Underutilization of Guideline-Recommended Genetic Testing to Diagnose Familial Hypercholesterolemia in a Large, Real-world Cohort

Background/Synopsis Familial hypercholesterolemia (FH) is a common genetic condition that, if left untreated, is potentially fatal. Clinical practice guidelines recommend that genetic testing for FH be performed if low-density lipoprotein cholesterol (LDL-C) values are markedly elevated or with onset of premature coronary artery disease (CAD). Genetic testing can confirm diagnoses of clinical FH and promote cascade screening for family members. The actual adoption of genetic testing for diagnosis of FH has yet to be quantified using a large, real-world cohort. Objective/Purpose To quantify the frequency of genetic testing measures for patients who meet clinical indications for FH genetic screening in routine clinical practice settings. Methods Retrospective chart review using an automated EHR analysis engine was performed on the linked Veradigm EHR and claims data (35 million US patients) to identify patients who meet clinical guideline criteria for genetic testing for FH (Figure). Patients with a new diagnosis of primary hypercholesterolemia were identified using ICD-10 codes and free-text problem lists. Patients were required to have >1 year of both closed claims enrollment data and EHR data, including at least one LDL-C value. The cohort was further stratified by age and presence of a recorded family history of FH or premature CAD (Figure). Evidence of genetic testing within 6 months of hypercholesterolemia diagnosis and diagnosis of FH within 1 year of hypercholesterolemia diagnosis were captured for each patient using ICD codes, CPT codes, and text. Results 719 adults with no recorded family history of FH or premature CAD met clinical indications for genetic testing for FH. Of these patients, 26 (3.6%) were diagnosed with FH and 8 (1.1%) had evidence of genetic testing; only 2 patients had both a new diagnosis of FH and evidence of genetic testing. 250 pediatric patients with no recorded family history met clinical indications for evaluation; 28 (11%) were later diagnosed with FH and 5 (2.0%) received genetic testing. 11 pediatric patients with recorded family history met clinical indications for testing, and 5 (45%) were later diagnosed with FH. 1 of 16 (6.3%) adults with recorded family history were diagnosed with FH. Neither cohort with positive family history had evidence of genetic testing. Conclusions Genetic testing was found to be infrequently used in clinical practice, even in patients having a high index of suspicion of FH based on their LDL-C levels. Future work will determine how genetic testing may alleviate underdiagnosis/overdiagnosis of FH and influence disease management/outcomes. External Funding Yes Funding Sources Funding for the study was provided by Illumina, Inc. Familial hypercholesterolemia (FH) is a common genetic condition that, if left untreated, is potentially fatal. Clinical practice guidelines recommend that genetic testing for FH be performed if low-density lipoprotein cholesterol (LDL-C) values are markedly elevated or with onset of premature coronary artery disease (CAD). Genetic testing can confirm diagnoses of clinical FH and promote cascade screening for family members. The actual adoption of genetic testing for diagnosis of FH has yet to be quantified using a large, real-world cohort. To quantify the frequency of genetic testing measures for patients who meet clinical indications for FH genetic screening in routine clinical practice settings. Retrospective chart review using an automated EHR analysis engine was performed on the linked Veradigm EHR and claims data (35 million US patients) to identify patients who meet clinical guideline criteria for genetic testing for FH (Figure). Patients with a new diagnosis of primary hypercholesterolemia were identified using ICD-10 codes and free-text problem lists. Patients were required to have >1 year of both closed claims enrollment data and EHR data, including at least one LDL-C value. The cohort was further stratified by age and presence of a recorded family history of FH or premature CAD (Figure). Evidence of genetic testing within 6 months of hypercholesterolemia diagnosis and diagnosis of FH within 1 year of hypercholesterolemia diagnosis were captured for each patient using ICD codes, CPT codes, and text. 719 adults with no recorded family history of FH or premature CAD met clinical indications for genetic testing for FH. Of these patients, 26 (3.6%) were diagnosed with FH and 8 (1.1%) had evidence of genetic testing; only 2 patients had both a new diagnosis of FH and evidence of genetic testing. 250 pediatric patients with no recorded family history met clinical indications for evaluation; 28 (11%) were later diagnosed with FH and 5 (2.0%) received genetic testing. 11 pediatric patients with recorded family history met clinical indications for testing, and 5 (45%) were later diagnosed with FH. 1 of 16 (6.3%) adults with recorded family history were diagnosed with FH. Neither cohort with positive family history had evidence of genetic testing. Genetic testing was found to be infrequently used in clinical practice, even in patients having a high index of suspicion of FH based on their LDL-C levels. Future work will determine how genetic testing may alleviate underdiagnosis/overdiagnosis of FH and influence disease management/outcomes.