Dose-Response Association Between Bilirubin and Cardiovascular Disease: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
The association between bilirubin (BIL) and cardiovascular disease (CVD) remains controversial. We performed a meta-analysis of prospective studies to evaluate this association in the general population. We searched PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases through to September 2021. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality. The pooled effect estimate was calculated by the fixed-effect model or random-effect model. We included 12 prospective studies (368 567 participants). The pooled risk ratio of CVD for the lowest vs highest groups of BIL levels was .75 (95% CI: .58-.97) with high heterogeneity (I<sup>2</sup> = 87.5%, <i>P</i> < .001). Similar associations were observed for coronary heart disease and stroke. We further performed a “dose-response” meta-analysis, and a significant U-shaped relationship between circulating (most values were serum bilirubin, but a few were plasma bilirubin) BIL and CVD (<i>P</i> < .01) was observed. The lowest risk of CVD events was observed in participants with a BIL of 17-20 µmol/L in serum and/or plasma. In conclusion, there was a U-shaped dose-response relationship between BIL and CVD, especially for men. Further studies are needed to confirm our findings and identify the mechanisms involved as well as any prognostic or therapeutic potential.
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How this classification was reachedexpand
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 | 0.011 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.069 | 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 teacher head, 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".