Sex differences in lipid profile and response to statin treatment in pediatric patients affected by familial hypercholesterolemia

Differences between males and females in lipid profile are observed in distribution and trajectory during pediatric age and are more pronounced in hereditary lipid disorders such as familial hypercholesterolemia when absolute cholesterol levels are higher from birth onwards. A retrospective observational study was undertaken to explore the sex differences in lipid profiles of pediatric patients affected by heterozygous form of familial hypercholesterolemia (FH) and treated with statins. A cohort of 322 pediatric patients, aged 2-17 years, diagnosed with heterozygous FH and regularly followed in Rare Disease and Medical Genetics Unit of the Bambino Gesù Children's Hospital of Rome (Italy) from 2015-2024, was enrolled in this study. A subgroup of 112 patients, aged 8-17 years, was treated with statins. For all patients, the lipid profile was assessed at diagnosis. For patients treated with statins, the lipid profile was assessed at diagnosis and after 1 year of statin therapy. Differences between males and females in lipid profile were observed in the subgroup of patients aged 8-17 years. Females had significantly (p < 0.05) higher TC, LDL-C and TG plasma values than males, and clinically they respond better to statin treatment. CONCLUSION: Personalized therapy, accounting for these differences, could enhance treatment outcomes and optimize long-term cardiovascular health in affected children. WHAT IS KNOWN: • Familial hypercholesterolemia (FH) is characterized by elevated plasma level of total cholesterol from the birth. • If left untreated, FH can lead to premature atherosclerotic cardiovascular disease, and young female with FH are at high risk of developing it. • FH girls have higher levels of TC, LDL-C, and TG plasma values levels than boys in a previous study and this may contribute significantly to the total lifelong cholesterol burden in FH women. WHAT IS NEW: • Significant sex differences in lipid profile were confirmed in heterozygous FH (HeFH) patients aged 8-17 years: females had significantly higher TC, LDL-C and TG plasma values than males. • Early statin treatment in children with FH, and girls in particular, may impact cholesterol burden in FH patients.