<p>UVOD: Ateroskleroza je najče&scaron;ća bolest karotidnih arterija i uzrok je oko 20% svih ishemijskih moždanih udara (IMU). Osim stepena stenoze i određene karakteristike karotidnog plaka označavaju povi&scaron;en rizik za IMU. Ultrazvukom je moguće pouzdano evaluirati aterosklerotske promene na karotidnim arterijama. Iako su faktori rizika (FR) za aterosklerozu istovremeno i FR za IMU, prisustvo identičnih FR kod pacijenata sa IMU, ne znači i prisustvo istog stepena ateroskleroze na karotidnim arterijama. CILJ: Utvrđivanje povezanosti pojedinih ultrazvučnih karakteristika karotidne ateroskleroze, sa prisustvom različitih kardiometaboličkih FR i njihovih biomarkera, kod pacijenata sa IMU. MATERIJAL I METODE: U istraživanje je uključeno 120 pacijenata sa nekardioembolijskim IMU u karotidnom slivu koji su podeljeni u dve grupe; 60 sa lakunarnim i 60 sa nelakunarnim infarktom mozga. Svim pacijentima je određivano prisustvo FR, kao &scaron;to su hipertenzija, dijabetes, hiperlipoproteinemija, pu&scaron;enje, gojaznost, metabolički sindrom, hiperhomocisteinemija i inflamacija. Beležene su vrednosti krvnog pritiska, glikemije, glikoliziranog hemoglobina, parametara lipidskog statusa, apolipoproteina (Apo) A-I i B, lipoproteina a, indeksa telesne mase (BMI), homocisteina, C reaktivnog proteina (CRP). Pomoću karotidnog dupleks ultrazvuka određivane su vrednosti intima-medijalnog zadebljanja (IMT), morfologija plaka, povr&scaron;ina plaka, stepen stenoze. Demografske karakteristike, FR i njihovi biomarkeri, te ultrazvučne karakteristike karotidne ateroskleroze, poređene su između dve grupe pacijenata. Kori&scaron;ćeni su hi-kvadrat test i t-test. Korelacije FR i vrednosti njihovih biomarkera sa različitim karakteristikama karotidnog plaka, određivane su upotrebom Pearsonovog koeficijenta korelacije r i Kramerovog V. Upotrebom regresionih analiza ispitivan je prediktivni značaj određenih FR i njihovih biomarkera u pojavi pojedinih karakteristika karotidnog plaka. REZULTATI: Vi&scaron;e pacijenata sa lakunarnim infarktom je imalo hipertenziju (98.3% naspram 85%; p=0.021). Pacijenti sa lakunarnim infarktom imali su veće vrednosti BMI (27.6 kg/m2 naspram 25.9 kg/m2; p=0.029), dok su pacijenti sa nelakunarnim infarktom imali veće vrednosti CRP (16.4 mg/l naspram 6.8 mg/l; p=0.001). Demografske karakteristike, ostali FR i njihovi biomarkeri, kao i vrednosti karotidnog IMT se nisu značajno razlikovali između dve grupe pacijenata. Pacijenti sa nelakunarnim infarktom su imali veći stepen karotidne stenoze (79.7% naspram 33.2%; p=0,0001), kao i če&scaron;će prisustvo heterogenog plaka (73.3% naspram 35%; p&lt;0,001), hipoehogenog plaka (51.7% naspram 16.7%; p&lt;0.001) i neravnog plaka (81.7% naspram 21.7%; p&lt;0,001). Sa vrednostima IMT značajno (p&lt;0.05) su korelirali životna dob pacijenata (r=0.276), dijabetes (Cramerovo V=0.236), metabolički sindrom (Cramerovo V=0.247), HDL holesterol (r=-0.254), LDL/HDL (r=0.306), ApoA-I (r=-0.386) i ApoB/ApoA-I (r=0.359). Sa prisustvom heterogenog plaka su korelirali metabolički sindrom (Cramerovo V=0.246), ApoB (r=0.213), ApoB/ApoA-I (r=0.207) i povi&scaron;en CRP (Cramerovo V=0.266). Sa neravnom povr&scaron;inom plaka značajno je korelirao povi&scaron;en CRP (Cramerovo V=0.283). Sa stepenom stenoze značajno su korelirali BMI (r=-0.180) i povi&scaron;en CRP (Cramerovo V=0.301). Nezavisni prediktori povi&scaron;enih vrednosti IMT bili su starija životna dob pacijenata (&beta;=0.230; p=0.006), ApoA-I (&beta;=-0.244; p=0.008) i ApoB/ApoA-I (&beta;=0.247; p=0.007). Prediktori prisustva heterogenog plaka bili su mu&scaron;ki pol (p=0.011; OR=3.425), ApoB (p=0.007; OR=8.972), BMI (p=0.0001; OR=0.380), metabolički sindrom (p=0.003; OR=4.555) i povi&scaron;en CRP (p=0.018; OR=2.800). Prediktori prisustva hipoehogenog plaka bili su ApoB (p&lt;0.001; OR=29.2), BMI (p=0.02; OR=0.514), metabolički sindrom (p&lt;0.001; OR=9.224) i povi&scaron;en CRP (p=0.046; OR=2.659). Povi&scaron;en CRP bio je jedini prediktor prisustva neravnog plaka (p=0.002; OR=3.203), kao i prisustva većeg stepene karotidne stenoze (&beta;=0.270; p=0.002). ZAKLJUČAK: Iako je karotidna stenoza znatno zastupljenija među pacijenatima sa nelakunarnim nego lakunarnim nekardioembolijskim IMU, prisustvo kardiometaboličkih FR, njihovih biomarkera i vrednosti IMT se bitno ne razlikuje između ove dve grupe pacijenata. Osim stenoze i prisustvo heterogenog, hipoehogenog i neravnog karotidnog plaka nosi povi&scaron;en rizik za IMU. Među FR i njihovim biomarkerima ApoA-I i ApoB su najbolji prediktori karotidne ateroskleroze. Apolipoprotein B i metabolički sindrom su najjače povezani sa prisustvom heterogenog i hipoehogenog plaka. Povi&scaron;en CRP kod pacijenata sa akutnim IMU može biti znak destabilizacije plaka i ukazivati na prisustvo signifikantne karotidne stenoze.