Work

High-intensity interval training and moderate-intensity continuous training versus usual care in adults with familial hypercholesterolaemia: protocol for the UPPA-FH three-arm randomised trial

Year: 2026

Type: article

Abstract: Introduction Familial hypercholesterolaemia (FH) is an inherited disorder associated with lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-c) and substantially increased risk of premature atherosclerotic cardiovascular disease. Although intensive lipid-lowering therapy is the cornerstone of management, many individuals remain at elevated residual cardiovascular risk. Exercise training may improve cardiorespiratory fitness (CRF), vascular function and cardiometabolic health; however, randomised evidence comparing different exercise modalities in adults with FH is lacking. The UPPA-FH trial aims to evaluate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), compared with usual care, on CRF, subclinical atherosclerosis and cardiometabolic health in adults with FH. Methods and analysis The UPPA-FH is a single-centre, three-arm, parallel-group superiority randomised controlled trial. 75 adults with genetically confirmed FH will be randomly allocated (1:1:1) to 16 weeks of supervised HIIT, supervised MICT or usual care. The primary outcome is change in maximal oxygen uptake (VO₂max) from baseline to 16 weeks, measured by cardiopulmonary exercise testing. Key secondary outcomes include markers of subclinical atherosclerosis (vascular inflammation, carotid intima-media thickness), arterial stiffness, biomarkers of cardiometabolic health (inflammation, oxidative stress, endothelial dysfunction and lipid metabolism), as well as body composition, physical function and estimated cardiovascular risk. The primary analyses will be conducted in the intention-to-treat population using a mixed model for repeated measures, adjusted for baseline outcome values and prespecified covariates. Treatment effects will be presented as adjusted between-group differences with corresponding 95% CIs. Confirmatory treatment comparisons will follow a prespecified fixed-sequence hierarchical testing procedure: (1) HIIT versus usual care; (2) MICT versus usual care and (3) HIIT versus MICT. Each comparison will be tested using a two-sided significance level of 0.05. Ethics and dissemination The study has been approved by the Biomedical Research Ethics Committee of Granada (reference 1417 N-23). Results will be disseminated through peer-reviewed publications, scientific conferences and communication with healthcare professionals and patient organisations. Trial registration number NCT06833944. Version date and identifier Version 2.0 (12 July 2026).

Source: BMJ Open

DOI: 10.1136/bmjopen-2025-114501