Work

Cholesterol and triglyceride concentrations following 12–18 months of clinically prescribed elexacaftor-tezacaftor-ivacaftor—PROMISE sub-study

Year: 2025

Type: article

Abstract: • The impact of ETI on cholesterol and triglyceride concentrations, traditional cardiometabolic risk factors, is unknown. • Cholesterol and triglyceride levels were examined prior to and after 12–18 months of ETI. • Total and HDL cholesterol concentrations were higher after 12–18 months of ETI as compared to baseline. • Differences in total cholesterol seen with ETI were attenuated with adjustment for BMI-Z. People with CF (PwCF) have low total, high, and low density lipoprotein cholesterol (TC, HDL-C and LDL-C) and historically have had low prevalence of cardiovascular disease. More recently, cases of acute myocardial infarction are reported in PwCF. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on cholesterol and triglyceride (TG) concentrations, traditional cardiometabolic risk factors, is unknown. TC, LDL-C, HDL-C, and TG concentrations were analyzed from participants enrolled in the observational PROMISE study of clinically prescribed ETI prior to and 12–18 months after initiation. Pre-ETI and follow-up concentrations were compared, and relationships between TC, LDL-C, HDL-C and TG and clinical factors were tested using linear mixed-effect models. Fasting samples were available for 51 participants (25 M/26F, median age 17.4 y) with pancreatic exocrine insufficiency at baseline and 12–18 months after ETI initiation. TC and HDL-C were higher after 12–18 mo ETI in an unadjusted model, but with adjustment for BMI-Z, only HDL-C remained significantly higher at follow up (p < 0.05). Low HDL-C was the most common abnormality (>50 %), but prevalence of participants meeting criteria for low HDL-C did not differ between timepoints. In a population of youth and young adults with CF, TC and HDL-C were higher after 12–18 months of ETI, but differences in TC were attenuated with adjustment for BMI-Z. Prevalence of low HDL-C was high at both timepoints.

Source: Journal of Clinical & Translational Endocrinology

DOI: 10.1016/j.jcte.2025.100391