</p> / <p>INTRODUCTION: Atherosclerosis is the most common disease of carotid arteries, causing 20% of all ischemic strokes. Besides the degree of stenosis, certain characteristics of carotid plaques indicate an increased risk for stroke. Carotid ultrasound can reliably evaluate atherosclerotic changes in carotid arteries. Although the risk factors for atherosclerosis are the same as the risk factors for stroke, the presence of identical risk factors in patients with stroke does not necessarily mean the presence of the same degree of carotid atherosclerosis. AIM: To determine correlation of certain characteristics of carotid atherosclerosis detected by ultrasound with the presence of various cardiometabolic risk factors in patients with ischemic stroke. METHODS: The study included 120 patients with noncardioembolic ischemic stroke in the anterior circulation, who were divided into two groups; 60 with lacunar and 60 with nonlacunar brain infarction. The presence of cardiometabolic risk factors, such as hypertension, diabetes, hyperlipoproteinemia, smoking, obesity, metabolic syndrome, hyperhomocysteinemia, and inflammation, was evaluated in all patients. Data regarding blood pressure, glycemia, glycated hemoglobin, lipid status parameters, apolipoprotein (ApoAI and ApoB), lipoprotein a, body mass index (BMI), homocysteine, and C-reactive protein (CRP) were collected. Intima-media thickness (IMT), carotid plaque characteristics (morphology, surface) and the degree of stenosis were determined by carotid duplex ultrasound. Demographic characteristics, risk factors, biomarkers, as well as ultrasound characteristics of carotid atherosclerosis, were compared between patients with lacunar and nonlacunar stroke. Two-sample student t-test and &chi;2 test were used for comparisons. In order to assess the correlation of various risk factors and their biomarkers with different characteristics of carotid plaques, we used the Pearson correlation coefficient r and Cramer&#39;s V. Regression analysis was used to evaluate the association of risk factors and their biomarkers with various carotid atherosclerosis characteristics. RESULTS: More patients with lacunar stroke had hypertension (98.3% vs. 85%; p=0.021). Patients with lacunar stroke had higher BMI values (27.6 kg/m2 vs. 25.9 kg/m2; p=0.029), while patients with nonlacunar stroke had higher CRP values (16.4 mg/l vs. 6.8 mg/l; p=0.001). Demographic characteristics, other risk factors and their biomarkers, as well as carotid IMT were not significantly different between the two groups of patients. Patients with nonlacunar stroke had a higher degree of carotid stenosis (79.7% vs. 33.2%; p=0.0001) and a higher prevalence of heterogeneous plaques (73.3% vs. 35%; p&lt;0.001), hypoechogenic plaques (51.7% vs. 16.7%; p&lt;0.001), and plaques with irregular surface (81.7% vs. 21.7%; p&lt;0,001). IMT was significantly (p&lt;0.05) correlated with the age of patients (r=0.276), diabetes (Cramer&rsquo;s V=0.236), metabolic syndrome (Cramer&rsquo;s V=0.247), HDL cholesterol (r=-0.254), LDL/HDL (r=0.306), ApoA-I (r=-0.386) and ApoB/ApoA-I (r=0.359). The presence of a heterogeneous plaque was correlated with metabolic syndrome (Cramer&rsquo;s V=0.246) ApoB (r=0.213), ApoB/ApoA-I (r=0.207) and elevated CRP (Cramer&rsquo;s V=0.266). A plaque with irregular surface was correlated with elevated CRP (Cramer&rsquo;s V=0.283). The degree of carotid stenosis was correlated with BMI (r=-0.180) and elevated CRP (Cramer&rsquo;s V=0.301). The independent predictors of higher values of IMT were older age (&beta;=0.230; p=0.006), ApoA-I (&beta;=-0.244; p=0.008), and ApoB/ApoA-I (&beta;=0.247; p=0.007). The predictors of the presence of a heterogeneous plaque were male gender (p=0.011; OR=3.425), ApoB (p=0.007; OR=8.972), BMI (p=0.0001; OR=0.380), metabolic syndrome (p=0.003; OR=4.555) and elevated CRP (p=0.018; OR=2.800). The predictors of the presence of a hypoechogenic plaque were ApoB (p&lt;0.001; OR=29.2), BMI (p=0.02; OR=0.514), metabolic syndrome (p&lt;0.001; OR=9.224) and elevated CRP (p=0.046; OR=2.659). Elevated CRP was the only independent predictor of a plaque with irregular surface (p=0.002; OR=3.203) and of a higher degree of carotid stenosis (&beta;=0.270; p=0.002). CONCULSIONS: Although carotid stenosis is significantly more pronounced in patients with nonlacunar than those with lacunar noncardioembolic ischemic stroke, cardiometabolic risk factors, their biomarkers and carotid IMT do not differ significantly between the two groups of patients. In addition to stenosis, a presence of heterogeneous, hypoechogenic and irregular-surface carotid plaques indicates an increased risk for ischemic nonlacunar stroke. Among the cardiometabolic risk factors and their biomarkers, ApoAI and ApoB have the strongest association with carotid atherosclerosis. Apolipoprotein B and metabolic syndrome have the strongest association with a heterogeneous and hypoechogenic carotid plaque. Elevated CRP in patients with acute ischemic stroke may be a sign of carotid plaque destabilization and can indicate a significant carotid stenosis.</p>

