| Title: | Allostatic load-cardiovascular disease associations and the mediating effect of inflammatory factors: a prospective cohort study |
| Journal: | Frontiers in Cardiovascular Medicine |
| Published: | 5 Jan 2026 |
| DOI: | https://doi.org/10.3389/fcvm.2025.1724572 |
Publication 16877
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Abstract
Allostatic load (AL) captures multisystem dysregulation that accrues with chronic stress and may shape cardiovascular disease (CVD) risk through neuroendocrine and immune pathways. Robust population-scale evidence clarifying the exposure-response pattern and the extent of inflammatory mediation remains limited. In the UK Biobank, we analyzed 205,504 adults free of CVD at baseline from 502,366 recruited. An AL score was assembled from 12 routinely measured biomarkers. Incident CVD was ascertained via linkage to hospital and mortality records. We estimated adjusted hazard ratios (HRs) using Cox models and assessed nonlinearity with restricted cubic splines; robustness was evaluated in prespecified subgroups and sensitivity analyses. We also investigated the role of the mediating effect of inflammatory factors in the AL-CVD relationship. Higher AL tracked with progressively greater CVD risk in a graded, non-linear pattern. Relative to AL = 0, AL> = 6 was associated with HR 2.15 (95% CI 1.99-2.33). Eight inflammatory markers met retention criteria for mediation; neutrophil count mediated 4.73% of the AL-CVD association. Group contrasts across AL tertiles indicated Cohen's d near 0.5 for several markers, largest for no-AL vs. high-AL. Elevated AL is linked to higher incident CVD with a non-linear exposure-response, and neutrophil-centric inflammation accounts for a measurable portion of the association. These findings support integrating stress-biology constructs and inflammatory profiling into cardiovascular risk assessment and prevention frameworks.</p>
14 Authors
- Shuai Xu
- Ge Zhang
- Yudi Xu
- Chaoyang Yu
- Ruhao Wu
- Zhengrui Li
- Teng Li
- Xinyue Cui
- Xufeng Huang
- Shujing Zhou
- Yahui Han
- Haonan Zhang
- Shiqian Zhang
- Yufeng Jiang
1 Application
| Application ID | Title |
|---|---|
| 68136 | Prediction of the risk of morbidity, recurrence and mortality of cardiovascular diseases and cancer: the effect of environmental, clinical and genetic factors |
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