Abstract 42: Haptoglobin Genotype as a Marker of Vascular Intraplaque Hemorrhage
Bibliographic record
Abstract
Background: Intraplaque hemorrhage (IPH), a component of late stage atherosclerosis, is a critical factor in plaque destabilization leading to stroke and myocardial infarction. Magnetic resonance imaging (MRI) is able to identify IPH and allows for identification of high risk patients. Currently however, no routinely available tests are conducted to identify individuals at risk of IPH. IPH is a rich source of free hemoglobin (Hb), a potent oxidant. The plasma protein haptoglobin (Hp) binds Hb forming a Hb-Hp complex, that can be engulfed by tissue macrophages.The reduction in oxidative stress decreases vascular inflammation. In humans, the Hp gene has three different genotypes: Hp1-1, Hp2-2 and Hp1-2. The Hb-Hp2-2 complex has a lower binding affinity to macrophages, resulting in higher oxidative burden. Numerous studies have demonstrated a higher risk of cardiovascular events in Hp2-2 individuals. We therefore hypothesized that patients of a Hp2-2 genotype have a greater risk of MR-IPH. Methods: From 2010 to 2014, patients with non-surgical carotid artery disease (30-95% stenosis) underwent 3T carotid MRI that included a MR-IPH sequence. A radiologist with 25 years of expertise in MR-IPH imaging determined the presence of MR-IPH using widely accepted methods. Patients’ charts were blindly reviewed for demographics and medical history. Patients were genotyped for Hp1/2 using an established PCR genotyping method. Statistical association analysis was performed using logistic regression. Results and Conclusions: Out of the 80 recruited patients (mean age, 72.8 years; range 52-100), those with Hp2-2 genotype vs. Hp1-1/Hp1-2 had a prevalence of MR-IPH of 65% compared to 41%(p=0.09). Non-diabetics (HbA1c <6.5%) with Hp2-2 genotype had an increased risk of IPH compared to non-diabetics with Hp1-1/Hp 1-2 genotype (OR=3, 95% CI 1.04-8.73, p=0.03). Males were also at an increased risk of IPH (OR=4.05, 95% CI 1.53-10.70, p=0.004) and the majority (71%) of males with IPH were of the Hp2-2 genotype. In conclusion, non-diabetic Hp2-2 male patients with history of vascular disease are the population with the highest risk of developing IPH and they can be identified using simple haptoglobin genotype testing.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".