<p>UVOD: Gojaznost je hronično, multifaktorijalno i kompleksno oboljenje povezano sa povećanim rizikom od aterosklerotskih kardiovaskularnih bolesti (KVB). Disfunkcija vaskularnog endotela predstavlja rani događaj u patofiziolo&scaron;kom kontinuumu aterosklerotskog procesa, a produženo izlaganje vaskularnog endotela faktorima rizika za aterosklerozu udruženim sa gojaznosti (insulinska rezistencija, dislipidemija, proinflamatorno/protrombozno stanje), može doprineti procesima aktivacije/disfunkcije endotela i progresiji ateroskleroze u supkliničku, odnosno kliničku formu bolesti. CILJ: Uporediti koncentracije solubilne forme adhezionih molekula &ndash; intracelularnog adhezivnog molekula &ndash;1 (sICAM&ndash;1) i E selektina (sE&ndash;selektin), između ispitanika sa hiperalimentacionim tipom gojaznosti i normalno uhranjenih zdravih ispitanika, kao i utvrditi eventualno postojanje razlika u koncentraciji sICAM&ndash;1 i sE&ndash;selektina između ispitanika kod kojih je merenjem debljine kompleksa intima medija karotidne arterije (IMK) uočen supklinički stadijum ateroskleroze i ispitanika koji imaju normalnu debljinu IMK. Ispitati povezanost parametara telesne kompozicije (ukupne masne mase tela i masne mase abdominalnih depoa), cirkuli&scaron;ućih koncentracija biomarkera disfunkcije vaskularnog endotela (sICAM&ndash;1 i sE&ndash;selektina) i IMK kod ispitanika sa hiperalimentacionim tipom gojaznosti. MATERIJAL I METODE: U istraživanje je uključeno 60 ispitanika sa hiperalimentacionim tipom gojaznosti bez pridruženih komorbiditeta i 30 zdravih normalno uhranjenih učesnika usklađenih sa ispitanicima po godinama života i polu koji su činili kontrolnu grupu. Svim ispitanicima su urađena antropometrijska merenja, analiza komponenata telesne kompozicije (bioelektrična impedansna analiza, Tanita Body Composition Analyzer BC &ndash; 418 MA III), laboratorijska analiza uzoraka krvi na automatizovanim analizatorskim sistemima sa određivanjem parametara metabolizma glukoze (bazalno i 2 h u toku oralnog glukoza tolerans testa), lipida i lipoproteina, inflamacije i homocisteina. Određivanje serumske koncentracije sICAM&ndash;1 i sE&ndash;selektina je vr&scaron;eno ELISA tehnikom (R&amp;D Systems, Inc. Minneapolis, USA). Vrednosti IMK&ndash;a su određivane pomoću karotidnog dupleks ultrazvuka (Aloka SSD&ndash;650 US system, Tokyo), a na osnovu izmerenih (IMK) i normalno očekivanih vrednosti IMK za svakog ispitanika je izračunavan IMK Z&ndash;skor. Supklinički stadijum ateroskleroze je definisan kao vrednost IMK Z&ndash;skora veća od 1 (&scaron;to odgovara vrednosti IMK većoj od 95 percentila normalno očekivane vrednosti u odnosu na pol i godine života ispitanika). REZULTATI: Ispitanici sa hiperalimentacionim tipom gojaznosti su imali statistički značajno vi&scaron;e vrednosti medijane serumske koncentracije sE&ndash;selektina u poređenju sa medijanom serumske koncetracije sE&ndash;selektina učesnika u kontrolnoj grupi (36,2 (33,21&ndash;43.7) vs. 25,14 (23,1&ndash;29,48) ng/mL, P=0,00). Gojazni ispitanici III stepena gojaznosti su imali statistički značajno vi&scaron;u medijanu serumske koncenracije sE&ndash;selektina u odnosu na medijanu sE&ndash;selektina u ispitanika I stepena gojaznosti (41,5 (36,58&ndash;49,48) vs. 34,34 (22,49&ndash;36,62) ng/mL, P=0,00), odnosno medijanu sE&ndash;selektina u ispitanika II stepena gojaznosti (41,5 (36,58&ndash;49,48) vs. 32,1 (26,1&ndash;43,64) ng/mL, P=0,00). Nije uočena statistički značajna razlika u medijani serumske koncentracije sE&ndash;selektina između ispitanika I i II stepena gojaznosti (34,34 (22,49&ndash;36,62) vs. 32,1 (26,1&ndash;43,64) ng/mL, P=0,12). Gojazni ispitanici su imali statistički značajno vi&scaron;e vrednosti medijane serumske koncentracije sICAM&ndash;1 u poređenju sa medijanom serumske koncetracije sICAM&ndash;1 učesnika u kontrolnoj grupi (266,8 (245,8&ndash;326,73) vs.183,32 (167,9&ndash;208,57), P=0,00). U ispitivanoj grupi gojaznih uočena je statistički značajna razlika u medijani koncentracije sICAM&ndash;1 između ispitanika u I, II i III stepena gojaznosti (200,6 (190,26 - 264,4) vs. 278,5 (219,54 - 343,24) vs. 329,6 (259,2 - 350,34) ng/mL, P=0,00). Učestalost IMK Z&ndash;skor &gt; 1 je bila statistički značajno eća u gojaznih ispitanika u odnosu na kontrolnu grupu (36/60 vs. 7/30, P=0,00). Ispitanici sa IMK Z&ndash;skor &gt; 1 su imali statistički značajno vi&scaron;u medijanu koncentracije sICAM&ndash;1 u odnosu na ispitanike kod kojih je IMK Z&ndash;skor &le; 1 (295,4 (238,46&ndash;340,38) vs. 244,2 (227,35&ndash;260,38), P=0.00). Regresionom analizom (R2=0,71, korigovani R2=0,59) je utvrđeno da su parametri hsCRP (&beta;=0,45, P=0,00), HOMA&ndash;IR (&beta;=0,44, P=0,035) i ISI (&beta;=&ndash;0,36, P=0,028) nezavisno i statistički značajno povezani sa serumskom koncentracijom sE&ndash;selektina. Regresionom analizom (R2=0,65, korigovani R2=0,56) je utvrđeno da parametri ITM (&beta;=0,55, P=0,00), trigliceridi (&beta;=0,30, P=0,00), HDL holesterol (&beta;=&ndash;0,31, P=0,00), odnos TG/HDL&ndash;holesterol (&beta;=0,33, P=0,01), hsCRP (&beta;=0,31, P=0,00) i fibrinogen (&beta;=0,34, P=0,00) su nezavisno i statistički značajno povezani sa serumskom koncentracijom