JAMA network open · 2026
Opportunistic Genomic Screening for Familial Hypercholesterolemia to Improve Low-Density Lipoprotein Cholesterol: A Randomized Clinical Trial.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Veterans Affairs Million Veteran Program
Аннотация
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 AND RELEVANCE: In this RCT, opportunistic genomic screening for FH plus telegenetic counseling did not result in a statistically significant improvement in LDL-C levels and clinical management; however, the findings suggest that there may be a small to moderate benefit favoring the immediate results arm. Further research should be conducted to confirm these findings, optimize implementation strategies, and assess the long-term effects on cardiovascular outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04178122.
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 AND RELEVANCE: In this RCT, opportunistic genomic screening for FH plus telegenetic counseling did not result in a statistically significant improvement in LDL-C levels and clinical management; however, the findings suggest that there may be a small to moderate benefit favoring the immediate results arm. Further research should be conducted to confirm these findings, optimize implementation strategies, and assess the long-term effects on cardiovascular outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04178122.