**Background:** Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder with a prevalence of 1 in 250 that leads to premature cardiovascular disease when left untreated. Patients with a pathogenic variant in an FH gene have triple the risk for atherosclerotic cardiovascular disease (ASCVD) at any LDL-C level due to lifelong exposure. Diagnosis often occurs in middle-aged adults after premature ASCVD, yet event rates for FH patients with prevalent ASCVD are 5-fold higher compared to those with no prior ASCVD. Treatment beginning in adolescence lowers ASCVD risk before age 40 from about 25% to less than 1%. Despite existing diagnostic criteria and treatment guidelines, FH remains underdiagnosed and undertreated, with preliminary data from the MyCode program at Geisinger showing cascade testing had occurred for only approximately 3.5% of at-risk relatives. This paper describes a systematic adapted intervention and implementation mapping approach to identify and match implementation strategies to barriers across all three components of FH care: identification, cascade testing, and management.
**Methods:** Data were collected using two methods: (1) a scoping review of PubMed from inception to December 1, 2021, using keywords including 'barriers' or 'facilitators' and 'familial hypercholesterolemia', which yielded 86 potential articles with 25 included in the final analysis after applying exclusion criteria; and (2) a parallel mixed-methods study recruiting individuals and families with FH from Geisinger and the Family Heart Foundation to participate in either dyadic interviews (11 dyads/22 individuals) or online surveys (98 respondents). Data were used in a modified 6-step intervention mapping process: Step 1 (needs assessment) identified barriers and facilitators from the literature and participant data; Step 2 (program outcomes) defined behavioral changes needed at individual, clinician, and health system levels and ranked determinants by changeability and importance via a survey sent to the study team; Step 3 (theory and evidence-based strategies) mapped results to the Expert Recommendations for Implementing Change (ERIC) compilation; and Steps 4–6 (program development, implementation, and evaluation) were demonstrated using the CARE-FH study as an example.
**Key Results:** The scoping review included 25 studies published between 2002 and 2021: 12 referenced identification, 8 referenced cascade testing, and 16 referenced management, with only two studies addressing all three components. In the mixed-methods study, 120 total participants (90 female, 30 male; 109 diagnosed with FH, 6 at-risk, 5 not at-risk spouses/caregivers) completed interviews or surveys. Barriers were categorized at three levels: individual (lack of awareness, cost, insurance coverage, non-adherence, side effects, stigma and health anxiety, familial communication dynamics, privacy concerns, competing demands), clinician (lack of awareness, belief there is a lack of evidence, competing clinical demands, inadequate record keeping, poor reimbursement, lack of comfort with genetic disorders), and health system (gaps in access to care, lack of genetic testing infrastructure, lack of formal screening programs). The most important and changeable determinants across all levels were knowledge, attitude, and risk perception. Implementation strategies mapped to the ERIC compilation included: altering financial incentives, changing record systems, conducting dynamic educational meetings, creating new clinical teams, developing and distributing educational materials, identifying champions, involving patients and family members, reminding clinicians, and using mass media.
**Clinical Implications:** This study provides a replicable, systematic framework for developing evidence-based implementation strategies to improve FH care across all three components. The CARE-FH study, funded by NHLBI, is operationalizing strategies from this mapping process to improve FH identification in primary care at Geisinger, using a 1-year pre-implementation phase with surveys, contextual inquiries, and pilot testing. The evaluation plan includes implementation outcomes (adoption, penetration, acceptability, feasibility, fidelity, sustainability, and cost) and service/health outcomes (timeliness, safety, LDL-C reduction, return of genetic results, and initiation of cascade testing). By addressing barriers at multiple levels simultaneously, this approach goes beyond prior work that focused on only one component or level of FH care, and the standardized reporting method using the ERIC compilation enables replication and adaptation by other health systems.