Bosa Mirjanic-Azaric, Novak Vasic, Darko Cerne, Janko Kos and Natasa Bogavac-Stanojevic
Cathepsin S (CTSS) is a cysteine protease involved in atherogenesis. We compared the plasma CTSS as well as other biomarkers of atherosclerosis in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD), aiming to identify the underlying pathogenic mechanisms of the disease development. Also, we hypothesised that the level of plasma CTSS simultaneously increases with a decrease of plasma high-density lipoprotein cholesterol (HDL-C) values.
33 patients with AAA and 34 patients with AOD were included in this study.
There was no difference in the level of plasma CTSS between the two analysed groups (p=0.833). In the patients with AAA, the plasma CTSS was correlated with HDL-C (r = -0.377, p = 0.034) and total bilirubin (r =0.500, p = 0.003) while, unexpectedly, it was not correlated with cystatin C (Cys C) (r =0.083, p = 0.652). In the patients with AOD, the plasma CTSS correlated with triglycerides (r = 0.597, p< 0.001), only. When the patients were divided according to HDL-C (with HDL-C ≤0.90 and HDL-C >0.90 mmol/L), the plasma CTSS values differed among these groups (31.27 vs.25.61 μg/L, respectively, p<0.001).
These results provide the first evidence that CTSS negatively correlated with HDL-C and bilirubin in patients with AAA. It is possible that differences in the association of the CTSS and other markers of atherosclerosis can determine whether atherosclerotic aorta will develop dilatation or stenosis.
Natasa Bogavac-Stanojevic and Zorana Jelic-Ivanovic
Laboratory testing as a part of laboratory in vitro diagnostic (IVD) has become required tool in clinical practice for diagnosing, monitoring and prognosis of diseases, as well as for prediction of treatment response. The number of IVD tests available in laboratory practice has increased over the past decades and is likely to further increase in the future. Consequently, there is growing concern about the overutilization of laboratory tests and rising costs for laboratory testing. It is estimated that IVD accounts for between 1.4 and 2.3% of total healthcare expenditure and less than 5% of total hospital cost (Lewin Group report). These costs are rather low when compared to pharmaceuticals and medical aids which account for 15 and 5%, respectively. On the other hand, IVD tests play an important role in clinical practice, as they influence from 60% to 70% of clinical decision-making. Unfortunately, constant increases in healthcare spending are not directly related to healthcare benefit. Since healthcare resources are limited, health payers are interested whether the benefits of IVD tests are actually worth their cost. Many articles have introduced frameworks to assess the economic value of IVD tests. The most appropriate tool for quantitative assessment of their economic value is cost-effectiveness (CEA) and cost-utility (CUA) analysis. The both analysis determine cost in terms of effectiveness or utilities (combine quantity and quality of life) of new laboratory test against its alternative. On the other hand, some investigators recommended calculation of laboratory test value as product of two ratios: Laboratory test value = (Technical accuracy/Turnaround time) × (Utility/Costs). Recently, some researches used multicriteria decision analysis which allows comparison of diagnostic strategies in terms of benefits, opportunities, costs and risks. All analyses are constructed to identify laboratory test that produce the greatest healthcare benefit with the resources available. Without solid evidence that certain laboratory tests are cost-effective, laboratory services cannot be improved. Consequently, simple policy measures such as cost cutting may be imposed upon many laboratories while patients will have limited access to laboratory service.
Darko D. Dželajlija, Slavica S. Spasić, Jelena M. Kotur-Stevuljevic and Nataša B. Bogavac-Stanojevic
Background: Atherosclerosis is a chronic inflammatory disease which starts early in life and depends on many factors, an important one being dyslipoproteinemia. According to several studies, atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, interaction with a sedentary way of life, as well as unhealthy nutrition, smoking, alcohol consumption, obesity and family history of cardiovascular disease cause the burden of atherosclerotic disease.