sICAM&ndash;1. U faktorskoj analizi je izdvojeno pet faktora &ldquo;gojaznost&rdquo;, &ldquo;insulinska rezistencija&rdquo;, &ldquo;aterogeni faktor&rdquo;, &ldquo;endotelna disfunkcija i vaskularna inflamacija&rdquo; i &ldquo;metabolički faktor&rdquo; koji obja&scaron;njavaju 69.72% ukupne varijanse ispitivanog uzorka. U multivarijabilnom modelu sa svim faktorima zajedno kojim je obja&scaron;njeno ukupno 75% varijanse, jedino je faktor gojaznost imao statički značajan i nezavistan uticaj na vrednost IMK Z&ndash;skor &gt; 1 (OR=2,74 (CI 1,18&ndash;6,33), P=0,019). U faktoru gojaznost su se izdvojili parametri: FAT trunk (%), FAT (%), OS (cm), ITM (kg/m2), LDL &ndash; holesterol (mmol/L), SP (mmHg), HOMA1&ndash;%B, fibrinogen (g/L), ApoB/apoA-I i hsCRP (mg/L). Univarijantom logističkom regresijom je uočeno da porast u koncentraciji LDL&ndash;H (OR=5,33 (CI 1,9&ndash;14,2), P=0,02) i koncentraciji hsCRP&ndash;a (OR=2,53 (CI 1,3&ndash;3,98),P=0,017) povećava rizik za postojanje vrednosti IMK Z&ndash;skor &gt; 1. ZAKLJUČAK: Cirkuli&scaron;uće serumske koncentracije biomarkera disfunkcije vaskularnog endotela, sE&ndash;selektina i sICAM&ndash;1, su značajno vi&scaron;e kod ispitanika sa hiperalimentacionim tipom gojaznosti u odnosu na njihove koncentracije u normalno uhranjenih ispitanika. U gojaznih ispitanika, koncentracija sE&ndash;selektina je povezana sa vrednostima indeksa insulinske rezistencije i biomarkera inflamacije, dok je koncentracija sICAM&ndash;1 značajno povezana sa udelom masne mase u ukupnoj telesnoj masi, vrednostima biomarkera inflamacije i proaterogenih lipidskih parametara. Ispitanici kod kojih postoji uvećanje abdominalnih masnih depoa i ukupnog udela masnog tkiva u telesnoj masi, vrednosti SKP, koncentracije LDL &ndash; holesterola, vrednosti lipoproteinskog indeksa ApoAI/apoB, bazalne insulinemije i biomarkera inflamacije, imaju trostruko povećan rizik od supkliničkog stadijuma ateroskleroze. U gojaznih osoba prilikom procene rizika od aterosklerotskih KVB, potrebno je utvrditi fenotipske osobine vaskularnog endotela i eventualno postojanje supkliničkog stadijuma ateroskleroze, da bi se definisale adekvatne preventivne mere i sagledale potencijalne terapijske mogućnosti.</p> / <p>INTRODUCTION: Obesity is a chronic, multifactorial and complex disease associated with an increased risk of atherosclerotic cardiovascular diseases (CVD). Vascular endothelial dysfunction is an early event in the pathophysiological continuum of atherosclerotic process. The prolonged exposure of vascular endothelium to classical and obesity associated risk factors (insulin resistance, dyslipidemia, proinflammatory state) could further promote deterioration of endothelial function and progression of atherosclerosis to subclinical or clinical form of disease. OBJECTIVE: The aim of the study was to compare the concentration of soluble forms of adhesion molecules, intracellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin), between obese subjects and normal weight healthy subjects, as well as to determine the possible existence of differences in concentration of sICAM-1 and sE-selectin among subjects with subclinical stage of atherosclerosis (assessed by measuring the thickness of the intima media complex of the carotid artery (IMT)), and subjects who have a normal value of IMT. Also, the aim was to determine the association between the parameters of body composition (total body fat mass and fat mass intra-abdominal depots), circulating concentrations of sICAM-1 and sE-selectin, and value of IMT in obese subjects. MATERIALS AND METHODS: The study included 60 obese nondiabetic subjects, without preexisting CVD and other associated comorbidity, and 30 healthy normal weight age and sex matched participants. All subjects underwent anthropometric measurements, analysis of the components of body composition (bioelectrical impedance analysis, Tanita Body Composition Analyzer BC - 418 MA III), laboratory analysis of blood samples (automated analyzer systems) with determining the parameters of glucose metabolism (basal and 2 h during the oral glucose tolerance test), lipids and lipoproteins, inflammation and homocysteine. Serum concentrations of sICAM-1 and sE-selectin were determined by ELISA (R &amp; D Systems, Inc., Minneapolis, USA). The values of IMK were determined by carotid duplex ultrasound (Aloka &ndash; ProSound ALPHA 10). IMK Z-score was calculated using the measured and the normal expected values of IMT for each patient. Subclinical stage of atherosclerosis was defined as the value of IMT Z-score greater than 1 (corresponding to the 95th sex-age-specific percentile of IMT measurements). RESULTS: Obese subjects had significantly higher median sE-selectin serum concentrations compared to median serum concentrations of sE-selectin in the normal weight subjects (36.2 (33.21-43.7) vs 25.14 (23.1-29.48) ng/mL, P=0.00). Morbid obesity subjects had significantly higher sE-selectin median serum concentration compared to the median sE-selectin concentration in moderate obese subjects (41.5 (36.58-49.48) vs 34.34 (22.49-36.62) ng/mL, P=0.00), and compared to the median sE-selectin concentration in severely obese subjects (41.5 (36.58-49.48) vs. 32.1 (26.1-4364) ng / mL, P=0.00). Obese subjects had significantly higher median sICAM-1 serum concentration compared to median sICAM-1 serum concentration in the control group (266.8 (245.8-326.73) vs. 183.32 (167.9-208.57), P=0.00). In the obese group, we observed a statistically significant difference in median sICAM-1 serum concentrations between moderate, severely and morbid obese subjects (200.6 (190.26-264.4) vs. 278.5 (219.54-343.24) vs. 329.6 (259.2-350.34) ng/mL, P=0.00). The frequency of IMT Z-score&gt; 1 was significantly higher in the obese group compared to control group (36/60 vs. 7/30, P=0.00). Subjects with IMT Z-score&gt; 1 had significantly higher median concentrations of sICAM-1 compared to those in which the IMK Z-score &le; 1 (295.4 (238.46-340.38) vs. 244.2 ( 227.35-260.38), P=0.00). In regression analysis (R2=0.71, adjusted R2=0.59), hsCRP (&beta;=0.45, P=0.00), HOMA-IR (&beta;=0.44, P=0.035) and ISI (&beta;=-0.36, P=0.028) were independently and significantly associated with serum sE-selectin concentration. In regression analysis (R2=0.65, adjusted R2=0.56), BMI (&beta;=0.55, P=0.00), triglycerides (&beta;=0.30, P=0.00), HDL cholesterol (&beta;=-0.31, P=0.00), the ratio of TG/HDL-cholesterol ratio (&beta;=0.33, P=0.01), hsCRP (&beta;=0.31, P=0.00 ) and fibrinogen (&beta;=0.34, P=0.00) were independently and significantly associated with serum sICAM-1 concentration. In the Factor analysis, five factors &quot;obesity&quot;, &quot;insulin resistance&quot;, &quot;atherogenic factor,&quot; &quot;endothelial dysfunction and vascular inflammation&quot; and &quot;metabolic factor&quot; explained 69.72% of the total variance of the test sample. In a multivariate model with all the factors together (75% of the total variance), &quot;obesity&quot; factor was significantly and independently associated with IMT Z-score&gt; 1 (OR=2.74 (CI 1.18-6.33), P=0.019). The &quot;obesity&quot; factor consisted of parameters: trunk fat (%), fat (%), waist (cm), BMI (kg/m2), LDL &ndash; cholesterol (mmol/L), systolic blood presure (mmHg), HOMA1-% B, fibrinogen (g/L), Apo B/apoA-I and hsCRP (mg/L). Logistic regression analysis showed that independent predictors of IMT Z-score&gt; 1 were LDL-cholesterol (OR=5.33(CI 1.9-14.2), P=0.02) and hsCRP (OR=2.53 (CI 1.3-3.98), P=0.017). CONCLUSION: Circulating serum concentrations of endothelial dysfunction biomarkers, sE-selectin and sICAM-1, were significantly higher in obese subjects compared to concentration in the normal weight subjects. In obese subjects, the concentration of sE-selectin was associated with insulin resistance and biomarkers of inflammation, whereas sICAM-1 concentration was associated with fat mass, inflammation biomarkers and the proatherogenic lipid parametars. In individuals with increased abdominal fat depots and total proportion of fat mass in the body weight, values of SBP, LDL-C, ApoB/apoA-I, basal insulin levels and biomarkers of inflammation, there is threefold increased risk of subclinical stages of atherosclerosis. In order to define an adequate preventive measures and possible therapeutic options for atherosclerotic CVD in obese subjects, it is necessary to assess the phenotypic characteristics of vascular endothelium and possible presence of subclinical stage of atherosclerosis.</p>

<p>Gojaznost se najče&scaron;će defini&scaron;e kao uvećanje udela masne mase u ukupnoj telesnoj masi. Danas gojaznost poprima pandemijske razmere i karakter globalnog zdravstveno-socijalnog problema jer predstavlja faktor rizika za razvoj masovnih nezaraznih bolesti, pre svega tipa 2 &scaron;ećerne bolesti (T2DM) i kardiovaskularnih bolesti. Adipokini su molekule koje luči masno tkivo i koji imaju značajnu ulogu u regulaciji mnogobrojnih procesa u ljudskom organizmu. Adiponektin (ADN) je adipokin sa antidijabetogenim, antiinflamatornim i antiaterogenim dejstvom. Tokom razvoja, pre svega, centralnog tipa gojaznosti dolazi do poremećaja u sekretornom profilu masnog tkiva, nastaje pad serumske koncentracije ADN i dolazi do razvoja mnogobrojnih kardiometaboličkih poremećaja. Cilj rada je ispitivanje značaja određivanja serumskog ADN u proceni kardiometaboličkog profila i utvrđivanje povezanosti njegovog nivoa sa procenjenim desetogodi&scaron;njim rizikom za razvoj T2DM kod gojaznih osoba. Studija preseka sprovedena na Klinici za endokrinologiju, dijabetes i bolesti metabolizma, Kliničkog centra Vojvodine je obuhvatila 65 ispitanika sa hiperalimentacionim tipom gojaznosti. Kod ispitanika je procenjen desetogodi&scaron;nji rizik za razvoj T2DM i sprovedena su odgovarajuća antropometrijska, laboratorijska i morfolo&scaron;ka ispitivanja. Ispitanici sa sniženim serumskim ADN su imali nepovoljniji kardiometabolički profil u odnosu na ispitanike sa normalnom vredno&scaron;ću serumskog ADN dok nije bilo razlike u nivou desetogodi&scaron;njeg rizika za razvoj T2DM između navedenih grupa. Takođe, ispitanici sa metaboličkim sindromom (MS) i ispitanici sa nealkoholnom masnom bole&scaron;ću jetre (NAFLD) su imali niži serumski ADN u odnosu na osobe bez MS i osobe bez NAFLD. Kod gojaznih osoba postoji značajna povezanost serumskog ADN sa većim brojem pokazatelja kardometaboličkog profila ali ne i sa procenjenim desetogodi&scaron;njim rizikom za razvoj T2DM.