group of patients (p<0.001). The only variable from the patient's lipometabolic profile significantly associated with the change in IMT in uremic patients was HDL. A significant difference was found in the average value for systolic blood pressure (p<0.001) and diastolic blood pressure (p=0.018) in patients before starting the dialysis treatment compared to patients treated with other dialysis methods. Conclusion Patients on haemodialysis treatment had a significantly greater CIMT, which is in relation with a higher cardiovascular risk.

A. Durak-Nalbantić, E. Begić, A. Begić, A. Džubur, O. Lepara, R. Baljic, A. Hamzić-Mehmedbašić, D. Rebić et al.

Introduction: Heart failure (HF) still remains as one of the most common causes of hospital admission with a high mortality rate. Aim: To investigate the possible prognostic role of brain natriuretic peptide (BNP), high-sensitivity (hs) cardiac troponin (cTn) I, cystatin C, and cancer antigen 125 (CA125) in the prediction of decompensation after an index hospitalization and to investigate their possible additive prognostic value. Patients and Methods: Two hundred twenty-two patients hospitalized with acute HF were monitored and followed for 18 months. Results: BNP at discharge has the highest sensitivity and specificity in the prediction of decompensation. For a cutoff value of 423.3 pg/ml, sensitivity was 64.3% and specificity was 64.5%, with a positive predictive value of 71.6% and an area under the curve (AUC) of 0.69 (P < 0.001). The hazard risk (HR) for decompensation when the discharge BNP was above the cutoff value was 2.18. Cystatin C, at a cutoff value of 1.46 mg/L, had a sensitivity of 57% and specificity of 57.8%, with a positive predictive value of 65.8% and an AUC of 0.59 (P = 0.028). CA125, in the prediction of decompensation in patients with acute heart failure (AHF) and at a cutoff value of 80.5 IU/L, had a sensitivity of 60.5% and specificity of 53.3%, with a positive predictive value of 64.5% and an AUC of 0.59 (P = 0.022). The time till onset of decompensation was significantly shorter in patients with four versus three elevated biomarkers (P = 0.047), with five versus three elevated biomarkers (P = 0.026), and in patients with four versus two elevated biomarkers (P = 0.026). The HR for decompensation in patients with five positive biomarkers was 3.7 (P = 0.001) and in patients with four positive biomarkers was 2.5 (P = 0.014), compared to patients who had fewer positive biomarkers. Conclusion: BNP, cystatin C, and CA125 are predictors of decompensation, and their combined usage leads to better prediction of new decompensation.

D. Rebić, E. Begić, Buena Aziri, A. Džubur, Ena Gogić, A. Durak-Nalbantić, A. Hamzić-Mehmedbašić, Senad Hasanspahić et al.

Background: To evaluate atherosclerotic changes in carotid arteries (CCA) in uremic patients before and after 18 months of continuous ambulatory peritoneal dialysis (CAPD) treatment, and to evaluate the impact of dyslipidemia and CAPD treatment on vascular remodeling. Materials and Methods: We conducted a longitudinal, prospective study during 2020 and 2021 at the Clinic for Nephrology, Clinical Center University of Sarajevo. Patients with end-stage renal disease were included and were followed during 18 months of CAPD treatment. All patients were treated using commercially prepared biocompatible balanced dialysis solutions. Carotid intima-media thickness (IMT) and atherosclerotic plaques on the common carotid artery (CCA) were measured by echotomography. Results: A total of 50 patients were included and were followed during 18 months of CAPD treatment. Lipid values in the serum of patients with CAPD were significantly lower after 18 months of CAPD treatment compared to the values before treatment, while the value of high-density lipoprotein (HDL) was significantly increased after 18 months of CAPD treatment. The values of IMT and the diameter of the CCA compared to the basal values were significantly lower (P < 0.001). Conclusion: We demonstrated significantly lower lipid values and higher HDL levels following CAPD treatment. Correct selection of the targeted pharmacological intervention can substantially impact the regression of vascular changes in patients on peritoneal dialysis.

E. Ademović, Mirza Čakarić, A. Durak-Nalbantić, A. Džubur, E. Hodžić, Sabina Mahmutović, I. Aganović, M. Dilić et al.

BACKGROUND Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. OBJECTIVE The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. METHODS This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Familly Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. RESULTS Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartScore, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event (r= 0.249, p= 0.000). CONCLUSION High prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of trygliceride measurement.

A. Iglica, E. Begić, N. Šabanović-Bajramović, Buena Aziri, Z. Tafi, Z. Begić, A. Durak-Nalbantić, F. Zukić

N. Naser, A. Durak-Nalbantić, N. Šabanović-Bajramović, Alen Karić

Background: Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines, the prescription of a MRA is recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure and no contraindications for this therapy. Objective: The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function by measuring left ventricle ejection fraction (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF. Methods: From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size and matched by age and gender patients in Spiron-HF group for management of chronic HFrEF. Each patient was evaluated clinically, biochemically, and echocardiographically at the beginning of treatment (baseline) after 6 months and at the end of 12th month. Echocardiography was performed to find out change in left ventricular systolic function. Results: After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P < 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P < 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P < 0.05), occurred after 12 months of treatment. Left ventricular global longitudinal strain (LV GLS) was significantly improved in Epler-HF group compared with Spiron-HF group (0.6 ± 0.4 versus 3.4 ± 0.9; P < 0.05). There were no significant differences observed in reduction of left ventricular end-diastolic volume (2.2 ± 0.5 ml versus 4.7 ± 1.1ml; P =0.103) and left ventricular diastolic diameter (1.2 ± 0.6 versus 1.7 ± 0.3; P=0.082) in both arms. The effects of both MRA agents spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34–0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44–0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73– 1.27; p= 0.675). Conclusion: Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEF.

