Association between left ventricular myocardial geomety and phenotypic characteristics of adipose tissue in obese individuals

Gojaznost je jedno od najznačajnjih oboljenja savremene medicine u grupi hroničnih nezaraznih bolesti. Posebno je važan uticaj uvećane masne mase tela u patogenezi kardiovaskularnih bolesti, sa mogućim posledicama za nastanak insuficijencije srca, koronarne insuficijencije, poremećaja ritma. Disproporcija u efektima agresivnih faktora, mehaničkih faktora zbog uvećanja telesne mase, i funkcionalnih zbog poremećaja adipokinske sekrecije i prisutnih faktora rizika, otežavaju prevenciju poremećaja na ciljnim organima. Sama činjenica da gojaznost kao hronična bolest dovodi do nastanka komorbiditeta na srcu, uz prisutne tradicionalne faktore rizika, stavlja u fokus interakciju proinflamatornih adipokina disfunkcionalnog masnog tkiva i poremećaj geometrije miokarada leve komore na prvo mesto. CILJ: Ispitati povezanost veličine subkutanih i visceralnih abdominalnih masnih depoa, cirkulišućih koncentracija hemerina i SFRP-5 i geometrije miokarda leve komore kod gojaznih bolesnika sa kardiometaboličkim sindromom, kao i utvrditi da li porast stepena kardiometaboličkog sindroma doprinosi većoj učestalosti poremećaja geometrije miokarda leve komore kod gojaznih ispitanika. MATERIJAL I METODE: Istraživanje je uključivalo gojazne ispitanike, bez pridruženih komorbiditeta, kao i zdrave normalno uhranjene ispitanike usklađene po godinama života i polu koji su činili kontrolnu grupu. Dodatno, ispitivana grupa je podeljena na tri podgrupe u odnosu na kriterijume za postojanje kardiometaboličkog sindroma. Svim ispitanicima su urađena antropometrijska merenja, analiza komponenata telesne kompozicije, laboratorijska analiza uzoraka krvi na automatizovanim analizatorskim sistemima, sa određivanjem parametara metabolizma glikoze (bazalno i 2 h u toku oralnog glukoza tolerans testa), lipida i lipoproteina i parametara inflamacije. Serumske koncentracije proinflamatornih adipokina, hemerina i rezistina, odnosno antiinflamatornog adipokina SFRP-5, su određivane ELISA tehnikom, Enzyme-linked immunosorbent Assay, proizvođača (R&D Systems, Inc., Minneapolis, USA). Ehokardiografski dvodimenzionalni transtorakalni pregledi srca (2D, pulsni, tkivni i kolor Doppler) izvođeni su, na ultrazvučnom aparatu Vivid 9, proizvođača “General Electrics Co”, korišćenjem sonde niske frekvencije od 2,5 MHz, dok je za ultrasonografsko merenje debljine visceralnog i subkutanog masnog tkiva korišćen aparat General Electric (GE) Logic 7. REZULTATI: Gojazni ispitanici imali su statistički značajno više vrednosti proinflamatornih adipokina hemerina i rezistina u poređenju sa normalno uhranjenim ispitanicima u kontrolnoj grupi (47,6 (41,4-54) vs 24,6 (16,8-32,4), P=0,00) i rezistina (4,73 (4,52-4,93) vs 3,75 (3,19-4,30), P=0,00), dok vrednosti antiinflamatornog SFRP-5 nemaju statistički značajnu razliku. Gojazni ispitanici imali su pozitivnu korelaciju serumske koncentracije proinflamatornog hemerina sa indeksom telesne mase (r=0,41, P=0,00), OS (r=0,46, P=0,00), OK (r=0,41, P=0,00), i FAT (kg) (r=0,36, P=0,00), sa obimom vrata (r=0,26, P=0,01) i sa procentom masnog tkiva FAT (kg) (r=0,28, P=0,01). Takođe, gojazni ispitanici su imali statistički pozitivnu korelaciju hemerina i parametara subkutanog masnog tkiva ((Max SFTa r=0,35, P=0,00), (Max SFTb r=0,45, P=0,00), (Max PFT r=0,34, P=0,00)) i intraabdominalnog masnog tkiva (r=0,37, P=0,00). Utvrđena je statistički pozitivna korelacija proinflamatornog hemerina i parametara insulinske rezistencije (glikoza nakon 2h r=0,29, P=0,00), insulin našte r=0,47, P=0,00, insulin nakon 2h r=0,24, P=0,03, HOMA- IR