Cardiac allograft vasculopathy (CAV) is a unique form of accelerated atherosclerosis in heart transplant recipients that limits long-term survival. The pathophysiology of CAV is not fully clear, but is likely to be mulitfactorial with a range of immunological and non-immunological contributors. The aims of this thesis were to investigate the prognostic significance of both immunological and non-immunological markers of CAV. Paper I examines the role of the neurohormonal biomarker, NT-proBNP, and the inflammatory biomarker, CRP, in identifying patients at higher risk of CAV and cardiac mortality. Paper II explores the prognostic significance of impaired renal function following heart transplantation and the associated risk of CAV and mortality. In paper III, the role of chronic infection with the parasite T.gondii is investigated in relation to CAV. Finally, in paper IV, intravascular ultrasound is employed with parallel measurement of a broad range of inflammatory biomarkers to help allow identification of novel markers of CAV. The findings of this thesis demonstrate that both immunological and non-immunological markers can be utilized to accurately identify patients at higher risk of developing CAV and routine measurement in clinical practice could, potentially, help improve long-term survival following heart transplantation.
LIST OF PAPERS
Paper I: Probrain natriuretic peptide and C-reactive protein as markers of acute rejection, allograft vasculopathy, and mortality in heart transplantation. Arora S, Gullestad L, Wergeland R, Simonsen S, Holm T, Hognestad A, Ueland T, Geiran O, Andreassen A. Transplantation. 2007 May 27;83(10):1308-1315. DOI: 10.1097/01.tp.0000263338.39555.21
Paper II: Prognostic importance of renal function 1 year after heart transplantation for all-cause and cardiac mortality and development of allograft vasculopathy. Arora S, Andreassen A, Simonsen S, Gude E, Dahl C, Skaardal R, Hoel I, Geiran O, Gullestad L. Transplantation 2007 Jul 27;84(2):149-154. DOI: 10.1097/01.tp.0000268810.61393.2c
Paper III: Pre-transplant Toxoplasma gondii seropositivity among heart transplant recipients is associated with an increased risk of all-cause and cardiac mortality. Arora S, Jenum PA, Aukrust P, Rollag H, Andreassen AK, Simonsen S, Gude E, Fiane AE, Geiran O, Gullestad L. J Am Coll Cardiol. 2007 Nov 13;50(20):1967-1972. DOI: 10.1016/j.jacc.2007.07.068
Paper IV: Arora S, Gunther A, Wennerblom B, Ueland T, Andreassen AK, Gude E, Geiran O, Wilhelmsen N, Endresen K, Andersen R, Aukrust P, Gullestad L. Systemic markers of inflammation are associated with advanced cardiac allograft vasculopathy and an increased inflammatory component. Submitted. Am J Transplant (Wiley) 2010 Jun;10(6):1428-36. DOI: 10.1111/j.1600-6143.2010.03118.x