Optimizing communication strategies and designing a comprehensive program to facilitate cascade testing for familial hypercholesterolemia.

BACKGROUND: This project aimed to optimize communication strategies to support family communication about familial hypercholesterolemia (FH) and improve cascade testing uptake among at-risk relatives. Individuals and families with FH provided feedback on multiple strategies including: a family letter, digital tools, and direct contact. METHODS: Feedback from participants was collected via dyadic interviews (n = 11) and surveys (n = 98) on communication strategies and their proposed implementation to improve cascade testing uptake. We conducted a thematic analysis to identify how to optimize each strategy. We categorized optimizations and their implementation within the project's healthcare system using a Traffic Light approach. RESULTS: Thematic analysis resulted in four distinct suggested optimizations for each communication strategy and seven suggested optimizations that were suitable across all strategies. Four suggestions for developing a comprehensive cascade testing program, which would offer all optimized communication strategies also emerged. All optimized suggestions coded green (n = 21) were incorporated. Suggestions coded yellow (n = 12) were partially incorporated. Only two suggestions were coded red and could not be incorporated. CONCLUSIONS: This project demonstrates how to collect and analyze stakeholder feedback for program design. We identified feasible suggested optimizations, resulting in communication strategies that are patient-informed and patient-centered. Optimized strategies were implemented in a comprehensive cascade testing program.

Lipoprotein(a): An important piece of the ASCVD risk factor puzzle across diverse populations.

Elevated lipoprotein(a) (Lp[a]) is an independent, genetic risk factor for atherosclerotic cardiovascular disease (ASCVD) that impacts ~1.4 billion people globally. Generally, Lp(a) levels remain stable over time; thus, most individuals need only undergo Lp(a) testing through a non-fasting blood draw once in their lifetime, unless elevated Lp(a) is identified. Despite the convenience of the test for clinicians and patients, routine Lp(a) testing has not been widely adopted. This review provides a guide to the benefits of Lp(a) testing and solutions for overcoming common barriers in practice, including access to testing and lack of awareness. Lp(a) testing provides the opportunity to reclassify ASCVD risk and drive intensive cardiovascular risk factor management in individuals with elevated Lp(a), and to identify patients potentially less likely to respond to statins. Moreover, cascade screening can help to identify elevated Lp(a) in relatives of individuals with a personal or family history of premature ASCVD. Overall, given the profound impact of elevated Lp(a) on cardiovascular risk, Lp(a) testing should be an essential component of risk assessment by primary and specialty care providers.

Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial.

BACKGROUND: Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science-including mixed-methods contextual inquiry with clinicians, patients, and health system constituents-to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach. METHODS: We will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity. DISCUSSION: We will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05750667. Registered 15 February 2023-retrospectively registered, https://clinicaltrials.gov/study/NCT05750667 .

It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Innovative Implementation Strategies for Familial Hypercholesterolemia Cascade Testing: The Impact of Genetic Counseling.

The IMPACT-FH study implemented strategies (packet, chatbot, direct contact) to promote family member cascade testing for familial hypercholesterolemia (FH). We evaluated the impact of genetic counseling (GC) on medical outcomes, strategy selection, and cascade testing. Probands (i.e., patients with FH) were recommended to complete GC and select sharing strategies. Comparisons were performed for both medical outcomes and strategy selection between probands with or without GC. GEE models for Poisson regression were used to examine the relationship between proband GC completion and first-degree relative (FDR) cascade testing. Overall, 46.3% (81/175) of probands completed GC. Probands with GC had a median LDL-C reduction of -13.0 mg/dL (-61.0, 4.0) versus -1.0 mg/dL (-16.0, 17.0) in probands without GC (p = 0.0054). Probands with and without GC selected sharing strategies for 65.3% and 40.3% of FDRs, respectively (p < 0.0001). Similarly, 27.1% of FDRs of probands with GC completed cascade testing, while 12.0% of FDRs of probands without GC completed testing (p = 0.0043). Direct contact was selected for 47 relatives in total and completed for 39, leading to the detection of 18 relatives with FH. Proband GC was associated with improved medical outcomes and increased FDR cascade testing. Direct contact effectively identified FH cases for the subset who participated.

Utilizing innovative implementation strategies for familial hypercholesterolemia: Implementation outcomes from the IMPACT-FH study.

BACKGROUND: Cascade testing can be highly effective in identifying individuals with familial hypercholesterolemia (FH) and help prevent atherosclerotic cardiovascular disease. The IMPACT-FH cascade testing program offered multiple optimized implementation strategies to improve FH cascade testing uptake. OBJECTIVE: Guided by the Conceptual Model of Implementation Research, this study assessed the IMPACT-FH cascade testing program's implementation outcomes. METHODS: Implementation outcomes were assessed qualitatively and quantitatively. Interviews were conducted with 33 IMPACT-FH program participants including 15 probands, 12 relatives, and 6 healthcare professionals (HCPs). Transcripts were analyzed using thematic analysis to investigate implementation outcomes. Descriptive statistics were analyzed for scaled implementation outcome measures asked after interviews. RESULTS: Participants described adopting strategies offered in the IMPACT-FH program because they presented an opportunity to pursue low-cost FH cascade testing. Participants identified barriers to feasibility including: the complexity of disclosing an FH result and offering strategies on, inherent limitations of probands choosing strategies, confusion over testing costs, limitations sharing with relatives' clinicians, discomfort with chatbot technology, and concerns about the workload for HCPs. Participants evaluated the program positively regarding its appropriateness (Mean (M) = 4.70, Standard Deviation (SD) = 0.41), acceptability (M = 4.79, SD = 0.40), and feasibility (M = 4.24, SD = 0.53). CONCLUSION: The IMPACT-FH cascade testing program and its strategies were evaluated as valuable to adopt and highly appropriate, acceptable, and feasible by participants. Participants identified areas to enhance the program that could improve FH cascade testing uptake.