Intervention at Circulating Homocysteine Levels >10 µmol/L for Primary Prevention of Cardiovascular Diseases: A Systematic Review and Dose–Response Meta‐Analysis
Bibliographic record
Abstract
OBJECTIVE: Several studies suggested that the risk of cardiovascular disease (CVD) had increased before individuals developed hyperhomocysteinemia. This study aimed to investigate the dose-response relationship between circulating homocysteine (Hcy) levels and the risk of CVD. METHODS: Observational studies examining the relationship between circulating Hcy levels and CVD risks were included. Searches were conducted on English databases (PubMed, Embase, and Web of Science) and Chinese databases (CNKI, WanFang, VIP, and SinoMed) in May 2025. Combined relative risks (RRs) or odds ratios (ORs) were calculated using random-effects models. The dose-response relationship between circulating Hcy levels and CVD risks was assessed using restricted cubic spline analysis. The risk of bias was assessed using the Newcastle-Ottawa Scale for cohort and case-control studies, and the Agency for Healthcare Research and Quality criteria for cross-sectional studies. Publication bias was assessed using funnel plots and the trim-and-fill method. RESULTS: A total of 117 original studies (35 cohort studies, 60 case-control studies, and 22 cross-sectional studies) were included, involving 504,469 participants with 43,089 CVD cases. Elevated circulating Hcy levels were significantly associated with increased CVD risks in all study types (RRs/ORs: 1.61-2.14). A non-linear dose-response relationship was observed between circulating Hcy levels and CVD risks (all p < 0.001), with thresholds at 10.4 µmol/L for cohort studies, and 10.0 µmol/L for both case-control studies and cross-sectional studies. CONCLUSIONS: In this meta-analysis, increased Hcy levels were linked to higher CVD risks. Circulating Hcy level >10 µmol/L may implement nutritional intervention in primary prevention of CVD.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Review About the Canadian research system: no · About a Canadian topic: no | Meta-analysis | high |
| gpt | no category Domain: not available · Genre: Review About the Canadian research system: no · About a Canadian topic: no | Meta-analysis | high |
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.016 | 0.012 |
| Bibliometrics | 0.002 | 0.002 |
| 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) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".