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Record W3164994138 · doi:10.1002/clc.23627

Genetics, its role in preventing the pandemic of coronary artery disease

2021· review· en· W3164994138 on OpenAlex
Robert Roberts, Jacques Fair

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueClinical Cardiology · 2021
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchCanada Foundation for Innovation
KeywordsMedicineCoronary artery diseaseFamilial hypercholesterolemiaStatinClinical trialDiseaseInternal medicineFramingham Risk ScoreCholesterol

Abstract

fetched live from OpenAlex

Epidemiologists have claimed for decades that about 50% of predisposition for coronary artery disease (CAD) is genetic. Advances in technology made possible the discovery of hundreds of genetic risk variants predisposing to CAD. Multiple clinical trials have shown that cardiac events can be prevented by drugs to lower plasma low-density lipoprotein cholesterol (LDL-C). A major barrier to primary prevention is the lack of markers to identify those individuals at risk prior to the development of symptoms of the disease. Conventional risk factors are age-dependent, occurring mostly in the sixth or seventh decade, which is less than desirable for early primary prevention. A polygenic risk score, derived from the number of genetic risk variants predisposing to CAD inherited by an individual, has been evaluated in over 1 million individuals. The risk for CAD is stratified into high, intermediate, and low. Polygenic risk scores derived from retrospective genotyping of several clinical trials evaluating the effect of statin therapy or PCSK9 inhibitors show the genetic risk is reduced 40%-50% by decreasing plasma LDL-C. Prospective randomized placebo-controlled clinical trials document a 40%-50% reduction in cardiac events in individuals at high genetic risk associated with favorable lifestyle changes and increased physical activity. The polygenic risk score is not age-dependent and remains the same throughout life. Thus, the GRS is superior to conventional risk factors in identifying asymptomatic individuals at risk for CAD early in life for primary prevention. These results indicate clinical embracement of the GRS in primary prevention would be a paradigm shift in the treatment of the number one killer, CAD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.923
Threshold uncertainty score0.870

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.098
GPT teacher head0.412
Teacher spread0.314 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it