Abstract
INTRODUCTION: 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. METHODS: 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, I (2)), publication bias (funnel plot, Egger's test), and risk of bias (ROBINS-I), with sensitivity analysis performed to confirm robustness. RESULT: 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. CONCLUSION: Integrating these biomarkers with traditional risk factors may enable early detection of subclinical atherosclerosis in autoimmune patients, pending further research. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024611894, identifier CRD42024611894.