Familial Hypercholesterolemia Diagnosis and Management: Insights from the NIH Precision Medicine Initiative All of Us Study

Abstract

Background/Synopsis

Limited data exist regarding familial hypercholesterolemia (FH) diagnosis and treatment in diverse populations.

Objective/Purpose

We sought to assess patient characteristics and current treatment patterns among individuals with FH and/or elevated low-density lipoprotein cholesterol (LDL-C) in a diverse real-world cohort within the United States.

Methods

We examined data from the NIH Precision Medicine Initiative All of Us Research Program, a cross-sectional study beginning in 2015 inclusive of historically underrepresented groups. Among participants with >1 LDL-C measurement, we examined lipid-lowering medication utilization and treatment patterns among participants with and without FH diagnosis stratified by LDL-C. We additionally examined whether sex differences existed in treatment and diagnosis.

Results

Among 369,483 All of Us participants age ≥18 years, our study sample included 113,153 individuals who had at least one LDL-C measurement. Of these, 4018 (3.5%) had LDL-C ≥160 mg/dL, 733 (0.26%) had LDL-C ≥190 mg/dL, and 434 were diagnosed with FH (0.37%). Statin usage was found to be higher among men compared to women both in those with FH (84% vs. 70.3%, p=0.002) and without FH (54.2% vs. 39.2%, p<0.001) irrespective of LDL-C measures. Women tended to have higher mean LDL-C levels compared to men (130.9 mg/dL vs. 105.8 mg/dL, p<0.001 in those with FH and 106.9 mg/dL vs. 98.8 mg/dL p<0.001 in those without FH). Participants with FH were also more likely to be on statin therapy (75.2% vs 44.8%, p-value <0.001) with 18.4% on two or more types of lipid-lowering agents. Despite this, a higher percentage of FH participants had a history of >1 major ASCVD event (19.4% vs 10.7%, p-value <0.001), and exhibited higher mean LDL-C levels (121.9 mg/dL vs 103.9 mg/dL) compared to non-FH participants. Notably, only 30.5% of FH participants achieved the recommended LDL-C<100 mg/dL compared to 45.7% of those without FH (p-value<0.001). Furthermore, a majority (60.6%) of those already diagnosed with FH had LDL-C <130 mg/dL, including those not taking a lipid-lowering drug (Figure 1), questioning whether FH is being incorrectly diagnosed in some patients.

Conclusions

This study highlights the under and possible inappropriate diagnosis of FH and inadequate treatment of those diagnosed with FH among a real-world population.