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O042 - FGF-5 UNIQUELY IDENTIFIES SUBJECTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM A PROTEOMICS STUDY (ID 1231)
Abstract
Background and Aims
Targeted proteomics can identify subjects at high Atherosclerotic Cardiovascular Diseases (ACVD) risk in the general populations beyond the known risk factors. Familial Hypercholesterolemia (FH), is a genetically determined disease that exposes to a lifelong high burden of LDL cholesterol (LDL-C) resulting in premature cardiovascular disease. We aimed to address the question whether targeted proteomics could differentiate subjects with FH from the general population even with similar levels of LDL-C.
Methods
We compared the plasma relative abundance of 264 proteins (Proximity Extension Assay) in 133 heterozygous FH, in 586 normocholesterolemic subjects (“controls”) from the “PLIC” study cohort and in 55 subjects with high LDL cholesterol, but not diagnosed as FH, from the same population (LDL-C 190-220 mg/dL not on statins). A Machine Learning (ML) boosting prediction model identified the protein markers representative of FH (Random Forest classifiers).
Results
FGF-5 resulted as the most powerful plasma protein in differentiating FH subjects from the controls, with an excellent performance (Area Under the Curve (AUC)=0.995 (0.985-1.000); sensitivity=100%; specificity=99.54%; P<0.0001). Of note, FGF-5 also emerged as the top, unique, protein in differentiating FH subjects from subject with elevated LDL-C (AUC= 1.000 (0.914-1.000; sensitivity=100%, specificity=100% and P<0.001) also when matched with FH for plasma LDL-C levels.
Conclusions
Specific plasma proteomics markers allow a clear-cut identification of FH patients as compared to controls and the finding that FH proven subjects with relatively low LDL-C can be easily distinguished from non-FH with the same LDL-C strongly suggests that the LDL-C burden might be responsible for our findings.