N Kostić’s research while affiliated with University of Belgrade and other places

Background It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. Material/Methods Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. Results Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (p<0.001), and during the interventional phase it dropped from 8.5±1.2% to 7.7±0.7% (p<0.001). BDI-II scores improved significantly from 30.4±13.2 to 23.5±11.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R²=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. Conclusions Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status.

To our knowledge there are no data about the relationship between elevated risk for developing type 2 diabetes mellitus (DM2) and altered cardiac autonomic function. The aim of this study was to evaluate the association between heart rate variability (HRV) and slightly increased risk for DM2. We evaluated 69 subjects (50.0 ± 14.4 years; 30 male) without DM2, coronary artery disease and arrhythmias. The subjects were divided into two groups according to the Finnish Diabetes Risk Score (FINDRISC): group I (n = 39) included subjects with 12 > FINDRISC ≥ 7; group II (n = 30) subjects with FINDRISC < 7. HRV was derived from 24-h electrocardiogram. We used time domain variables and frequency domain analysis performed over the entire 24-h period, during the day (06-22 h) and overnight (22-06 h). Standard deviation of the average normal RR intervals was significantly lower in the group with increased risk for DM2 compared to the group II (127.1 ± 26.6 ms vs 149.6 ± 57.6 ms; p = 0.035). Other time domain measures were similar in both groups. The group I demonstrated significantly reduced frequency domain measures, total power--TP (7.2 ± 0.3 ln/ms2 vs 7.3 ± 0.3 ln/ms2; p = 0.029), and low frequency--LF (5.9 ± 0.4 ln/ms2 vs 6.3 ± 0.6 In/ms2; p = 0.006), over entire 24 h, as well as TP (7.1 ± 0.3 In/ms2 vs 7.3 ± 0.3 In/ms2; p = 0.004), very low frequency (6.2 ± 0.2 In/ms2 vs 6.3 ± 0.2 In/ms2; p = 0.030), LF (5.9 ± 0.4 In/ms2 vs 6.2 ± 0.3 In/ms2; p = 0.000) and high frequency (5.7 ± 0.4 In/ms2 vs 5.9 ± 0.4 In/ms2; p = 0.011) during the daytime compared to the group II. Nocturnal frequency domain analysis was similar between the groups. The low diurnal frequency was independently related to elevated risk for diabetes mellitus (beta = -0,331; p = 0.006). The obtained results suggest that even slightly elevated risk for developing diabetes mellitus may be related to impaired HRV.

To evaluate phasic function and deformation of the left atrium (LA) and right atrium (RA) in subjects with prediabetes and type 2 diabetes mellitus. This cross-sectional study included 50 untreated normotensive subjects with prediabetes, 60 recently diagnosed normotensive diabetic patients and 60 healthy controls of similar sex and age. All the subjects underwent laboratory analyses and complete echocardiographic examination including strain analysis. LA and RA reservoir and conduit function gradually decreased, while booster pump increased, from the healthy controls, throughout the prediabetics, to the diabetics. The strain analysis of atrial phasic function showed more regular pattern of progressive atrial function deterioration than conventional evaluation with total, active and passive atrial function. In the whole study population HbA1c correlated with LA passive emptying fraction (r = -0.38, p < 0.01), LA active emptying fraction (r = 0.36, p < 0.01), LA longitudinal strain during systole (r = -0.35, p < 0.01), RA passive emptying fraction (r = -0.42, p < 0.01), RA active emptying fraction (r = 0.38, p < 0.01), and RA longitudinal strain during systole (r = -0.32, p < 0.01). However, only LA passive emptying fraction (β = -0.32, p < 0.01) and LA longitudinal strain during systole (β = -0.28, p = 0.02) were independently associated with HbA1c among the LA parameters; whereas solely RA passive emptying fraction (β = -0.37, p < 0.01) and RA active emptying fraction (β = 0.31, p = 0.01) were independently associated with HbA1c among the RA parameters. LA and RA phasic functions are significantly impaired in the prediabetics and the diabetics. The parameter of glucose control correlated with LA and RA reservoir, conduit and pump atrial function.

Context: Subclinical hypothyroidism (SHT) is associated with left ventricular (LV) remodeling. The LV mechanics has not been previously assessed by two- and three-dimensional (2DE and 3DE) speckle tracking imaging in the SHT patients. Objectives: The objective of the study was to investigate LV mechanics by 2DE and 3DE speckle tracking in the SHT patients and evaluate the influence of levothyroxine therapy on LV remodeling. Design: We conducted a prospective study. All SHT patients received levothyroxine therapy and were followed up for 1 year after the euthyroid state had been achieved. Setting: The study was performed at a university hospital. Patients: We included 54 untreated women with SHT and 40 healthy control women who were of similar age. Main outcome measures: The 2DE strain and strain rates, 3DE volumes, 3DE strain, and thyroid hormones levels were assessed. Results: The 2DE LV longitudinal and circumferential strain and systolic and early diastolic strain rates were significantly decreased in the SHT patients before therapy in comparison with the controls or the SHT patients after therapy. The 3DE LV cardiac output and ejection fraction were significantly reduced in the SHT patients at baseline compared with the controls or patients after 1 year of treatment. The 3DE LV longitudinal and radial strains were significantly lower in the SHT group before treatment in comparison with the controls or patients after therapy, whereas the 3DE LV circumferential and area strains gradually increased from untreated SHT patients, among the treated SHT patients, to the controls. Conclusion: SHT significantly affects LV deformation assessed by 2DE and 3DE speckle tracking. The improvement of LV mechanics after 1 year of levothyroxine treatment is significant but incomplete.

