Aim: to systematize current data on the role of vascular comorbidity as a systemic factor in the pathogenesis, diagnosis, and treatment of synovitis to optimize management of patients with combined pathology. Materials and methods. Publications from PubMed/MEDLINE, Cochrane Library, and Google Scholar databases for 2000–2025 were analyzed, systematizing epidemiological data, molecular mechanisms of pathogenesis, diagnostic algorithms, and therapeutic strategies for synovitis with vascular comorbidity, with emphasis on Eastern European specificity. Results. Epidemiological studies confirm bidirectional associations: in women, arterial hypertension is associated with knee osteoarthritis (OR 2.27; 95% CI 1.17–4.39), while in inflammatory arthritis, overall cardiovascular risk increases by 35% (RR 1.35; 95% CI 1.12–1.63) and myocardial infarction risk by 43% (RR 1.43; 95% CI 1.29–1.57). The molecular basis involves convergence of pathogenic pathways: endothelial dysfunction with reduced nitric oxide bioavailability, NF-κB signaling activation with adhesion molecule expression (ICAM-1, VCAM-1), and pathological VEGF-dependent angiogenesis. Integrated diagnostic approaches include biomarkers (VEGF with activity correlation r=0.72, soluble adhesion molecules) and imaging modalities (MRI using RAMRIS system with 95% sensitivity and histological correlation r=0.85). The therapeutic paradox of nonsteroidal anti-inflammatory drugs involves 10–50% cardiovascular risk elevation even with short-term use, justifying patient stratification by risk level. Colchicine demonstrates dual benefit, reducing cardiovascular events by 49–67% in coronary artery disease. Subclinical synovitis persists in 45–50% of patients with vascular comorbidity compared to 27–31% without. Conclusion. Vascular comorbidity fundamentally modifies synovitis pathogenesis, diagnosis, and therapeutic response through molecular mechanism convergence. Personalization of treatment strategies considering cardiovascular profile and integration of vascular protection into treatment protocols should become standard clinical practice, especially for the high-risk Eastern European population.