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Record W4382929792 · doi:10.1016/j.phrs.2023.106843

Daring to dream: Targeting lipoprotein(a) as a causal and risk-enhancing factor

2023· review· en· W4382929792 on OpenAlexafffund
Marlys L. Koschinsky, Erik S.G. Stroes, Florian Kronenberg

Bibliographic record

VenuePharmacological Research · 2023
Typereview
Languageen
FieldMedicine
TopicLipoproteins and Cardiovascular Health
Canadian institutionsWestern University
FundersCanadian Institutes of Health ResearchOesterreichische NationalbankHeart and Stroke Foundation of Canada
KeywordsLipoprotein(a)MedicineMendelian randomizationLipoproteinInternal medicineRisk factorPopulationDiseaseAtherosclerotic cardiovascular diseaseCardiologyEndocrinologyCholesterolGeneGeneticsBiologyGenotypeGenetic variants

Abstract

fetched live from OpenAlex

Lipoprotein(a) [Lp(a)], a distinct lipoprotein class, has become a major focus for cardiovascular research. This review is written in light of the recent guideline and consensus statements on Lp(a) and focuses on 1) the causal association between Lp(a) and cardiovascular outcomes, 2) the potential mechanisms by which elevated Lp(a) contributes to cardiovascular diseases, 3) the metabolic insights on the production and clearance of Lp(a) and 4) the current and future therapeutic approaches to lower Lp(a) concentrations. The concentrations of Lp(a) are under strict genetic control. There exists a continuous relationship between the Lp(a) concentrations and risk for various endpoints of atherosclerotic cardiovascular disease (ASCVD). One in five people in the Caucasian population is considered to have increased Lp(a) concentrations; the prevalence of elevated Lp(a) is even higher in black populations. This makes Lp(a) a cardiovascular risk factor of major public health relevance. Besides the association between Lp(a) and myocardial infarction, the relationship with aortic valve stenosis has become a major focus of research during the last decade. Genetic studies provided strong support for a causal association between Lp(a) and cardiovascular outcomes: carriers of genetic variants associated with lifelong increased Lp(a) concentration are significantly more frequent in patients with ASCVD. This has triggered the development of drugs that can specifically lower Lp(a) concentrations: mRNA-targeting therapies such as anti-sense oligonucleotide (ASO) therapies and short interfering RNA (siRNA) therapies have opened new avenues to lower Lp(a) concentrations more than 95%. Ongoing Phase II and III clinical trials of these compounds are discussed in this review.

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.

How this classification was reachedexpand

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)0.009
metaresearch head score (Gemma)0.007
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.987
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0090.007
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0010.002

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 head0.289
GPT teacher head0.530
Teacher spread0.241 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations21
Published2023
Admission routes2
Has abstractyes

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