| Title: |
Opportunistic Genomic Screening for Familial Hypercholesterolemia to Improve Low-Density Lipoprotein Cholesterol ; A Randomized Clinical Trial |
| Authors: |
Vassy, Jason L.; Brunette, Charles A.; Yi, Thomas; Assimes, Themistocles L.; Christensen, Kurt D.; Knowles, Joshua W.; Sturm, Amy C.; Sun, Yan V.; Alexander, Nicholas; Cardellino, Mark P.; Harrison, Alicia; Gerety, Haley L.; Pyatt, Mary; Vered, Ron; Wilson, Peter W. F.; Natarajan, Pradeep; Whitbourne, Stacey B.; Gaziano, J. Michael; Muralidhar, Sumitra; Danowski, Morgan E.; Moser, Jennifer; Deen, Jennifer E.; Tsao, Philip S.; Hauser, Elizabeth; Kilbourne, Amy; Matheny, Michael; Oslin, Dave; Voora, Deepak; Brewer, Jessica V.; Brophy, Mary T.; Cho, Kelly; Churby, Lori; DuVall, Scott L.; Pyarajan, Saiju; Ringer, Robert; Selva, Luis E.; Shayan, Shahpoor (Alex); Stephens, Brady |
| Source: |
JAMA Network Open ; volume 9, issue 1, page e2549664 ; ISSN 2574-3805 |
| Publisher Information: |
American Medical Association (AMA) |
| Publication Year: |
2026 |
| Description: |
Importance The clinical benefit of opportunistic genomic screening for familial hypercholesterolemia (FH) has not been demonstrated in a randomized clinical trial (RCT). Objective To evaluate the impact of returning clinically confirmed FH-associated genetic results on low-density lipoprotein cholesterol (LDL-C) levels. Design, Setting, and Participants This RCT was performed within the Veterans Health Administration, a large national health care system, and linked to the Million Veteran Program (MVP), a research biobank. Participants were MVP enrollees suspected to have an FH-associated genetic variant, as identified in their research data. Recruitment occurred from February 27, 2020, to September 20, 2022, and 6-month follow-up was completed October 21, 2024. Interventions Delivery of clinical genetic confirmation testing and telegenetic counseling at baseline (immediate results arm) vs after 6 months (delayed results arm). Main Outcomes and Measures Change in LDL-C levels (primary outcome) and proportions with treatment intensification and achievement of LDL-C target levels at 6 months (secondary outcomes). Results The trial randomized 112 participants across 28 US states (mean age, 65.9 [range, 36-91] years; 94 [83.9%] men). Baseline mean (SD) LDL-C level was 109.5 (55.5) mg/dL, and 86 participants (76.8%) were already receiving therapy to lower lipid levels. At 6 months, the between-arm difference in LDL-C level reduction was −10.5 (95% CI, −21.9 to 1.0) mg/dL ( P = .07; Cohen d = 0.34). Bayesian analysis suggested a high probability of benefit but was exploratory. Treatment was intensified in 11 of 55 participants (20.0%) in the immediate results arm vs 5 of 57 (8.8%) in the delayed results arm ( P = .09). Fifteen participants (27.3%) in the immediate results arm vs 14 (24.6%) in the delayed results arm ( P = .74) achieved LDL-C target levels. Thirty of 49 participants (61.2%) in the immediate results arm who completed this information shared their genetic result with a total of 98 relatives. Conclusions ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1001/jamanetworkopen.2025.49664 |
| Availability: |
https://doi.org/10.1001/jamanetworkopen.2025.49664; https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2843522/vassy_2026_oi_251331_1767023544.57962.pdf |
| Accession Number: |
edsbas.C32301F8 |
| Database: |
BASE |