</p> / <p>Obesity is often defined as the significant increase in proportion of fat mass in total body mass. Nowadays, obesity exhibits pandemic proportions and acquires character of the global health and social problem, as it represents the risk factor for the development of non-communicable diseases, especially type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Adipokines are molecules secreted by adipose tissue which play an important role in the regulation of various processes in the human organism. Adiponectin (ADN) is an adipokine with anti-diabetic, anti-inflammatory and anti-atherogenic effects. During development of, above all, central obesity, disorders in the secretory profile of adipose tissue are arising, decline in serum concentrations of ADN advents, which leads to occurrence of numerous cardiometabolic disorders. The aim of study is to examine the significance of determining serum ADN in assessing the cardiometabolic profile, and determining its association with the estimated ten-year risk of developing T2DM in obese persons. Cross-sectional study conducted at the Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, included 65 persons with hyperalimentation type of obesity. Ten-year risk of developing T2DM was assessed and appropriate anthropometric, laboratory and morphological evaluations were performed. Persons with lower serum ADN had worse cardiometabolic profile compared to those with normal serum ADN value, while there was no difference in the level of ten-year risk of developing T2DM between two groups. Also, subjects with metabolic syndrome (MS) and subjects with nonalcoholic fatty liver disease (NAFLD) had lower serum ADN compared to persons without MS and to those without NAFLD. There is a significant association of serum ADN with a larger number of cardiometabolic profile indicators but not with the estimated ten-year risk of developing T2DM.</p>

<p>S obzirom na visoku prevalencu metaboličkog sindroma (10-40% u svetskoj populaciji) i na činjenicu da prisustvo metaboličkog sindroma duplira rizik od nastanka aterosklerotske bolesti kardiovaskularnog sistema jasna je potreba za identifikacijom indivudualnih parametara koji doprinose njenom razvoju. Metabolički sindrom je klaster faktora rizika metaboličkog porekla koji je udružen sa povećanim rizikom za nastanak aterosklerotske bolesti kardiovaskularnog sistema i dijabetes melitusa tipa 2. Insulinska rezistencija, abdominalna gojaznost, aterogena dislipidemija, hipertenzija, proinflamatorno i protrombotično stanje su faktori koji su u osnovi metaboličkog sindroma a često su i praćeni nagomilavanjem masti u jetri. Cilj rada je bio da se utvrdi odnos između markera disfunkcije hepatocita (AST, ALT, GGT), serumskog nivoa inflamatornih biomarkera (broj leukocita, elektroforeza serumskih proteina, CRP, fibrinogen, TNF-&alpha;), biomarkera endotelne disfunkcije (ADMA i homocistein), kao i nivoa serumskih adipokina (leptin i adiponektin) i debljine intima-medija kompleksa (IMT) karotidne arterije kao pokazatelja prisustva aterosklerotskog procesa. Ispitivanje je dizajnirano kao studija preseka. U ispitivanje je uključeno 58 ispitanika oba pola sa karakteristikama metaboličkom sindroma (NCEP:ATP III kriterijumi). Odabir ispitanika je vr&scaron;en u Odeljenju za pravilnu ishranu i zdravstvenu bezbednost hrane, Instituta za javno zdravlje Vojvodine. Kontrolnu grupu su sačinjavale 30 klinički i biohemijski zdravih ispitanika nepu&scaron;ača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Iz ispitivanja su isključene osobe koje konzumiraju vi&scaron;e od 20g/dan alkohola, pu&scaron;ači, koji imaju dijagnostikovan virusni hepatitis B ili C ili pozitivan Hbs antigen, anti-Hbs antitela i anti-HCV antitela, osobe koje imaju verifikovana oboljenja kardiovaskularnog sistema, bubrega, CNS-a, infektivna, maligna i autoimuna oboljenja kao i druga oboljenja jetre i žučnih puteva, osobe koje su pod medikamentoznom terapijom koja može uticati na nivo serumskih biomarkera endotelne disfunckije, lipidni i lipoproteinski status, glikoregulaciju kao i menstruacioni ciklus. Sve laboratorijske analize su urađene u Centru za laboratorijsku medicinu, Kliničkog centra Vojvodine. Doppler ultrasonografski pregled karotidnih arterija i ultrazvuk abdomena i jetre je urađen u Centru za radiologiju Kliničkog centra Vojvodine. Signifikantna pozitivna korelacija niskog stepena je utvrđena između IMT zajedničke karotidne arterije i serumskih koncentracija GGT, hsCRP i leptina kao i odnosa neutrofili/limfociti. Prema prvom konstruisanom regresionom modelu u kojem je zavisna varijabla bila IMT preko 0,09 cm statistički značajan uticaj na predviđanje debljine IMT zajedničke karotidne arterije imaju hsCRP (Exp (B) 1,112 i glikemija (Exp (B) 1,973). Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju glikemija, AST i fibrinogen. Prema drugom konstruisanom regresionom modelu gde su zavisne varijable bile IMT zajedničke karotidne arterije preko 0,09 cm i prisutnost hepatične steatoze najveću mogućnost predviđanja imaju leptin Exp (B) 1,1022 i ALT Exp (B) 1,053. Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju ALT, ADMA i leptin.</p> / <p>Given the high prevalence of metabolic syndrome (10-40% in the world population) and the fact that the presence of metabolic syndrome doubles the risk of atherosclerotic disease of the cardiovascular system, there is a clear need to identify individual parameters that contribute to its development. Metabolic syndrome is a cluster of the risk factors of metabolic origin that is associated with an increased risk for the onset of atherosclerotic disease of the cardiovascular system and type 2 diabetes mellitus. Insulin resistance, abdominal obesity, atherogenic dyslipidemia, hypertension, proinflammatory and prothrombotic conditions are the factors at the base of the metabolic syndrome and are often accompanied by fat accumulation in the liver. The aim of this work was to determine the relation between markers of hepatic dysfunction (AST, ALT and GGT), serum levels of inflammatory biomarkers (white blood cell count, electrophoresis of serum proteins, CRP, fibrinogen, TNF-&alpha;), biomarkers of endothelial dysfunction (ADMA and homocysteine) as well as levels of serum adipokines (leptin and adiponectin) and intima-media thickness of carotid artery as indicators of atherosclerotic process in the patients with metabolic syndrome. Study was cross-sectional. It included 58 participants with metabolic syndrome (NCEP:ATP III criteria) as well as 30 clinically and biochemically healthy nonsmokers, age and gender matched controls. Participants were selected in the Department for Nutrition and Food Safety, Center of Hygiene and Human Ecology Institute of Public Health of Vojvodina. Patients that consumed alcohol more than 20g/day were excluded. Participants with positive HBsAg, anti-HBs-antibodies or anti- HCV antibodies were excluded also. Smokers were also excluded. Patients with cardiovascular diseases, renal diseases, infective, hepatic, malignant and autoimmune diseases were excluded from this study. Subjects which used drugs that could affect biomarker levels of endothelial dysfunction, lipid metabolism, glucose metabolism and menstrual cycle were also excluded. All laboratory analyzes were done in Centre for Laboratory Medicine, Clinical Centre of Vojvodina. Doppler ultrasonography of carotid arteries and ultrasound of abdomen and liver were done in Centre for Radiology, Clinical Centre of Vojvodina. Significant positive correlation of low degree was determined between IMT of common carotid artery and serum concentrations between GGT, hsCRP and leptin and relationship neutrophils/lymphocytes. According to the first constructed regression model where dependent variable was IMT of common carotid artery above 0.09 cm statistically significant influence on foreseeing IMT of common carotid artery have hsCRP (Exp (B) 1.112 and glycaemia (Exp (B) 1.973). According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have glycaemia, AST and fibrinogen. According to the second constructed regression model where dependent variable was IMT above 0.09 cm and present hepatic steatosis greatest probability for foreseeing IMT have leptin Exp (B) 1.1022 and ALT Exp (B) 1.053. According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have ALT, ADMA and leptin.</p>

<p>Izvod: UVOD: Metabolički zdrave gojazne osobe su okarakterisane odsustvom metaboličkog sindroma i/ili insulinske rezistencije i sistemske inflamacije. Mali je broj podataka o ulozi aktivnosti autonomnog nervnog sistema u razvoju kardiometaboličkih komplikacija kod gojaznih osoba, kao i o njegovoj vezi sa specifičnom distribucijom masnog tkiva. CILJ: Analiza varijabilnost srčane frekvencije (HRV) kod metabolički zdravih (MHO) i gojaznih osoba sa metaboličkim rizikom (MUO), analiza povezanosti HRV sa metaboličkim faktorima i distribucijom masnog tkiva, kao i analiza uzrasne dinamike HRV kod gojaznih osoba različitih kardiometaboličkih profila. MATERIJAL I METODE: Ukupno 125 gojaznih ispitanika oba pola podvrgnuto je antropometrijskim merenjima u cilju procene mase i distribucije masnog tkiva, izvr&scaron;ena je analiza telesne kompozicije, uzeti su uzorci krvi u cilju određivanja lipidskog i lipoproteinskog statusa, stanja glikoregulacije i nivoa inflamatornih markera, meren je krvni pritisak i procenjena je HRV tokom petominutne digitalne elektrokardiografije. Podaci su statistički obrađeni kori&scaron;ćenjem paketa SPSS 11.5. REZULTATI: HRV mere se nisu razlikovale statistički značajno među MHO i MUO mu&scaron;karcima. MHO žene su imale vi&scaron;e vrednosti RRNN, SDNN, RMSSD, pNN50, LF, HF i TP u odnosu na MUO žene, na čega