INTRODUCTION:
Familial hypercholesterolemia (FH) is an inherited condition marked by elevated LDL cholesterol and increased cardiovascular risk, with many patients failing to achieve LDL-C goals despite treatment. Physical activity and exercise may offer cardiovascular protection by enhancing fitness and modulating inflammatory and metabolic processes. The UPPA-FH study 1) examines the relationships between physical activity and fitness with subclinical atherosclerosis and metabolomic profiles in FH, and 2) evaluates the effects of high intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercise training on fitness and, atherosclerosis-related outcomes. This abstract presents the study protocol and preliminary fitness results versus reference values.
METHODS:
The UPPA-FH study includes two complementary designs. For aim 1, a cross-sectional study will be conducted in 200 patients with FH from Granada and Almeria. Accelerometer-measured physical activity, cardiorespiratory fitness (CRF), muscular strength, markers of subclinical atherosclerosis, and metabolomic profiles will be assessed. For aim 2, a 16-week parallel-group randomized controlled trial will be conducted in 75 participants (n=25 per group) allocated to: HIIT (4 intervals of 4 minutes at 85–95% of maximal heart rate, 3 days/week), MICT (34 minutes at 69–76% of maximal heart rate, 3 days/week) or usual care. CRF will be assessed with the modified Bruce test; muscular strength with the handgrip and 30-second chair stand tests; vascular outcomes with PET/CT, 24 h pulse wave monitoring, and carotid ultrasound; and metabolomics by nuclear magnetic resonance spectroscopy. So far, 81 adults with FH (30 men and 51 women; mean age 50.1 +/- 13.1 years) have participated in the cross-sectional study. CRF (maximal oxygen uptake; VO2max) and muscular strength were compared with age- and sex-matched reference values [1-3]. Pre- and post-intervention assessments (two visits each) will replicate baseline measurements.
RESULTS:
In the CRF test, women scored an average at the 66.5th percentile and men at the 54.8th percentile compared with reference values. In the handgrip strength test, women scored an average at the 32.9th percentile and men at the 34.0th percentile relative to global reference values. In the 30-second chair stand test, 41.2% of women and 33.3% of men reached the minimum functional threshold.
CONCLUSION:
Discussion and conclusion: Patients with FH exhibited below-average muscular strength but average CRF. Women demonstrated higher CRF percentiles than men, whereas handgrip strength percentiles were similarly low in both sexes. Ongoing analyses will clarify the role of physical activity, exercise, and fitness in FH management.
References:
1. Kaminsky, Imboden, Arena et al. Mayo Clin Proc. 2017;92(2):228– 233.
2. Tomkinson, Lang, Rubín et al. J Sport Health Sci. 2024;14: 101014.
3. McKay, Baldwin, Ferreira et al. Neurology. 2017;88(16):1512-1519.