Katherine A. Wilemon

Background Individuals with familial hypercholesterolemia (FH) require intensive lipid-lowering therapy, starting with high-intensity statins and adding ezetimibe and PCSK9 inhibitors (PCSK9i) as needed to reach target LDL-C levels. There are limited data on disparities in the use of these therapies among individuals with FH in the US. Methods We queried a large US healthcare claims repository consisting of 324 million individuals, focusing on prescriptions for high-intensity statins, ezetimibe, and PCSK9i in two patient groups: those diagnosed with FH (ICD-10 E.78.01) and those not diagnosed with FH but identified as having probable FH (PFH) via the FIND-FH® machine learning algorithm. We used multivariable regression models to examine correlations with demographic/socioeconomic variables. Results In the FH cohort (n = 85,457), 45.9% were female, 79.4% identified as White, 12.2% Black, and 8.4% as Hispanic. In the PFH cohort (n = 287,580), 42.2% were female, 78.2% White, 13.7% as Black, and 8.1% as Hispanic. Males were more likely to be prescribed high-intensity statins than females: odds ratio (OR) [95% confidence interval (CI)] = 2.05 [1.97, 2.13] and 1.60 [1.56,1.63] in the FH and the PFH cohorts, respectively. In both cohorts, White individuals were more likely to get ezetimibe, PCSK9i, or combination therapy compared to Black individuals (ORs: 1.12-1.40). Higher income was associated with increased odds of receiving these treatments (OR: 1.17-1.59 for incomes >$50,000). Higher education was linked to a higher likelihood of combination therapy (ORs [95% CI] = 1.49 [1.33, 1.68] and 1.18 [1.10, 1.27] in the FH and PFH cohorts, respectively). Conclusions Real-world data indicate that more aggressive lipid-lowering therapy (ezetimibe and PCSK9i) is more often prescribed to White individuals, individuals with higher income, or those with advanced education, highlighting the need to improve equity in cardiovascular risk reduction for all individuals with FH. What is new? Health disparities exist for individuals with FH, regardless of whether they’ve been diagnosed. The use of ezetimibe and PCSK9i is more likely to occur in individuals who are White, higher income, and advanced education. What are the clinical Implications Addressing health disparities in FH requires a multifaceted approach, including systemic changes to reduce bias in healthcare systems. Ensuring equitable access to expensive lipid medications, such as PCSK9 inhibitors, is crucial for individuals from lower socioeconomic groups. Providing access to case managers and geneticists can enhance health education and support, ultimately improving treatment outcomes for individuals with FH.

To the Editor The preamble to the USPSTF Recommendation Statement on screening for lipid disorders in children and adolescents states that the USPSTF is committed to mitigating the health inequities that prevent people from fully benefiting from preventive services.¹ However, the conclusion of that Recommendation Statement that there is insufficient evidence to recommend screening for lipid disorders in children and adolescents may contribute to inequities in the prevention of heart disease later in life.

Background: Data mining of electronic health records to identify patients suspected of familial hypercholesterolemia (FH) has been limited by absence of both phenotypic and genomic data in the same cohort. Methods and Results: Using the Geisinger MyCode Community Health Initiative cohort (n=130 257), we ran 2 screening algorithms (Mayo Clinic [Mayo] and flag, identify, network, deliver [FIND] FH) to determine FH genetic and phenotypic diagnostic yields. With 29 243 excluded by Mayo (for secondary causes of hypercholesterolemia, no lipid value in electronic health records), 52 034 excluded by FIND FH (insufficient data to run the model), and 187 excluded for prior FH diagnosis, a final cohort of 59 729 participants was created. Genetic diagnosis was based on presence of a pathogenic or likely pathogenic variant in FH genes. Charts from 180 variant‐negative participants (60 controls, 120 identified by FIND FH and Mayo) were reviewed to calculate Dutch Lipid Clinic Network scores; a score ≥5 defined probable phenotypic FH. Mayo flagged 10 415 subjects; 194 (1.9%) had a pathogenic or likely pathogenic FH variant. FIND FH flagged 573; 34 (5.9%) had a pathogenic or likely pathogenic variant, giving a net yield from both of 197 out of 280 (70%). Confirmation of a phenotypic diagnosis was constrained by lack of electronic health record data on physical findings or family history. Phenotypic FH by chart review was present by Mayo and/or FIND FH in 13 out of 120 versus 2 out of 60 not flagged by either ( P <0.09). Conclusions: Applying 2 recognized FH screening algorithms to the Geisinger MyCode Community Health Initiative identified 70% of those with a pathogenic or likely pathogenic FH variant. Phenotypic diagnosis was rarely achievable due to missing data.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real‐world” setting. Untreated low‐density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P =0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow‐up, despite multiple lipid‐lowering treatment, low‐density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid‐lowering treatments were prescribed for 18%; 40% were on no lipid‐lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid‐lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.