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Haptoglobin Phenotype and Cardiovascular Risk: The ACCORD Blood Pressure RCT

2025· article· en· W4416103124 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueHypertension · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHemoglobin structure and function
Canadian institutionsNova Scotia Health AuthorityDalhousie University
Fundersnot available
KeywordsHaptoglobinBlood pressureRandomized controlled trialPhenotypeHemoglobin

Abstract

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BACKGROUND: A relationship between hypertension and risk of incident cardiovascular disease, coronary artery disease, and stroke is widely reported in type 2 diabetes. However, trials testing intensive blood pressure control therapy versus standard therapy to reduce cardiovascular events have reported conflicting results, which could potentially be due to an unmeasured biological factor such as the common Hp (haptoglobin) phenotype. METHODS: Multivariable-adjusted Cox proportional hazards regression models assessed the relationship between intensive (versus standard) blood pressure control therapy and risk of composite cardiovascular disease, coronary artery disease, and stroke events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial in participants with the Hp2-2 phenotype (n=1527) separately from Hp1 allele carriers (n=2748). RESULTS: Intensive blood pressure therapy (versus standard therapy) was associated with a lower risk of composite cardiovascular disease among Hp1 allele carriers (hazard ratio, 0.76 [95% CI, 0.59–0.99]) but not among participants with the Hp2-2 phenotype (hazard ratio, 1.12 [95% CI, 0.80–1.55]; P -interaction=0.07). No significant hazard ratio was observed for intensive therapy versus standard therapy on risk of coronary artery disease (Hp1 allele carriers: hazard ratio, 0.85 [95% CI, 0.67–1.08]; Hp2-2 phenotype: hazard ratio, 1.12 [95% CI, 0.84–1.51]; P -interaction=0.11). Intensive therapy was associated with a lower risk of stroke among Hp1 allele carriers (hazard ratio, 0.53 [95% CI, 0.31–0.91]) but not among Hp2-2 participants (hazard ratio, 0.70 [95% CI, 0.33–1.46]; P -interaction=0.56). CONCLUSIONS: The lack of an effect of intensive blood pressure control on composite cardiovascular disease events in the original ACCORD blood pressure trial may be explained in part by variation in response among the Hp phenotypes. Further study and replication are required. REGISTRATION: URL: https://www.clinicaltrials.gov/study/NCT00000620?id=NCT00000620 ; Unique identifier: NCT00000620.

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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)0.000
metaresearch head score (Gemma)0.000
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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.836
Threshold uncertainty score0.318

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.005
GPT teacher head0.192
Teacher spread0.187 · 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