Methods: Study included 624 children (316 boys, 308 girls), aged from 7-13 years. We analysed socio-demographic data (BMI, blood pressure, cardiovascular family history, smoking status), as well as lipid status with lipoprotein little a-Lp(a), and apolipoproteins: Apo AI, Apo B-100 for all children. This enabled us to calculate new atherogenic indices Tg/HDL-c, lipid tetrad index (LTI) and lipid pentad index (LPI). Cardiovascular risk for later life was estimated by using modified Risk Score for Young Individuals (RS), which divided the subjects according to the score level: low, medium and higher risk.
Results: The older children (13 y) had better lipid status than the younger children, i.e. significantly lower total cholesterol, LDL-C, triglycerides and non-HDL-C concentration and significantly higher HDL-C concentration than the younger children and this was in accordance with the RS level. Children with a positive family history of CV disease had significantly higher Lp(a) concentration and blood pressure. LPI was significantly higher in children with a higher RS.
Conclusions: The results of our work could be used for cardiovascular risk assessment in apparently healthy children to provide preventive measures which could control the change able risk factors.
Miron Sopić, Jelena Joksić, Vesna Spasojević-Kalimanovska, Nataša Bogavac-Stanojević, Sanja Simić-Ogrizović, Milica Kravljača and Zorana Jelić Ivanović
Background: Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects.
Methods: This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR.
Results: Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=−0.472, P=0.006; HD: r=−0.375, P=0.038), triglycerides (CG: r=−0.490, P=0.004; HD: r=−0.488, P=0.005), insulin (CG: r=−0.386, P=0.038; HD: r=−0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=−0.672, P<0.001; HD: r=−0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups.
Conclusions: Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of »adiponectin resistance«.
Background: We compared factors of inflammation – high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity.
Methods: The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1–3), representing significant stenosis in one, two or three vessels.
Results: We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1–3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1–3) patients (AUC=0.770, p<0.001).
Conclusion: PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application.
Ana Ninić, Nataša Bogavac-Stanojević, Miron Sopić, Jelena Munjas, Jelena Kotur-Stevuljević, Milica Miljković, Tamara Gojković, Dimitra Kalimanovska-Oštrić and Vesna Spasojević-Kalimanovska
Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients.
This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction.
Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034).
Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood.
Bosa Mirjanic-Azaric, Sanja Avram, Tanja Stojakovic-Jelisavac, Darja Stojanovic, Mira Petkovic, Natasa Bogavac-Stanojevic, Svetlana Ignjatovic and Marina Stojanov
Background: The aim of this study was to determine the reference values for thyrotropin (TSH), thyroid hormones (total and free thyroxine, T4 and fT4; total and free triiodothyronine, T3 and fT3), thyroglobulin (Tg) and thyroid antibodies (thyroid peroxidase, TPOAb and thyroglobulin antibody, TgAb) in the population of the Republic of Srpska.
Methods: A total of 250 euthyroid subjects were enrolled in this study. A direct method for choosing reference subjects was used to establish reference intervals. The hormones and thyroid antibodies were measured by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics, Mannheim, Germany). We calculated the reference intervals by MedCalc, version 220.127.116.11 (MedCalc software, Belgium) as recommended by the IFCC (CLSI C28-A3).
Results: Using guidelines recommended by the National Academy of Clinical Biochemistry (NACB) and based on standard statistical approaches, the reference intervals derived for TSH, fT4, T4, fT3, T3 were 0.75-5.32 mlU/L, 12.29-20.03 pmol/L, 73.49-126,30 nmol/L, 4.11-6.32 pmol/L, 1.15-2.32 nmol/L and for Tg, TPOAb, TgAb were 3.63-26.00 mg/L, <18.02 mlU/L, < 98.00 mlU/L, respectively. We found a significant difference (p<0.05) in TSH and fT3 values between different age groups as well as in T4, fT4 and fT3 values between gender groups.
Conclusions: The established reference values for the population of the Republic of Srpska were significantly different from the values recommended by the manufacturer of reagents (Roche Diagnostics). Our results showed that a laboratory needs to establish its own reference values in order to set up a proper diagnosis, as well as to treat patients successfully.