| Title: | Enhanced Prediction of Peripheral Artery Disease Using Plasma Proteomics Among Individuals Without Diabetes. |
| Journal: | Journal of the American Heart Association |
| Published: | 6 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42089180/ |
| DOI: | https://doi.org/10.1161/jaha.125.047797 |
Publication 20155
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Although peripheral artery disease (PAD) is an important diabetes complication, a substantial proportion of cases occur among individuals without diabetes. This study aimed to assess the predictive value of plasma proteomics in the long-term risk of PAD among individuals initially free of diabetes.</p>
METHODS: Included were 46 508 participants (6046 with prediabetes) without diabetes or major cardiovascular disease at recruitment of the UK Biobank. Using multivariable Cox regression models, a total of 2923 unique plasma proteins were assessed for the associations with incident PAD. Significant proteins were subsequently processed by a trained light gradient boosting machine classifier to determine important proteins. Using receiver operating characteristic analyses, the performance of these important proteins in predicting incident PAD were evaluated, in the whole sample and by glycemic status (normoglycemia and prediabetes).</p>
RESULTS: During a median follow-up of 12.7 years, 461 participants developed PAD. There were 107 proteins associated with incident PAD, with 103 positive associations. The LGBM approach identified 9 proteins (eg, WFDC2 [WAP 4-disulfide core domain protein 2], MMP12 [macrophage metalloelastase], and GDF15 [growth differentiation factor 15]) as the top-ranked proteins based on their importance ordering. Whereas glycated hemoglobin showed very modest predictive accuracy, a panel incorporating these top proteins showed good performance in the prediction of PAD risk (area under the curve 0.820), and it significantly enhanced the prediction beyond traditional risk factors (raising area under the curve from 0.803 to 0.837, DeLong test P=5.21×10-3). These observations were consistent for participants with normoglycemia or prediabetes.</p>
CONCLUSIONS: Plasma protein biomarkers enhance the prediction of long-term risk for PAD among individuals without diabetes, regardless of glycemic status.</p>
15 Keywords
- Aged
- Biomarkers
- Blood Proteins
- Female
- Humans
- Incidence
- Male
- Middle Aged
- Peripheral Arterial Disease
- Prediabetic State
- Predictive Value of Tests
- Proteomics
- Risk Assessment
- Risk Factors
- United Kingdom
10 Authors
- Meng-Yuan Miao
- Jie-Qiong Lyu
- Fei Fang
- Zhong-Yue Liu
- Miao Xu
- Hong-Jun Zhang
- Xing-Qiang Pan
- Li-Qiang Qin
- Hai-Peng Wang
- Guo-Chong Chen
1 Application
| Application ID | Title |
|---|---|
| 90087 | Role of environmental and host factors and their interplays in the development and progression of chronic diseases |
Enabling scientific discoveries that improve human health