Bass Rosara, Stalvey Michael, Solomon George, Rowe Steven, Nichols David, Schwarzenberg Sarah Jane, Freedman Steven, Walega Rachel, Kelly Andrea
Ohio State University and Nationwide Children's Hospital, Columbus, OH, USA.
University of Alabama at Birmingham, Birmingham, AL, USA.
J Clin Transl Endocrinol. 2025 Apr 2;40:100391. doi: 10.1016/j.jcte.2025.100391. eCollection 2025 Jun.
BACKGROUND/AIMS: 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.
METHODS/RESULTS: 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.
背景/目的：囊性纤维化患者（PwCF）的总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平较低（TC、HDL-C和LDL-C），且历来心血管疾病患病率较低。最近，有报道称PwCF患者出现急性心肌梗死病例。依列卡福-替扎卡福-依伐卡福（ETI）对胆固醇和甘油三酯（TG）浓度以及传统心脏代谢危险因素的影响尚不清楚。
方法/结果：对参与观察性PROMISE研究的参与者在开始临床处方ETI之前以及开始后12 - 18个月的TC、LDL-C、HDL-C和TG浓度进行了分析。比较了ETI治疗前和随访时的浓度，并使用线性混合效应模型测试了TC、LDL-C、HDL-C和TG与临床因素之间的关系。51名参与者（25名男性/26名女性，中位年龄17.4岁）在基线时以及ETI开始后12 - 18个月有空腹样本，这些参与者存在胰腺外分泌功能不全。在未调整模型中，ETI治疗12 - 18个月后TC和HDL-C较高，但在调整BMI-Z后，随访时只有HDL-C仍显著较高（p < 0.05）。HDL-C低是最常见的异常情况（>50%）），但符合HDL-C低标准的参与者在不同时间点的患病率没有差异。
在患有囊性纤维化的青年和年轻成年人中，ETI治疗12 - 18个月后TC和HDL-C较高，但在调整BMI-Z后TC的差异减弱。两个时间点HDL-C低的患病率都很高。
