Association of Hepatocyte Growth Factor and Angiopoietin-2 with Systemic Cardiovascular Risk in Patients with Peripheral Artery Disease
Bibliographic record
Abstract
Background/Objectives: Major adverse cardiovascular events (MACE) are the primary cause of mortality among individuals with peripheral artery disease (PAD). Despite this, there is limited research on biomarkers that can predict MACE risk in this population. Proteins involved in angiogenesis are integral to both systemic circulation and the development of atherosclerosis, indicating their potential as prognostic markers. This study aimed to identify angiogenesis-related proteins associated with MACE risk in PAD patients. Methods: We conducted a prospective cohort study involving 250 patients diagnosed with PAD. At baseline, plasma levels of 17 angiogenesis-related proteins were measured. Participants were followed for two years, with the primary outcome being the incidence of MACE—a composite of stroke, myocardial infarction, or death. Protein concentrations were compared between those who experienced 2-year MACE and those who did not using the Mann–Whitney U test. Proteins showing significant differences were further analyzed using Cox proportional hazards modeling to assess their independent associations with MACE, adjusting for baseline demographic and clinical variables, including prior coronary and cerebrovascular disease. Kaplan–Meier survival analysis was also employed to compare MACE-free survival based on protein concentration levels. Results: The average age of participants was 69 years (SD 9), with 32% (n = 80) being female. Over the two-year follow-up, 48 patients (19.8%) experienced MACE. Among the proteins assessed, only hepatocyte growth factor (HGF) and angiopoietin-2 were significantly elevated in patients who developed MACE (HGF: 390.83 [SD 319.16] vs. 300.55 [SD 177.53] pg/mL, p < 0.001; angiopoietin-2: 23.67 [SD 17.60] vs. 19.36 [SD 12.06] pg/mL, p = 0.020). Multivariable Cox analysis confirmed that elevated levels of both HGF (adjusted HR 1.37; 95% CI 1.14–1.64; p = 0.001) and angiopoietin-2 (adjusted HR 1.27; 95% CI 1.04–1.55; p = 0.016) were independently associated with increased 2-year MACE risk. Kaplan–Meier curves demonstrated significantly reduced MACE-free survival in patients with higher levels of HGF and angiopoietin-2. Conclusions: HGF and angiopoietin-2 emerged as significant, independent predictors of 2-year MACE in patients with PAD. Measuring plasma levels of these proteins may enhance risk stratification, guiding referrals to appropriate cardiovascular specialists and informing the intensity of medical management. This biomarker-based precision medicine approach holds potential for improving cardiovascular outcomes in the PAD population.
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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 | 0.001 | 0.002 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".