Micro‐ and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients—An exploratory study

Background Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro‐ and macrovascular CAV and major adverse cardiac events in HTx patients. Methods We evaluated 91 cardiovascular disease‐related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro‐ and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O‐H 2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death. Results We found consistent differences in two proteins involved in cholesterol homeostasis: significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) ( p < .05) and significantly decreased paraoxonase 3 (PON3) ( p < .05). N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was significantly increased in patients with microvascular CAV ( p < .05) and borderline significantly increased in patients experiencing major adverse cardiac events ( p = .10) and patients with macrovascular CAV ( p = .05). Conclusions We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT‐proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.