Key result
Pediatric HeFH therapy is linked to higher YKL-40 levels, but shows no difference in other inflammatory markers.
Why the study?
In pediatric familial hypercholesterolemia, the inflammatory phenotype, its role in cardiovascular risk stratification, and its alterations under lipid-lowering therapy remain poorly understood.
Does pharmacological lipid-lowering therapy with statins ± ezetimibe alter systemic inflammatory profiles and their associations with metabolic parameters in pediatric patients with heterozygous familial hypercholesterolemia?
Cross-Sectional (n=65)
Does pharmacological lipid-lowering therapy with statins ± ezetimibe alter systemic inflammatory profiles and their associations with metabolic parameters in pediatric patients with heterozygous familial hypercholesterolemia?
Pediatric heterozygous familial hypercholesterolemia patients treated with statins ± ezetimibe may have persistent macrophage activation indicated by elevated YKL-40 levels despite lipid-lowering therapy.
No immediate change to pediatric HeFH management; hypothesis-generating for YKL-40 as residual-risk marker needing longitudinal validation.
INTRODUCTION: Excess LDL-cholesterol and chronic inflammation accelerate atherosclerosis in familial hypercholesterolemia (FH). In pediatric FH, the inflammatory phenotype, its role in cardiovascular risk stratification and its alterations under lipid-lowering therapy remain poorly understood. Therefore, we comprehensively profiled systemic inflammatory markers in pediatric heterozygous FH (HeFH) under different treatment modalities and investigated associations with liver enzymes and lipid parameters. METHODS: For this exploratory cross-sectional study, we prospectively enrolled 49 children with HeFH grouped as newly diagnosed, treatment-naïve (n = 11), diet-treated (n = 10) and pharmacologically treated with statins ± ezetimibe (n = 28), and 16 unaffected controls (overall median age 11 years; 58.8% female). Fasting blood samples were analyzed for routine laboratory parameters and quantification of 37 inflammatory markers using a multiplex immunoassay. RESULTS: While traditional inflammatory markers (CRP, IL-6) did not differ between groups, the macrophage activation marker chitinase-3-like protein 1 (YKL-40) was nominally elevated in pharmacologically treated patients vs. controls (p = 0.037). In this subgroup, markers of tissue remodelling and bone metabolism (osteopontin, osteocalcin) as well as immune activation (sCD30, sCD163) showed robust correlations with alkaline phosphatase and liver enzymes. Additionally, soluble TNF receptor 2 correlated inversely with HDL-cholesterol (r = -0.574, p = 0.009) and apolipoprotein A1 (r = -0.607, p = 0.009). CONCLUSION: In conclusion, pediatric HeFH patients receiving pharmacological therapy may exhibit persistent, potentially atherogenic macrophage activation reflected by elevated YKL-40 despite effective lipid lowering. The observed associations between immune markers and hepatic and bone metabolic parameters suggest pleiotropic effects of statins ± ezetimibe independent of lipid lowering.
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Mair et al. (2026) conducted a cross-sectional in Pediatric heterozygous familial hypercholesterolemia (HeFH) (n=65). Pharmacological lipid-lowering therapy (statins ± ezetimibe) vs. Unaffected controls, treatment-naïve, and diet-treated HeFH patients was evaluated on Systemic inflammatory markers including chitinase-3-like protein 1 (YKL-40) (p=0.037). Pharmacological therapy (statins ± ezetimibe) in pediatric HeFH was associated with nominally elevated YKL-40 compared to controls (p = 0.037), while CRP and IL-6 did not differ.
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