metabolički profil utiče sa 6,6-11,2%(p˂0,01), predstavljeno kroz parcijalnu deljenu varijansu. Nakon antropometrijskih faktora uzetih u obzir, perzistirale su vi&scaron;e vrednosti HF kod MHO žena. Razlika u RRNN, pNN50 i TP između MHO i MUO premenopauzalnih žena (vi&scaron;e vrednosti za MHO, p˂0,05) se izgubila nakon kontrole za krvni pritisak. Insulinemija je uticala na pojave razlika u RRNN između MHO i MUO premenopauzalnih žena, parcijalna deljena varijansa 7,6%. SAD kod žena se negativno povezivao sa LF/HF i LFnorm, a pozitivno sa HFnorm, parcijalne deljene varijanse 8,4-11,9% (p˂0,05). Prednji nabor podlaktice kod žena se pozitivno povezivao sa LF i LF/HF, a negativno sa HFnorm (p˂0,01). Visceralna masna masa je predviđala značajno HRV mere mu&scaron;karaca, parcijalna deljena varijansa 13-34% (p˂0,01). U okviru gornjeg tercila HRV mera RMSSD, pNN50 i LF MUO osoba, HOMA indeks je statistički značajno niži (p˂0,05). Kod MUO osoba SDNN, RMSSD, lnpNN50, lnLF, lnHF i TP značajno su se smanjivali u uzrastu od 19-29 do 40-49 godina. Kod MHO osoba primetna je uzrasna promena HF mere u četvrtoj deceniji života. ZAKLJUČAK: MHO osobe ženskog pola imaju značajno vi&scaron;e vrednosti markera varijabilnosti srčane frekvencije u odnosu na MUO. Razlike u HRV merama su uslovljene kriterijumima metaboličke podele, predominantno insulinemijom, vrednostima krvnog pritiska i centralnom masnom masom. Kod žena centralna distribucija masnog tkiva korelira sa smanjenom srčanom simpatičkom aktivno&scaron;ću dok se periferna distribucija masnog tkiva povezuje obrnuto sa komponentama aktivnosti autonomnog nervnog sistema. Kod mu&scaron;karaca centralna masna masa, ali ne i periferna, je značajno povezana sa HRV. MUO osobe sa nižom HRV imaju veći stepen insulinske rezistencije, dok HRV ne utiče na insulinsku senzitivnost MHO osoba. Značajniji uzrasno zavisni pad HRV mera primetan je kod MUO osoba, pogađajući obe komponente autonomnog nervnog sistema za razliku od MHO osoba.</p> / <p>Abstract: INTRODUCTION: Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome and/or insulin resistance and inflammation. Little is known about the role of autonomic nervous system in development of cardiometabolic complications in obese people and about its influence on the specific adipose tissue distribution. AIM: Analysis of the hearth rate variability (HRV) in metabolically healthy (MHO) and unhealthy (MUO) obese people, its connection with adipose tissue distribution, and age dependent dynamics of HRV. MATERIAL AND METHODS: A total of 125 obese patients of both sexes underwent anthropometric measurements in order to assess adipose tissue mass and distribution, body composition was assessed, blood samples were taken in order to analyze parameters of lipid and lipoprotein profile, condition of glycoregulation and inflammatory markers, blood pressure was measured and short term HRV was conducted. Data were statisticaly analyzed using SPSS 11.5. RESULTS: HRV measures did not differ significantly between MHO and MUO men. MHO women had higher values of RRNN, SDNN, RMSSD, pNN50, LF, HF and TP compared to the MUO women, influence of metabolic profile was 6,6-11,2% (p˂0,01), presented through partial shared variance. After controlling for anthropometric factors higher HF persisted in MHO women. Differences in RRNN, pNN50 and TP between MHO and MUO premenopausal women (higher values of MHO, p˂0,05) were lost after controlling for blood pressure. Insulinemia influenced the difference in RRNN between MHO and MUO premenopausal women, partial shared variance 7,6%. SAD in women was connected negatively with the LF/HF and LFnorm, and positively with HFnorm, partial shared variance 8,4-11,9% (p˂0,05). Anterior forearm skinfold in women correlated positively with LF and LF/HF, and negatively with HFnorm (p˂0,01). Visceral fat mass predicted significantly HRV in men, partial shared variance 13-34% (p˂0,01). Within the upper tertile of HRV measures RMSSD, pNN50 and LF in MUO people, HOMA was significantly lower (p˂0,05). In MUO SDNN, RMSSD, lnpNN50, lnLF,lnHF and TP significantly decreased in the period from 19-29 to 40-49 years. In MHO people the change in HF was noticeable in the fourth decade of life. CONCLUSION: MHO women have significantly higher levels of HRV markers comparing to the MUO. The differences in HRV measures are influenced by metabolic criteria used, predominantly by insulinemia, blood pressure and central fat mass. In women, central distribution of adipose tissue correlates with reduced cardiac sympathetic activity, while the connection of peripheral fat mass distribution with components of autonomic nervuos system activity is reverse. In men, central fat mass, but not peripheral, is significantly associated with HRV. MUO people with lower HRV have a higher degree of insulin resistance, while the level of HRV measures does not affect insulin sensitivity in MHO individuals. Significant age-dependent decrease in both ANS representatives of HRV measures was noticed in MUO people, unlike MHO individuals.</p>