r=0,45, P=0,00 i MATSUDA indeksa r=-0,34, P=0,00, proaterogenog lipidskog statusa (TGL r=0,34, P=0,00, Apo B/ Apo A-I r=0,31, P=0,00, IA r=0,25, P= 0,02, Apo A-I r=-0,31, P=0,00, HDL- hol r=-0,27, P=0,01 i Apo B r=-0,26, P= 0,01) i parametara inflamacije (fibrinogen r=0,38, P=0,00 i hsCRP r=0,29, P=0,01). Obim vrata i odnos obima struka i kuka u ispitivanoj grupi gojaznih imali su statistički značajan trend porasta sa porastom stepena kardiometaboličkog rizika (39,3±4,5 cm vs 40,7±4 cm vs 42,5±4,6 cm i 0,9±0,9 vs 1±0,2 vs 1±0,8). Gojaznost i kardiometabolički sindrom su imali značajan doprinoseći faktor za nastanak poremećaja geometrije leve komore (16/53 vs 21/5; p 0,000, Phi 0,526), bez statistički značajne razlike u zastupljenosti poremećaja u odnosu na stepen kardiometaboličkog rizika (19/29 vs 21/25 vs 13/16, Χ =0,24). Rizik za nastanak poremećaja geometrije miokarda leve komore imali su ispitanici stariji od 40 godina nezavisno od pola i prisustva arterijske hipertenzije (Odds ratio 3,49 (0,99 - 12,22), p=0,04). Kod gojaznih ispitanika sa kardiometaboličkim sindromom koncentrični remodelnig je bio najčešći oblik geometrije miokarda leve komore (Grupa I 19/19, Grupa II 15/21, Grupa III 10/13, p=0,25). Parametri sistolne funkcije nisu se statistički značajno razlikovali između ispitivane i kontrolne grupe, dok su se parametri dijastolne funkcije miokarda leve komore u ispitivanoj grupi gojaznih u odnosu na kontrolnu grupu, statistički značajno razlikovali (e's 0,1±0,02 vs 0,12±0,02, p=0,000 i E/e'av 8,75±1,81 vs 6,64±1,08, p=0,000). Koncentrični remodeling i koncentrična hipertrofija leve komore u grupi gojaznih ispitanika statistički su značajno bili povezani sa insulinskom rezistencijom (insulin našte r=0,434, P=0,001), HOMA-IR r=0,419, P=0,012, MATSUDA r=-0,455, P=0,006) i proaterogenim lipidskim parametrima (TGL r=0,329 P=0,043), (HDL-hol r=-0,365, P=0,031); (IA r=0,354, P=0,037); (Apo A-I r=-0,373, P=0,027); (Apo B r=0,317, P=0,014); (Apo B/Apo A-I r=0,411, P=0,014). ZAKLJUČAK: Proinflamatorni adipokini hemerin i rezistin imaju značajno više vrednosti u grupi gojaznih u odnosu na grupu normalno uhranjenih ispitanika i pozitivno korelišu sa antropometrijskim parametrima, ultrasonografskim parametrima masno tkivnih depoa, sa parametrima insulinske rezistencije, proaterogenim lipidskim statusom i parametrima inflamatornog odgovora. Antropometrijski paremetri- obim vrata, odnos obima struka i kuka i indeks telesne mase imaju trend porasta sa porastom kardiometaboličkog sindroma u grupi gojaznih ispitanika. Gojaznost i kardiometabolički sindrom značajan su doprinoseći faktor za nastanak poremećaja geometrije miokarda leve komore. Rizik za nastanak poremećaja geometrije miokarda leve komore trostruko je veći kod ispitanika starijih od 40 godina, nezavisno od pola i prisustva arterijske hipertenzije. Koncentrični remodeling je najzastupljeniji oblik geometrije miokarda leve komore, dok ekscentrična hipertrofija nije dijagnostikovana kod ispitivane i kontrolne grupe. Proaterogeni lipidski profil, parametri insulinske rezistencije i proinflamatorni parametri su povezani sa koncentričnim remodelingom i koncentričnom hipertrofijom miokarda leve komore u grupi gojaznih ispitanika. Parametri dijastolne funkcije miokarda leve komore u ispitivanoj grupi gojaznih razlikuju se u odnosu na kontrolnu grupu normalno uhranjenih, dok kod parametara sistolne funkcije ova povezanost ne postoji.Obesity is one of the most important diseases of modern medicine in the group of chronic non-communicable diseases. The influence of increased body fat mass is especially important in the pathogenesis of cardiovascular diseases, with