Haptoglobin Phenotype and Cardiovascular Risk: The ACCORD Blood Pressure RCT
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".