Arterial stiffness as a marker of vascular aging in IBD patients

Abstract

Kronične upalne bolesti crijeva (IBD) povezane su s preuranjenom aterosklerozom uzrokovanom disfunkcijom endotela i povećanjem intime-medije krvnih žila. Upravo u stanjima kronične sustavne upale, kao što je IBD, kroz prisutnost dislipidemije i ubrzane ateroskleroze u sklopu podležećeg upalnog procesa dolazi do povišene krutosti velikih arterija. Uloga krutosti arterija u razvoju kardiovaskularnih bolesti dobro je poznata, a određivanje krutosti arterija sve se više upotrebljava u kliničkoj praksi u svrhu procjene kardiovaskularnog rizika u bolesnika, te je jedan od pokazatelja vaskularnog starenja. Neinvazivno mjerenje brzine pulsnog vala aorte (eng. pulse wave velocity, PWV) i augmentacijskog indeksa (Aix) ima prediktivnu vrijednost za otkrivanje budućih fatalnih kardiovaskularnih incidenata, kao i za ukupni kardiovaskularni rizik. Ovim istraživanjem utvrđeno je kako gotovo polovica svih ispitanika (54(45%)) ima povišenu vrijednost PWV, odnosno prisutno supkliničko oštećenje ciljnih organa. U našoj kohorti IBD bolesnika nije bilo razlika u markerima krutosti arterija između pacijenata s ulceroznim kolitisom i Crohnovom bolešću, kao ni u ovisnosti o fenotipu, lokalizaciji bolesti ili primijenjenoj terapiji. Prisutnost povišene PWV (>8 m/s, 45% bolesnika) najprevalentniji je marker supkliničkog oštećenja ciljnih organa u našoj kohorti IBD bolesnika, a PWV raste s dobi te postaje viši u odnosu na kontrolnu skupinu ispitanika s dobro liječenom arterijskom hipertenzijom. Ubrzano vaskularno starenje rezultat je produljenog trajanja IBD kao vjerojatnog uzroka povišene PWV, a bolesnici su imali i povišen Aix, kao marker povišene krutosti arterija srednje velikih i malih arterija. U svim skupinama bolesnika upravo su dob i duljina trajanja IBD bili snažni, neovisni prediktori povišene PWV. Ovi rezultati pokazuju da IBD s prisutnom kroničnom, sustavnom upalom ima sličnu ulogu u razvoju ubrzane ateroskleroze, povišene krutosti arterija i supkliničkog oštećenja ciljnih organa, kao i arterijska hipertenzija, etablirani rizični faktor za povišenu krutost arterija. Također, može se zaključiti da je porast krutosti arterija i ubrzano vaskularno starenje više izraženo u onih bolesnika s duljim trajanjem IBD. Naši rezultati povišene PWV i Aix u pacijenata s duljim trajanjem IBD govore u prilog činjenici da je kronična sustavna upala odgovorna za promjene u velikim i malim arterijama i dovodi do oštećenja ciljnih organa u ovih bolesnika, neovisno o trenutnom statusu aktivnosti bolesti. Preuranjena ateroskleroza i prisutnost dislipidemije moraju biti adekvatno nadzirane i liječene, posebice u onih IBD bolesnika s duljim trajanjem bolesti.Chronic inflammatory bowel diseases (IBD) are associated with premature atherosclerosis caused by endothelial dysfunction and increased arterial intima-media. In conditions characterized by chronic systemic inflammation, like IBD, chronic inflammatory process through dyslipidemia and accelerated atherosclerosis leads to increase in arterial stiffness of the large arteries. The crucial role of arterial stiffness in the development of cardiovascular disease is well known and arterial stiffness measurement is increasingly being used for cardiovascular risk assessment and it is an indicator of vascular aging. Non-invasive measurement of pulse wave velocity (PWV) and augmentation index (Aix) has predictive value for future fatal cardiovascular events and overall cardiovascular risk. In our research, nearly half of the examinees had increased PWV (45%) and subclinical target organ damage. There were no differences in arterial stiffness markers in Crohn's disease (CD) and ulcerative colitis (UC) patients. Also, patients divided according to disease phenotype, localization and applied therapy showed no differences in PWV and Aix markers. Increased PWV (>8m/s) is the most prevalent marker of subclinical target organ damage in our IBD patient cohort. We also showed that PWV increases with age and becomes higher than PWV in the control group of examinees with well-controlled arterial hypertension. Accelerated vascular aging is the result of prolonged duration of IBD as the most plausible cause of increased PWV. Patients also had increased Aix as a marker of increased arterial stiffness of medium and small arteries. Age and duration of IBD were strong and independent predictors of increased PWV in all groups of IBD patients. These results show that IBD with chronic, systemic inflammation plays a role in the development of accelerated atherosclerosis, increased arterial stiffness and subclinical target organ damage similar to arterial hypertension, an established risk factor for arterial stiffness. Also, we can conclude that increased arterial stiffness and accelerated vascular aging are more pronounced in those patients with a more prolonged duration of IBD. Our results of increased PWV and Aix in IBD patients with longer disease duration are contributing to the fact that chronic inflammation is responsible for alterations of both large and smaller arteries and leads to target organ damage in these patients, regardless of current disease activity. Premature atherosclerosis and dyslipidemia should be closely monitored and treated, especially in IBD patients with longer disease duration