| Abstract | Osobe koje su preživjele malignu bolest u djetinjstvu imaju značajno veći pobol i smrtnost od kardiovaskularnih bolesti u odrasloj dobi. Antraciklini su lijekovi s izrazitom toksičnošću za kardiovaskularni sustav i najznačajniji su uzrok kardiovaskularnih događaja u preživjelih. Kardiotoksičnost antraciklina je dobro poznata, ali do sada nije istraživan njihov učinak na krutost arterija u djece. Krutost arterija je nezavisni prediktor kardiovaskularnih bolesti. Cilj istraživanjaCilj ove studije bio je odrediti mogu li antraciklini primijenjeni u liječenju maligne bolesti u djetinjstvu povećati krutost arterija mjerenu kao brzina širenja pulsnog vala u aorti (PWVao) i augmentacijski indeks aorte (AIxao). Osim toga, cilj je bio utvrditi koji klinički parametri koreliraju s brzinom širenja pulsnog vala i koja je granična vrijednost PWVao između zdravih i bolesnih. Ispitanici i metodePregledano je 119-ero djece i adolescenata u dobi od 7 do 20 godina, od toga 69-ero djece i adolescenata (srednja dob 13,69±4,45 godina) u kojih je liječenje maligne bolesti antraciklinima, prema različitim protokolima, završeno prije najmanje godinu dana. Pacijenti su bili bez kliničkih i laboratorijskih znakova maligne ili srčane bolesti. Kontrolnu skupinu sačinjavalo je 50-ero zdrave djece i adolescenata (srednja dob v 12,68±3,22 godina). Krutost arterija je određena mjerenjem brzine širenja pulsnog vala u aorti (PWVao) te augmentacijskog indeksa aorte (AIxao) oscilometrijskom metodom uređajem Arteriograph TensioMed. RezultatiU ispitanika koji su liječeni antraciklinima PWVao je bio značajno veći u usporedbi s kontrolnom skupinom (6,25±1,31 m/s vs 5,64±0,66 m/s; P<0,001). Augmentacijski indeks aorte (AIxao) bio je također veći u skupini pacijenata nego u zdravih (8,7±9,69% vs 5,64±5,15%; P=0,044). Univarijatnom analizom je u skupini pacijenata nađena pozitivna korelacija PWVao s dobi, tjelesnom visinom i težinom, krvnim tlakom, srčanom frekvencijom, srednjim arterijskim tlakom i centralnim aortnim tlakom. Nije nađena korelacija PWVao s visinom doze antraciklina niti vremenom koje je proteklo od završetka liječenja. Glavni prediktori brzine širenja pulsnog vala nakon multivarijatne regresijske analize su tjelesna visina, srčana frekvencija i tjelesna aktivnost. Granična vrijednost za PWVao je 6,25 m/s (95 CI 0,591-0,765; P < 0,001; osjetljivost 44,9% i specifičnost 90%). Zaključak Brzina širenja pulsnog vala u aorti (PWVao) i augmentacijski indeks aorte (AIxao) su značajno veći u pacijenata liječenih antraciklinima prije godinu dana i više u odnosu na zdravu djecu. Moguće je da učinak antraciklina na kasnu smrtnost u osoba liječenih u djetinjstvu zbog maligne bolesti nije povezan samo s kardiotoksičnosti, nego i s povećanom krutosti arterija. |
| Abstract (english) | Survivors of childhood malignancy have a significantly higher cardiovascular morbidity and mortality later in life. Anthracyclines are associated with marked cardiovascular toxicity and are therefore the major cause of cardiovascular events in this population group. Anthracyclines cardiotoxicity is well known, however, their effect on arterial stiffness has not yet been investigated in children. Arterial stiffness is an independent predictor of cardiovascular disease.Aim of the study The aim of the study was to determine whether anthracyclines used for the treatment of malignant disease in childhood could increase arterial stiffness measured as the aortic pulse wave velocity (PWVao) and aortic augmentation index (AIxao). In addition, the aim was to identify the clinical parameters correlating with PWVao and the cutoff PWVao value discriminating healthy and diseased subjects. Subjects and methods A total of 119 children and adolescents aged 7-20 years were examined, 69 of them (mean age 13.69±4.45 years) having completed anthracycline therapy for vii malignant disease according to various protocols at least a year before. Study patients were free from clinical and laboratory signs of malignant or cardiac disease. Control group included 50 healthy children and adolescents, mean age 12.68±3.22 years. Arterial stiffness was determined by measuring PWVao and AIxao using oscillometric method on an Arteriograph TensioMed device. ResultsPWVao was significantly higher (6.25±1.31 m/s vs 5.64±0.66 m/s; P<0.001) and AIxao was higher (8.7±9.69% vs 5.64±5.15%; P=0.044) in subjects with a history of anthracycline treatment as compared with control group. Univariate analysis yielded positive correlation of PWVao with age, body weight, body height, blood pressure, heart rate, mean arterial pressure and central arterial pressure in the group of patients previously treated with anthracyclines. There was no correlation of PWVao with anthracycline dosage and time elapsed from treatment completion. Multivariate regression analysis indicated body height, heart rate and physical activity to be the main PWVao predictors. The cutoff value of PWVao was 6.25 m/s (95%CI 0.591-0.765; P<0.001; sensitivity 44.9%; specificity 90%). Conclusion PWVao and AIxao are significantly higher in patients treated a year or more before with anthracyclines as compared to healthy children. The effect of anthracyclines on late mortality in individuals treated for malignant disease in childhood may not be exclusively due to their cardiotoxicity, but also to the increased arterial stiffness. |
