Novel Biomarkers and Advanced Imaging in Cardiovascular Risk Stratification for Rheumatic Diseases

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Abstract
Rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), significantly increase the risk of cardiovascular disease (CVD), with affected patients exhibiting a 2-3-fold higher risk compared to the general population. This elevated risk is primarily driven by chronic inflammation and accelerated atherosclerosis, which are not fully captured by traditional cardiovascular risk calculators. RA patients face cardiovascular risks similar to those of type 2 diabetics, while SLE patients, particularly young women, have a dramatically increased risk of myocardial infarction. These conditions challenge the conventional understanding of CVD risk, as traditional factors like hypertension, dyslipidemia, and smoking do not fully account for the excess risk observed. This has led to growing interest in the use of new biomarkers and advanced imaging technologies to improve risk stratification and early detection of cardiovascular involvement. This review examines the pathophysiological mechanisms that link rheumatic diseases with cardiovascular risk. Chronic inflammation, immune dysregulation, and vascular dysfunction are central to the accelerated atherosclerosis and myocardial damage seen in RA and SLE. Key proinflammatory cytokines, including Tumor Necrosis Factor- Alpha (TNF-α), Interleukin (IL) IL-6, and IL-17, contribute to endothelial dysfunction and oxidative stress, exacerbating cardiovascular risk. In addition, biomarkers such as high-sensitivity C-reactive protein (hs-CRP), NT-proBNP, and troponins are valuable for detecting subclinical cardiac involvement and predicting adverse cardiovascular outcomes. Emerging biomarkers like IL-32, Dickkopf-related protein 1 (DKK-1), and galectin-3 also show potential in further refining risk assessment, particularly for atherosclerosis and myocardial fibrosis in rheumatic diseases. Advanced imaging methods, such as transthoracic echocardiography (TTE), carotid ultrasonography, cardiac MRI (CMR), and coronary CT angiography (CCTA), provide key insights into subclinical cardiovascular changes in rheumatic disease patients. These techniques enable the detection of myocardial inflammation, fibrosis, and early atherosclerosis, helping guide clinical decisions and preventive interventions. Despite advancements, traditional cardiovascular risk calculators often underestimate CVD risk in rheumatic disease patients, leading to the use of adjusted models, such as EULAR-endorsed 1.5× risk multiplier for RA patients. These adjustments, along with the integration of biomarkers and imaging findings, can help identify high-risk individuals and prompt early interventions, such as statin therapy. However, challenges remain, including the cost and accessibility of some imaging methods, the heterogeneous risk profiles across different rheumatic diseases, and the need for more prospective trials to evaluate the effectiveness of biomarkers and imaging in clinical practice. In conclusion, incorporating biomarkers and advanced imaging techniques into cardiovascular risk assessment provides a more accurate method for managing CVD in rheumatic disease patients. These approaches allow for more personalized care, helping reduce the increased CVD mortality seen in this population. Future research should focus on refining multi-biomarker algorithms, improving imaging technology, and conducting intervention trials to optimize cardiovascular outcomes in rheumatic disease patients.

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