A recent study published in the Journal of Cellular and Molecular Medicine has shed light on the relationship between interleukin-6 (IL-6) and cardiovascular disease (CVD) risks in patients with rheumatoid arthritis (RA).
The findings revealed that IL-6 levels were significantly higher in both early and late-stage RA patients compared to the control group. These elevated levels were positively correlated with several CVD predictors, including the Disease Activity Score (DAS-28), blood pressure, systematic Coronary Risk Evaluation (SCORE)., and Framingham Risk Score (FRS). Interestingly, a negative association was found between IL-6 and high-density lipoprotein (HDL), a factor typically linked to reduced cardiovascular risk. Moreover, IL-6 was also found to have a positive correlation with HS-CRP and NT-proBNP, biomarkers that are indicative of inflammation and heart strain, respectively. Additionally, the study highlighted a notable association between IL-6 and the CXCL9-CXCR3 axis, further underlining its involvement in the inflammatory process.
IL-6, a key pro-inflammatory cytokine in RA pathophysiology, is markedly elevated in RA patients’ serum and synovial fluid and is strongly associated with joint damage and disease activity. Its elevated expression is closely linked to the development of cardiovascular disorders such as atherosclerosis, myocardial infarction, heart disease, and ischemic stroke.IL-6 contributes to CVD by stimulating the production of acute-phase reactants like C-reactive protein (CRP), activating the coagulation cascade, impairing endothelial function, and driving persistent inflammation. It also affects lipid metabolism, thereby accelerating CVD onset and progression. In high-risk individuals, IL-6 is a strong predictor of long-term cardiovascular events and mortality, particularly in those with stable coronary disease and elevated risk of cardiovascular complications. Its role highlights the connection between chronic inflammation and cardiovascular health, positioning IL-6 as a critical biomarker for CVD risk in RA patients.
CVS poses a significant burden for patients with RA, who are at a 1.5- to 2-fold higher risk of developing cardiovascular events like heart attacks, strokes, and heart failure compared to the general population. Additionally, RA patients frequently experience higher rates of hypertension, diabetes, obesity, and dyslipidemia, which further elevate cardiovascular risk. Certain RA medications, such as corticosteroids, can exacerbate these risks, while disease-modifying antirheumatic drugs (DMARDs), especially biologics, may reduce cardiovascular risk by controlling inflammation. Furthermore, RA patients often present with atypical CVD symptoms, leading to delayed diagnosis and less aggressive treatment, contributing to poorer outcomes. Early identification and comprehensive management of both RA and cardiovascular risks are essential to reduce this burden.
The current findings suggest that IL-6 could serve as a potential biomarker for assessing cardiovascular risk in RA patients, offering clinicians a new tool for predicting future cardiovascular events. As cardiovascular disease remains a significant concern for RA patients, this research opened new avenues for risk stratification and early intervention. Further studies were expected to validate these findings and explore the potential clinical applications of IL-6 as a biomarker in rheumatoid arthritis management.
Reference
Roghani SA, Shamsi A, Jalili C, Jalili F, Lotfi R, Garman N, et al. Interleukin-6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients. J Cell Mol Med. 2024 Aug;28(16):e70028.