# Systematic review and meta-analysis of cardiovascular associated biomarkers in adults with asymptomatic autoimmune diseases

**Authors:** Waiseng U, Lin Hong, Harshawardhan Dhanraj Ramteke, Jiaen Yang, Zhiwei He

PMC · DOI: 10.3389/fcvm.2025.1598590 · Frontiers in Cardiovascular Medicine · 2025-10-16

## TL;DR

This study reviews and analyzes biomarkers that predict cardiovascular disease in adults with autoimmune conditions who show no symptoms.

## Contribution

The study identifies specific biomarkers that may help improve cardiovascular risk assessment in asymptomatic autoimmune patients.

## Key findings

- High-sensitivity C-reactive protein (hs-CRP) is consistently linked to increased cardiovascular risk.
- Lupus anticoagulant, sVCAM-1, and antiphospholipid antibodies show strong predictive value for CVD.
- Some biomarkers like rheumatoid factor and anti-CCP showed inconsistent or borderline results.

## Abstract

Cardiovascular disease (CVD) remains a leading cause of death. Autoimmune patients face heightened CVD risk due to chronic inflammation and immune dysregulation. This systematic review and meta-analysis aim to synthesize current evidence on the predictive value of advanced or novel autoimmune biomarkers for the occurrence of CVD in middle-aged patients with autoimmune diseases and without cardiovascular history or symptoms.

Abstract was registered prospectively (PROSPERO CRD42024611894) and conducted an advanced, MeSH-based search (2004–2025) for studies on autoimmune diseases in adults (18–65) without prior CVD, in various databases. Pooled adjusted hazard ratios were generated using Stata 18, assessing heterogeneity (Cochran's Q, I2), publication bias (funnel plot, Egger's test), and risk of bias (ROBINS-I), with sensitivity analysis performed to confirm robustness.

A comprehensive search in PubMed, Embase, and Medline yielded 3,975 records (after removing 237 duplicates), and after screening 2,488 titles/abstracts and 896 full texts, 69 studies (34 for meta-analysis) with 46,493 participants were included after excluding 188 with pre-existing CVD and 117 with insufficient data. High-sensitivity C-reactive protein (hs-CRP) was consistently associated with elevated CVD risk despite high heterogeneity and potential publication bias. Similarly, lupus anticoagulant, sVCAM-1, and antiphospholipid antibodies demonstrated strong predictive associations. In contrast, rheumatoid factor, anti-CCP, ADMA, homocysteine, NT-proBNP, anti-dsDNA, and TNF-alpha showed borderline significance or inconsistent results. These findings underscore the potential of select inflammatory and immune markers for enhancing CVD risk stratification and guiding targeted prevention strategies.

Integrating these biomarkers with traditional risk factors may enable early detection of subclinical atherosclerosis in autoimmune patients, pending further research.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024611894, identifier CRD42024611894.

Created using Canva, licensed under Free Content License.Infographic summarizing a systematic review and meta-analysis of cardiovascular biomarkers in asymptomatic autoimmune disease patients. From 69 studies reviewed and 34 analyzed, the top predictive biomarkers include lupus anticoagulant, s-VCAM-1, and anti-phospholipid antibodies. A visual flow shows progression from normal autoimmune patients to high cardiovascular risk, use of biomarkers for prediction, lifestyle modifications, and reduced risk of cardiovascular disease.

Created using Canva, licensed under Free Content License.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor)
- **Chemicals:** ADMA (PubChem CID 69048), homocysteine (PubChem CID 778)
- **Diseases:** cardiovascular disease (MONDO:0004995)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** inflammation (MESH:D007249), chronic (MESH:D002908), death (MESH:D003643), autoimmune diseases (MESH:D001327), CVD (MESH:D002318), immune dysregulation (OMIM:614878), lupus anticoagulant (MESH:C531622), atherosclerosis (MESH:D050197)
- **Chemicals:** homocysteine (MESH:D006710), ADMA (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12571752/full.md

## References

104 references — full list in the complete paper: https://tomesphere.com/paper/PMC12571752/full.md

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Source: https://tomesphere.com/paper/PMC12571752