What is the clinical question being addressed?
What is the prevalence and trend in FH diagnostic code (E78.01) use in the United States since 2016?
What is the main finding?
FH diagnostic code use increased substantially; however, fewer than half of expected cases were captured during 2016-2024, suggesting most affected individuals remain undiagnosed or have yet to be assigned a specific FH diagnostic code.
Familial hypercholesterolemia (FH) is a genetic disorder marked by significantly elevated low-density lipoprotein cholesterol from birth and increased risk of premature cardiovascular disease if untreated.1,2 Until October 2016, there was no specific International Classification of Diseases (ICD) code for FH in the United States, limiting its identification within health care databases and contributing to underdiagnosis.3 The introduction of ICD-10 code E78.01 has enabled better systematic identification and tracking of FH, but data on its real-world use remain unclear. Understanding the adoption of this code is valuable, as accurate coding can support timely diagnosis, appropriate therapy, and population-level surveillance. We evaluated the utilization of E78.01 in a large U.S. health care database and characterized associated demographics and lipid-lowering therapy (LLT) use.
Methods
The data set for this study was obtained from Epic Cosmos, a large-scale nationwide electronic health record database comprising a representative sample of patients receiving care across the United States.4 Epic Cosmos integrates both outpatient and inpatient health records into a single, comprehensive system for research that does not require an internal review board approval. The platform contains deidentified information from the longitudinal health care records of approximately 300 million patients and over 17 billion health care encounters from participating health systems across the United States.
Among 300,232,949 individuals with data between October 1, 2016, and December 31, 2024, patients with a final billing code E78.01 were queried. Overall prevalence and annual trends were evaluated using the Mann-Kendall test in the entire patient population and within 3 subpopulations: patients with any diagnosis, patients with recorded encounters only, and patients with billed diagnoses only. Annual prevalence estimates used in examining temporal trends were calculated using data specific to each calendar year, with numerators defined as patients having at least one final billing code E78.01 during that year and denominators including patients contributing data within that same calendar year. Demographics and LLT use were compared between patients with and without the FH code.
Results
The number of patients diagnosed with FH using E78.01 increased substantially since 2016 (Figure 1). Overall, 509,961 patients (1.7 per 1,000 persons) received code E78.01, representing only 42% of the expected FH cases (n = 1,200,932) based on an assumed prevalence of 1 per 250 individuals. Among subspecialties, the largest proportions of patients with E78.01 were seen in primary care (n = 263,467; 51.7%), cardiology (n = 113,805; 22.3%), and endocrinology (n = 9,051; 1.8%), with the remaining patients distributed across other departments.
Figure 1.
Annual Prevalence of FH Diagnostic Code (E78.01) Use
Mann-Kendall Trend P value for all but the study population with billed diagnosis only was <0.05. Restricting the study populations to patients with encounters or any diagnoses or billed diagnoses only yielded higher prevalence estimates. FH = familial hypercholesterolemia.
Restricting analyses to subpopulations with encounters or diagnoses only yielded higher prevalence estimates (Figure 1). Patients with E78.01 were more likely to be aged 18 to 65 years (56.5% vs 51.8%) or >65 years (44.9% vs 17.0%), female (55.2% vs 52.3%), and White (82.4% vs 62.6%) compared with those without the code. Among patients with E78.01, 406,958 (79.8%) received at least one LLT. Including those treated with a combination of therapies, overall statin use in this population was 77%, ezetimibe 17%, and proprotein convertase subtilisin/kexin type 9 inhibitors 11%.
Discussion
In this large, nationally representative electronic health record database, we found that use of the ICD-10 code for FH (E78.01) has increased substantially since its introduction in 2016. However, fewer than half of the expected FH cases were likely captured across U.S. health care systems during 2016-2024, suggesting that most individuals with FH remain undiagnosed or have yet to be assigned a specific FH diagnostic code. Interestingly, when examining subspecialty distribution, the largest proportion of patients assigned E78.01 were seen in primary care. This may reflect the central role of primary care in identifying patients through routine lipid screening and longitudinal patient relationships, as well as referral patterns to specialists once an FH diagnosis is suspected. These findings underscore the need to further expand code adoption, which may improve FH identification, follow-up, LLT use, and outcomes in this high-risk population. New diagnostic codes for heterozygous FH, homozygous FH, and unspecified FH, approved on October 1, 2025, may further enhance diagnostic precision and surveillance.5
This study has some limitations, including its retrospective design and incomplete or absent data on key variables such as low-density lipoprotein cholesterol levels, genetic test results, and other measures commonly used in FH diagnostic criteria, such as the Dutch Lipid Clinic Network score and Simon Broome. These gaps make it difficult to fully determine whether the observed findings reflect underdiagnosis, underuse of the code, or both. Further investigation is needed to establish the predictive value of E78.01 and to evaluate strategies for improving consistent and equitable application of this code in clinical practice.
Funding Support and Author Disclosures
This study was partly funded by HL154996 from U.S. National Institutes of Health. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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