Cardiometabolic risk factors in individuals with cystic fibrosis undergoing Elexacaftor/Tezacaftor/Ivacaftor therapy

<bold>Objectives:</bold> In light of the increased survival age, concerns have been raised regarding potential cardiovascular risk in people with cystic fibrosis (pwCF) undergoing Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy. This study aimed to evaluate changes in selected cardiometabolic risk factors in pwCF receiving ETI. <bold>Methods:</bold> This prospective study included pwCF initiating ETI between January 2021 and June 2022 at the adult CF centre of Milan. BMI, glycemia, lipid profile, and inflammatory biomarkers were measured before treatment initiation and at one- and six-month post-therapy. Mean values and 95% confidence intervals at study time points were estimated using generalized estimating equations with an autoregressive correlation structure. <bold>Results:</bold> 59 patients were enrolled (mean age 40.6,21-54). Over the study period, a significant reduction was detected in CRP (from 3.33mg/L at treatment initiation to 0.60 after one month and 0.65 after 6 months, p<0.001) and IL-6 (from 4.26 pg/mL to 1.97 and 2.67,p<0.001). Furthermore, there was a significant increase in BMI (from 21.6 kg/m2 to 21.9 and 22.4, p<0.001), leptin (from 2.38 ng/mL to 2.71 and 3.23, p=0.006), triglycerides (from 92mg/dL to 110 and 108, p<0.001), total cholesterol (from 171 mg/dL to 185 and 194, p<0.001),LDL (from 93mg/dL to 100 and 106, p=0.001), and apolipoproteinB (from 81mg/dL to 85 and 87 p=0.018). No significant changes were observed for fasting glycemia,HDL,HOMA-IR and PCSK9. <bold>Conclusions:</bold> After six months of ETI treatment, mean values of several cardiometabolic risk factors increased. Further studies are needed to understand the implications of these findings on the cardiovascular risk of pwCF.