Plasma PCSK9 levels in children and adolescents: evidence from an Italian outpatient paediatric clinic cohort at cardio-metabolic risk

BACKGROUND AND AIM Whether measuring circulating PCSK9 plasma levels in cardiovascular contexts may be of use in the clinical practice remains uncertain. The aim of the present study was to investigate PCSK9 levels in a cohort of children and adolescents referred to a paediatric outpatient clinic for cardio-metabolic risk assessment. METHODS AND RESULTS 332 children and adolescents were recruited between December 2014 and June 2024. Plasma PCSK9 enzyme-linked immunosorbent assay, glucose, insulin, fasting lipids, and uric acid were assessed, with calculation of non-HDL cholesterol, remnant cholesterol, and homeostasis model assessment index. The median age was 11.2 years, with 44.1% having initiated pubertal development, 81.9% were classified as excess weight and 16.3% as hypertensive. The median PCSK9 levels were 187.2 ng/mL. After adjustment for age and BMI z-score, the presence of lipid values above the clinical threshold was significantly associated with higher PCSK9 levels (p<0.01) : total cholesterol ≥200 mg/dL (+51.7 ng/mL), non-HDL-C ≥ 145 mg/dL (+43.6 ng/mL), remnant-cholesterol ≥30 mg/dL (+49.6 ng/mL), LDL-C ≥ 130 mg/dL (+34.1 ng/mL), and triglycerides above cut-offs (+49.2 ng/mL). Similarly, a positive parental history of dyslipidaemia was significantly associated with higher PCSK9 values (+39.9 ng/mL) (p<0.001). CONCLUSIONS In a cohort of children and adolescents at cardio-metabolic risk, circulating PCSK9 levels were significantly associated with atherogenic lipid fractions, including LDL-C, non-HDL-C, triglycerides, and remnant cholesterol. These findings suggest that PCSK9 may play a broader role in lipid metabolism beyond LDL-C regulation, particularly in relation to triglyceride-rich lipoproteins.