Understanding Implementation Challenges to Genetic Testing for Familial Hypercholesterolemia in the United States

Abstract

Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known pathogenic and likely pathogenic variations in FH-associated genes. Key organizations, such as the Centers for Disease Control and Prevention (CDC), American Heart Association (AHA), FH Foundation, and National Lipid Association (NLA), have recognized the clinical utility of FH genetic testing. However, FH genetic testing is underutilized in clinical practice in the US for reasons that are underexplored through the lens of implementation science. In this commentary, we discuss seven key implementation challenges that must be overcome to strengthen the clinical adoption of FH genetic testing in the US. These implementation challenges center on evidence of cost-effectiveness, navigating patient and provider preferences and concerns, gender and ethnic diversity and representation in genetic testing, and establishing clinical consensus around FH genetic testing based on the latest and most relevant research findings. Overcoming these implementation challenges is imperative to the mission of reducing CVD risk in the US.

A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

“…In fact, racial disparities in age of FH diagnosis have been reported among those registered within the International FH Foundation's CASCADE Registry [43]. One study showed that among 3537 adults diagnosed with FH across 26 sites in the US, Asians received FH diagnosis at youngest ages (37 years [29,44]) and Blacks received FH diagnosis at latest ages (54 years [37,45]; p < 0.0001), placing the Black population at a possibly higher risk of premature cardiovascular disease due to undiagnosed FH [43]. Therefore, we assessed race and/or ethnicity reported across all 21 studies.…”

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

“…Potential benefit may derive from the communication of genetic risk to patients, but the effectiveness of this may depend on the genetic literacy of the patient, as well as the practitioner. Education of patients, the public and health professionals about the role of genomics and genetic testing is therefore important and includes concerns relating to discriminatory underwriting of insurance based on genetic information …”

“…The ability of accurate risk prediction to alter therapy and improve outcomes beyond a small number of defined clinical scenarios remains uncertain and needs investigation. Further, key implementation challenges to be addressed include those already discussed, along with attention to gender and ethnic diversity in genetic testing; consensus among clinical guidelines informed by the latest clinical research; and establishing best practice for the communication of genetic results to patients and providers …”

“…Education of patients, the public and health professionals about the role of genomics and genetic testing is therefore important and includes concerns relating to discriminatory underwriting of insurance based on genetic information. 92,93 Access to genetic testing is in part determined by health insurers;…”

“…7 | CONTEMPORARY CHALLENGESKey knowledge gaps and avenues for future research in FH, as outlined by Hooper et al 7 are summarised inTable 2. Knowledge gaps and avenues for implementation and future research on genetic testing in FH7,92 Basic science and laboratory methods • Assessment of optimal cholesterol gene scores for clinical use • International harmonisation on variant interpretation: annotation and functionality • Identification of key modifier genes that alter penetrance of FH variants • Establishment and integration of international DNA repositoriesEpidemiology • Identification of new gene founder populations • Description of geographical variation in gene variants • Genetic epidemiology of FH in high-risk settings, for example, coronary care • Development and use of international genetic registries • Use of genetic information in data linkage studies…”