IMPACT-FH: Cascade Strategies Improve Testing for Familial Hypercholesterolemia

Laney Jones, PharmD, MPH
Credit: Washington University in St. Louis

Results of the IMPACT-FH study underline the potential of cascade testing strategies as an approach for improving the detection of familial hypercholesterolemia (FH).

A prospective, pragmatic study examining use of an innovative communication system to notify family members of a genetic FH result indicates this approach increases the likelihood of participating in cascade testing, with selection of at least 1 strategy associated with a 6-fold increase in likelihood while direct contact was associated with more than 16-fold increase in testing relative to a no-contact strategy.¹

“The innovative and optimized strategies implemented in the IMPACT-FH cascade testing program significantly improved FH cascade testing uptake compared to previous rates in a population genomic testing program and compared to families where no strategies were selected,” wrote investigators.¹ “We found direct contact was the most effective strategy for improving cascade testing uptake; it was also the least frequently chosen by probands.”

As a result of the elucidation of the cardiovascular risk associated with diagnosis as well as the advent of effective therapies for management, FH has found itself in the crosshairs of lipidologists and cardiologists in recent years. As with many genetic diseases, the need for greater testing and identification of those considered at high risk remains paramount for interventions aimed at improving prognosis.^1,2

The Identification Methods, Patient Activation, and Cascade Testing for FH (IMPACT-FH) study was a prospective pragmatic study examining use of implementation strategies to improve family communication and cascade testing for FH. Led by Laney Jones, PharmD, MPH, of the Geisinger Health, the study enrolled probands with an FH genetic result from the MyCode Community Health Initiative, with these probands able to choose whether or not they would share their FH results with adult blood relatives. If they chose to communicate, probands could select communication strategies that included use of a packet, a chatbot, and/or direct contact.¹

The primary outcome of interest for the study was the uptake of cascade testing, which was measured as the reported completion of genetic or cholesterol testing. Investigators pointed out generalized estimating equations models were used to identify factors associated with increased likelihood of testing.¹

In total 175 probands were identified for inclusion in the study. This cohort had a median age of 58.9 (Interquartile Range [IQR], 44.9 to 69.3), 58.9% were female, and 46.2% completed an appointment with a genetic counselor. Among this cohort, 70% chose at least 1 communication strategy for at least 1 adult relative. In total, probands shared information about 1915 adult and 163 minor relatives, with a mean of 1.2 strategies selected per adult relative.¹

Upon analysis, results indicated cascade testing was completed for 26.6% of adults with at least 1 strategy selected, 2.4% of adults without a strategy selected, and 25.2% of minor relatives. Further analysis revealed odds of undergoing cascade testing were greater among those with at least 1 strategy selected than those with (adjusted Odds Ratio [aOR], 6.32; 95% Confidence Interval [CI], 3.17 to 12.61) than those without a strategy selected. Investigators highlighted direct contact appeared to be the most effective strategy, with those experiencing direct contact having a 16.78-fold increased likelihood of undergoing cascade testing (aOR, 16.78; 95% CI, 8.53 to 15.51).¹

Investigators called attention to multiple limitations within their study to consider. These limitations included possibility of underestimated rates of cascade testing, a majority non-Hispanic White population, and use of an objective measure for estimating cascade testing.¹

In a related editorial, Jared A. Spitz, MD, Rebecca Miller, MS, and Jaideep Patel, MD, offered perspectives on the results of the study and the need for increased testing and early identification of genetic lipid disorders.²

“This study takes the field further in our understanding of the implementation of cascade screening for FH. It is imperative that future research continue focusing on the role of genetic counseling and integration of genetic counselors into multidisciplinary teams. Understanding barriers to sharing genetic information at a patient level needs to be understood so that solutions can be implemented to address them,” the trio wrote.² “Even so, there remains a staggeringly high rate of underdiagnosis of FH, and research into the lack of education and how to overcome this remains paramount.”

References:

1. ^{Jones LK, Campbell-Salome G, Walters NL, et al. Impact-FH study for implementing innovative family communication and cascade testing strategies for familial hypercholesterolemia. JACC: Advances. 2024;3(9):101198. doi:10.1016/j.jacadv.2024.101198}
2. ^{Spitz JA, Miller R, Patel J. The power of the pedigree. JACC: Advances. 2024;3(9):101201. doi:10.1016/j.jacadv.2024.101201}