G. Schwartz, M. Szarek, Deepak L. Bhatt, V. Bittner, M. Bujas‐Bobanovic, R. Díaz, S. Fazio, Z. Fras et al.

Abstract Aims Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Methods and results In 18 924 patients with recent acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score–matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median of 8.3 months from randomization, after a median of 6.0 months with LDL-C <0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than those of the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C vs. 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). Conclusion A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with a lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. Trial registration ClinicalTrials.gov NCT01663402

M. Halilčević, E. Begić, Amela Džubur, A. Džubur, Buena Aziri, A. Durak-Nalbantić, A. Begić, Ammar Brkić et al.

Aim To examine a relation of thyroid function, neutrophil-lymphocyte ratio (NLR) with left ventricular function measured through the left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods This prospective research involved 160 consecutive patients with acute myocardial infarction. Patients were divided into those with normal thyroid hormone status (n=80) and those with hypothyroidism (newly diagnosed) (n=80). Inflammatory parameters and parameters of hormonal status were taken for analysis: thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). All patients underwent transthoracic echocardiographic examination (TTE) five days upon admission, and left ventricular ejection fraction (LVEF) was analysed. Results Significant difference between the two groups was verified in values of T3, T4, erythrocytes, haemoglobin, haematocrit, neutrophil, lymphocytes, NLR, C-reactive protein (CRP) and sedimentation rate. Patients with euthyroidism had a higher frequency of coronary single-vessel disease (p=0.035) and a significantly lower frequency of triple vessel disease (p=0.046), as well as a higher median value of LVEF (p=0.003). There was a significant correlation between LVEF with haemoglobin values (p=0.002), NLR (p=0.001), and CRP (p=001). Conclusion The altered status of the thyroid gland in acute myocardial infarction is associated with the severity of the coronary blood vessel lesion, LVEF and correlates with inflammatory response.

A. Džubur, E. Begić, A. Durak-Nalbantić, Buena Aziri

Cardiomyopathies are diseases of the heart muscle, and present a heterogeneous group of myocardial diseases with mechanical or electrical dysfunction, characterized by ventricular hypertrophy or dilatation. They can be strictly related to the heart muscle (primary), or as part of a systemic disease (secondary), and represent a factor that leads to a reduced quality of life, the occurrence of heart failure and mortality. The primary ones are those that are genetic conditioning, the mixed ones include dilated and restrictive cardiomyopathy, and the acquired ones are caused by myocarditis, stress-induced, peripartum, tachycardia-induced and those caused by endocrine pathology (primarily in newborns of mothers with a diagnosis of diabetes mellitus). Etiologically, they can arise as a result of a genetic mutation, an inflammatory process, and they are also divided into metabolic, toxic and those caused by some other cause. The aim of the article was to present the characteristics of cardiomyopathies themselves in relation to the etiological factor, with review of the diagnostic and therapeutic modality.

E. Begić, A. Iglica, R. Gojak, R. Baljic, Z. Begić, A. Durak-Nalbantić, M. Halilčević, A. Džubur et al.

Aim The aim of this study was to link the values of D-dimer and C-reactive protein (CRP), with the occurrence of pericardial effusion in patients who had coronavirus disease 2019 (COVID-19) and have preserved systolic function of the left ventricle (LV). Methods This was a prospective study and included 146 patients who underwent echocardiographic examination 30 days after the acute phase of COVID-19. Patients who were placed on mechanical ventilation, patients who had pulmonary thromboembolism or acute coronary syndrome during the acute period of the disease, patients who had an ejection fraction of the LV <50%, patients who were diagnosed with pericarditis during acute illness or clinical signs of heart failure (or had elevated N-terminal-pro hormone B-type natriuretic peptide value), with verified renal or hepatic dysfunction were excluded from the study, including patients with diabetes mellitus Type 1, patients with cancer, connective tissue disease, or pregnant women. The existence of cardiovascular risk factors (hypertension, diabetes mellitus Type 2, and hyperlipidemia), the presence of previous ischemic heart disease, maximum values of D-dimer, and CRP (during the first 15 days of the disease) was taken into the analysis. Results Effusion was verified around the right atrium (RA) in 104 patients (3.85 ± 1.75 mm), in 135 patients next to the free wall of the right ventricle (RV) (5.24 ± 2.29 mm), in front of the apex of the LV in 27 patients (2.44 ± 0.97 mm), next to the lateral wall of LV in 35 patients (4.43 ± 3.21 mm), and behind the posterior wall of LV in 30 patients (2.83 ± 1.62 mm). Mean CRP values during the acute phase of the disease were 43.0 mg/L (8.6–76.2 mg/L), whereas D-dimer mean value was 880.00 μg/L (467.00 –2000.00 μg/L). CRP values correlated with effusion next to the free wall of RV (rho = 0.202; P = 0.018). The D dimer correlated with effusion around RA (rho = 0.308; P = 0.0001). Conclusion The clinical picture of the post-COVID patients could be explained by the appearance of pericardial effusion. D-dimer value correlates with the occurrence of effusion around RA, whereas CRP value correlates with effusion next to the free wall of RV.

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