Evidence mapPaperPMID 41511773Full record

Trial reportJAMA network open2026

Opportunistic Genomic Screening for Familial Hypercholesterolemia to Improve Low-Density Lipoprotein Cholesterol: A Randomized Clinical Trial.

Jason L Vassy, Charles A Brunette, Thomas Yi, Themistocles L Assimes, Kurt D Christensen, Joshua W Knowles, Amy C Sturm, Yan V Sun, Nicholas Alexander, Mark P Cardellino and 11 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04178122 (Million Veteran Program Return of Actionable Results), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04178122 nacompletednot on this map

Million Veteran Program Return of Actionable Results

TypeinterventionalSponsorVA Office of Research and DevelopmentRan2020 to 2024Enrolled112ConditionsCardiovascular DiseaseArmsResult disclosure
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Jason L VassyVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Charles A BrunetteVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Thomas YiVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Themistocles L AssimesVA Palo Alto Healthcare System, Palo Alto, California.
Kurt D ChristensenHarvard Medical School, Boston, Massachusetts.
Joshua W KnowlesDivision of Cardiovascular Medicine, Cardiovascular Institute, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Amy C SturmOhio State Genomic Health, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Yan V SunAtlanta VA Healthcare System, Atlanta, Georgia.
Nicholas AlexanderBucharest University for Economic Studies, Bucharest, Romania.
Mark P CardellinoVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Alicia HarrisonVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Haley L GeretyVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Mary PyattVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Ron VeredVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Peter W F WilsonAtlanta VA Healthcare System, Atlanta, Georgia.
Pradeep NatarajanHarvard Medical School, Boston, Massachusetts.
Stacey B WhitbourneVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
J Michael GazianoVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Sumitra MuralidharVeterans Health Administration, Office of Research and Development, Washington, DC.
Morgan E DanowskiVeterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts.
Veterans Affairs Million Veteran Program

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Cholesterol, LDLGenetic TestingHyperlipoproteinemia Type IIAdultAgedFemaleHumansMaleMiddle AgedUnited StatesCholesterol, LDL

Identifiers

PMID41511773
PMCPMC12789956

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.