Comprehensive risk calculator for children with heterozygous familial hypercholesterolemia

Introduction. Heterozygous familial hypercholesterolemia (HeFH) is the most common inherited disorder of lipid metabolism, characterized by a high risk of early cardiovascular events.

Aim. To develop and validate a multidimensional prognostic algorithm for predicting the presence of subclinical atherosclerosis (defined as intima-media thickness (IMT) > 95th percentile for age and sex or the presence of at least one carotid atherosclerotic plaque) in children with HeFH, and thereafter use this algorithm as a risk calculator to personalize lipid-lowering therapy.

Materials and methods. A retrospective, single-center, cross-sectional study was conducted at the Children's Cardiology Center of the Bashlyaeva Children’s City Clinical Hospital of Moscow Health Department (Moscow). The study included 374 patients between ages 6 and 18. Based on the Simon Broom criteria, the diagnosis of FH referred to either definite or possible heterozygous FH. Common carotid intima-media thickness (CIMT) measurement and atherosclerotic plaque detection were recognized as validated surrogate markers of increased cardiovascular risk. Ultrasound findings of subclinical atherosclerosis (IMT > 95th percentile and/or the presence of atherosclerotic plaques) were used as the study outcome.

Results. The resulting model demonstrated good discriminatory performance (mean AUC – 0.791; after bootstrap correction – 0.776) and acceptable calibration. Pathogenic variants found in the LDLR/APO genes, glycated hemoglobin > 5.7%, and smoking or vaping made the greatest contribution to the risk. A practical algorithm for stratifying patients into 4 categories of risk, allowing for personalized approach to lipid-lowering therapy was suggested.

Conclusion. Despite the need for external validation and further prospective studies, IPAD-1.0 is the first comprehensive validated tool to assess a vascular risk in pediatric HeFH.

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