possible consequences for the occurrence of heart failure, coronary insufficiency and rhythm disorders. Disproportion in the effects of aggressive factors, mechanical factors due to weight gain, and functional factors due to disorders of adipokine secretion and present risk factors, make it difficult to prevent disorders on target organs. The very fact that obesity as a chronic disease leads to comorbidities in the heart, with the presence of traditional risk factors, focuses on the interaction of proinflammatory adipokines of dysfunctional adipose tissue and left ventricular myocardial geometry disorder in the first place. OBJECTIVE: To examine the relationship between the size of subcutaneous and visceral abdominal fat depots, circulating concentrations of chemerin and SFRP-5 and left ventricular myocardial geometry in obese patients with cardiometabolic syndrome, as well as to determine whether the increase in cardiometabolic syndrome contributes to higher frequency of geometric disorders in obese subjects. MATERIAL AND METHODS: The study included obese subjects, without any associated comorbidities, as well as healthy normally fed subjects matched by age and gender who made up the control group. Additionally, the examined group was divided into three subgroups according to the criteria for the existence of cardiometabolic syndrome. All subjects underwent anthropometric measurements, analysis of body composition components, laboratory analysis of blood samples on automated analytical systems, with determination of glucose metabolism parameters (basal and 2 hours during oral glucose tolerance test), lipids and lipoproteins and inflammation parameters. Serum concentrations of proinflammatory adipokine, chemerin, and resistin, and the anti-inflammatory adipokine SFRP-5, respectively, were determined by ELISA, Enzyme-linked immunosorbent Assay, manufactured by R&D Systems, Inc., Minneapolis, USA. Echocardiographic two-dimensional transthoracic examinations of the heart (2D, pulse, tissue and color Doppler) were performed on an ultrasound machine Vivid 9, manufactured by "General Electrics Co", using a low frequency probe of 2.5 MHz, while for ultrasonographic measurement of visceral and subcutaneous thickness adipose tissue used General Electric (GE) Logic 7. RESULTS: Obese subjects had statistically significantly higher values of proinflammatory adipokines chemerin and resistin compared to normally fed subjects in the control group (47.6 (41.4-54) vs 24.6 (16.8-32.4), P = 0.00) and resistin (4.73 (4.52-4.93) vs 3.75 (3.19-4.30), P = 0.00), while the values of anti-inflammatory SFRP-5 have no statistically significant difference. Obese subjects had a positive correlation of serum proinflammatory chemerin concentration with body mass index (r = 0.41, P = 0.00), waist circumference (r = 0.46, P = 0.00), hip circumference (r = 0.41 , P = 0.00), and FAT (kg) (r = 0.36, P = 0.00), with neck circumference (r = 0.26, P = 0.01) and with the percentage of adipose tissue FAT kg) (r = 0.28, P = 0.01). Also, obese subjects had a statistically positive correlation between chemerin and subcutaneous adipose tissue parameters (Max SFTa r = 0.35, P = 0.00), (Max SFTb r = 0.45, P = 0.00), (Max PFT r = 0.34, P = 0.00)) and intra-abdominal adipose tissue (r = 0.37, P = 0.00). A statistically positive correlation was found between proinflammatory chemerin and insulin resistance parameters (glucose after 2 hours r = 0.29, P = 0.00), insulin on an empty stomach r = 0.47, P = 0.00, insulin after 2h r = 0, 24, P = 0.03, HOMA-IR r = 0.45, P = 0.00 and MATSUDA index r = -0.34, P = 0.00, proatherogenic lipid status (TGL r = 0.34, P = 0.00, Apo