We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy. To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy. High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%. Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve. Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators.

Metabolic syndrome (MS) is a clustering of cardiovascular risk factors responsible for the development of target organ damage. The aim of this study was to determine the effect of the increasing number of MS risk factors on left ventricular function assessed by noninvasive methods. The study included 204 subjects with MS and 76 controls with no MS risk factors. MS was defined by the presence of 3 or more of ATP-NCEP III criteria. MS subjects were grouped according to the number of criteria they fulfilled: 3 criteria (n=91), 4 criteria (n=65) and 5 criteria (n=48). All subjects underwent laboratory blood tests, complete 2-dimensional, pulse and tissue Doppler echocardiography. Echocardiography was used to assess systolic (LVEF, sseptal), diastolic function, by pulse-wave Doppler (E/A ratio) and tissue Doppler imaging (E/e'average), and global left ventricular function (Tei index). Appropriate time intervals for the estimation of the Tei index were obtained by tissue Doppler. Transmitral E/A ratio decreased significantly and progressively from the 3 criteria to the 5 criteria group (0.82 ± 0.25 vs. 0.79 ± 0.24 vs. 0.67 ± 0.14, p<0.001). The transmitral E/E'average ratio was significantly and gradually increased from the 3 criteria to the 5 criteria group (7.76 ± 1.81 vs. 9.44 ± 2.35 vs. 10.82 ± 2.56, p<0.001). The left ventricle Tei index progressively increased from the 3 criteria to the 5 criteria group (0.43 ± 0.11 vs. 0.48 ± 0.10 vs. 0.54 ± 0.12, p<0.001). The increasing number of MS criteria is associated with cardiac diastolic dysfunction.

Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and diastolic dysfunction after acute myocardial infarction over the long term. Echocardiography was performed within the first week of hospitalization, after one, three and six months in 77 patients with first acute myocardial infarction. At the end of the study the patients were divided into group A and B with mild and severe left ventricular remodeling, respectively. Myocardial performance index was significantly lower in group A compared to B, at the beginning (0.62 vs. 0.75; p = 0.002), and at the end of study (0, 60 vs. 0, 69; p = 0.004). After six months, 31% of study patients developed LV systolic dysfunction with prevalence in group B (56% vs. 19%, p = 0.002). Myocardial performance index > or = 0.70 at first week after acute myocardial infarction is a strong predictive parameter for extensive early and late left ventricular remodeling and systolic dysfunction (p < 0.05), but it is not a valuable predictor of diastolic failure. MPI obtained at first week of acute myocardial infarction was predictive for early and long term left ventricular remodeling and systolic dysfunction. Myocardial performance index had doubtful clinical use in assessing dynamics of remodeling and it was without clinical value in predicting diastolic function deterioration.

Introduction: The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective: The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods: The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (GO), insulin (10) and lipid panel measurements (TC, HDL, LDL, TG) were taken after a 12-hour fasting. Results: The protocol encompassed 40 patients (19 men and 21 women) treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis), Group B (18 patients, 45%, with a single-vessel disease) and Group C (16 patients, 40%, with multi-vessel disease). Presence of lower insulin sensitivity, higher 10 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F = 4.279, p = 0.023, A vs. C p = 0.012, B vs. C p = 0.038; 10: F = 3.461 p = 0.042, A vs. B p = 0.045, A vs. C p = 0.013; TC: F = 2.572, p = 0.09), while no significant difference was found for GO, LDL, HDL and TG. Conclusion: Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

Introduction. Antioxidant systems are important factors affecting the oxidation of lipoproteins and thereby the progression of atherosclerotic disease. It has been suggested that physical activity might maintain and promote the antioxidant defence capacity against the oxidative stress. Left ventricular dysfunction (LVDD) and hypertension are more common in subjects with diabetes mellitus (DM) type 2. Objective. To evaluate the oxidative stress in patients with DM type 2, particularly with LVDD and hypertension and to determine the influence of acute exercise training on the investigated parameters. Methods. To assess the oxidative stress of patients, we determined the following antioxidative parameters: triglycerides (TG), total cholesterol, low density cholesterol, OxLDL cholesterol, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), plasminogen activator-type 1 (PAI-1) which were measured at rest and immediately after the acute bout of the cardiopulmonary exercise cycle ergometer test. Results. In basal conditions, diabetic patients had a significant increase of TG (3.12?1.09 vs 1.74?0.9 mmol/l; p