BACKGROUND: Cystic fibrosis (CF) has been associated with impaired cardiovascular and endothelial function. CF transmembrane conductance regulator (CFTR) modulator therapy, most recently Elexacaftor/Tezacaftor/Ivacaftor (ETI), has led to improved CFTR function and life expectancy. However, the rising prevalence of obesity in adults is concerning. This study assessed the micro- and macrovascular endothelial function, cardiovascular disease (CVD) risk factors, and physical activity (PA) profiles in people with CF (pwCF) on ETI compared to healthy matched controls. METHODS: In 15 pwCF and 15 age- and sex-matched controls, microvascular endothelial function (via transdermal delivery of insulin [INS] and acetylcholine [ACh] on the forearm), macrovascular endothelial function (via flow-mediated dilation [FMD] of the brachial artery), central haemodynamic parameters, including heart rate (HR), stroke volume index (SVi) and cardiac output index (Q̇I) (via thoracic impedance cardiography), body mass index (BMI), blood pressure (BP), and accelerometer-assessed PA were measured. RESULTS: There were no differences in INS or FMD-mediated vasodilation between the groups (P >
0.05). However, a reduced vasodilatory response was evident in pwCF following ACh-mediated vasodilation (P = 0.01) and FMD normalised for shear rate (P = 0.03). No differences in resting HR, SVi, Q̇I, BP, BMI or PA were found (P >
0.05). CONCLUSION: This study demonstrated reduced micro- and macrovascular function in pwCF. This dysfunction may have potential health implications, particularly regarding long-term cardiovascular risk and further longitudinal assessments are warranted.