B / Apo AI r = 0.31, P = 0.00, IA r = 0.25, P = 0.02, Apo AI r = -0.31, P = 0.00, HDL- chol r = -0.27, P = 0.01 and Apo B r = -0.26, P = 0.01) and inflammation parameters (fibrinogen r = 0.38, P = 0.00 and hs-CRP r = 0.29, P = 0.01). Neck circumference and waist-hip circumference relation in the examined group of obese had a statistically significant increase with increasing degree of cardiometabolic risk (39.3 ± 4.5 cm vs 40.7 ± 4 cm vs 42.5 ± 4.6 cm and 0 .9 ± 0.9 vs 1 ± 0.2 vs 1 ± 0.8). Obesity and cardiometabolic syndrome had a significant contributing factor to the development of left ventricular geometry disorders (16/53 vs 21/5; p 0.000, Phi 0.526), without a statistically significant difference in the prevalence of disorders in relation to the degree of cardiometabolic risk (19/29 vs 21 / 25 vs 13/16, Χ = 0.24). Examinees older than 40 years, regardless of gender and the presence of arterial hypertension, had a risk of developing left ventricular geometry disorders (Odds ratio 3.49 (0.99 - 12.22), p = 0.04). In obese subjects with cardiometabolic syndrome, concentric remodeling was the most common form of left ventricular myocardial geometry (Group 1: 19/19, Group 2: 15/21, Group 3: 10/13, p = 0.25). Statistical difference between the parameters of systolic function was insignificant between the examined and control groups, while statistical difference between the parameters of left ventricular myocardial diastolic function in the examined group of obese compared to the control group was significant (e's 0.1 ± 0.02 vs 0.12 ± 0.02, p = 0.000 and E / e'av 8.75 ± 1.81 vs 6.64 ± 1.08, p = 0.000). Concentric remodeling and concentric left ventricular hypertrophy in the group of obese subjects were statistically significantly associated with insulin resistance (insulin on an empty stomach r = 0.434, P = 0.001), HOMA-IR r = 0.419, P = 0.012, MATSUDA r = -0.455, P = 0.006), proatherogenic lipid parameters (TGL r = 0.329 P = 0.043), (HDL-chol r = -0.365, P = 0.031); (IA r = 0.354, P = 0.037); (Apo A-I r = -0.373, P = 0.027); (Apo B r = 0.317, P = 0.014); (Apo B / Apo A-I r = 0.411, P = 0.014). CONCLUSION: Proinflammatory adipokines chemerin and resistin have significantly higher values in the group of obese compared to the group of normally fed subjects and are positively correlated with anthropometric parameters, ultrasonographic parameters of adipose tissue depots, with insulin resistance parameters, proatherogenic lipid status and parameters of inflammatory response. Anthropometric parameters - neck circumference, waist and hip circumference relation and body mass index have an increasing trend with an increase in cardiometabolic syndrome in the group of obese subjects. Obesity and cardiometabolic syndrome are significant contributing factors to the development of left ventricular myocardial geometry disorders. The risk of developing left ventricular myocardial geometry disorders is three times higher in examinees older than 40, regardless of gender and the presence of arterial hypertension. Concentric remodeling is the most common form of left ventricular myocardial geometry, while eccentric hypertrophy has not been diagnosed in the study and control groups. Proatherogenic lipid profile, insulin resistance parameters, and proinflammatory parameters are associated with concentric remodeling and concentric left ventricular myocardial hypertrophy in a group of obese subjects. The parameters of diastolic function of the left ventricular myocardium in the examined group of obese people differ in relation to the control group of normally fed, while in the parameters of systolic function this connection does not exist