Abstract 13391: The Natural History of Familial Hypercholesterolemia Diagnosis, Treatment, and Outcomes in Patients With Incidental LDLR Pathogenic Mutation Found in Population Based Sequencing Study

Introduction: The HerediGene Population Study is a collaborative between Intermountain Health and deCODE genetics that seeks to understand the genetics behind diseases to better predict and prevent disease. Here we describe the natural history of familial hypercholesterolemia (FH) diagnosis (dx), treatment, and outcomes in HerediGene patients (pts) with an LDLR gene variant.

Methods: From the first 32,159 sequenced pts, 157 (0.05%) had a pathogenic/likely pathogenic variant in LDLR. These LDLR carriers were divided into three groups - pts with no prior FH dx (n=47; 30%), pts with an FH dx made after a major adverse cardiovascular event (including, myocardial infarction, heart failure hospitalization, stroke, peripheral artery disease, and carotid artery disease) (n=41; 26%), and pts with an FH dx made prior to any MACE (n=69, 44%) (this is the referent group). The natural history of FH was examined using pairwise comparisons between the referent group and each of the first two groups.

Results: The clinical characteristics, LDL-C values, treatments, and outcomes are shown in the Table. The age at last visit or death was similar for all these groups (median=62). Compared to pts without an FH dx, pts with FH dx prior to a MACE had significantly more LDL-C measurements, increased statin and other lipid-lowering medications, and had a large change in LDL-C measurements. They were slightly, but not statistically, less likely to have subsequent MACE (25% vs 28%; p=0.72). The LDL-C measurements and statin use were similar for those pts with FH dx after MACE and pts with FH dx prior to MACE. However, pts with FH dx after a MACE had higher rates of death (36.6% vs 11.6%; p=0.002).

Conclusions: Aggressive treatment for and subsequent decrease in LDL-C following FH dx in pts with LDLR mutation, highlight the need for early diagnosis. Furthermore, if this dx was made prior to MACE the death rate was lower. Larger sized studies are needed, but these findings provide support for early screening for FH.