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Background and Importance Patients with rheumatoid arthritis (RA) are at higher risk of cardiovascular disease (CVD) due to systemic inflammation and treatment-related factors. The JAK/STAT signalling pathway plays a central role in immune modulation. Genetic variability in this pathway may influence cardiovascular outcomes during treatment in RA patients.Aim and Objectives To evaluate the potential association between five single nucleotide polymorphisms (SNPs) (rs10119004, rs7857730, rs2274472, rs2230722, rs2230724) in JAK2 gene involved in the JAK/STAT pathway and the development of cardiovascular disease during treatment in patients diagnosed with RA.Material and Methods Ambispective observational cohort study in 115 RA patients who had been treated with JAKi. Genotypes were determined by Taqman PCR Real Time. Quantitative variables: age, body mass index (BMI), disease duration, previous biologic therapies (BTs), Charlson Comorbidity Index (CCI). Qualitative variables: sex, first JAKi used, rheumatoid factor, anti-cyclic citrullinated peptide antibody (ACPA, development of CVD during treatment, previous hypertension or antihypertensive treatment. Data were collected from electronic prescriptions and medical records, and analysed with R Commander. A retrospective bivariate analysis was conducted on genotyped patients. The occurrence of cardiovascular disease during treatment was analysed against specific SNP genotypes using Fisher’s exact test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of associations.Results 115 patients were analysed; 94 women (81.7%) median age 43 years [33–51] and median disease duration of 12 years [8–20]. Most patients were ACPA-positive (82.6%) and RF-positive (74.8%). Median CCI was 1.5 [0–3], and median BMI 27.3 [24.3–31.2]. Patients had received two prior biologic therapies [1.0-3.2] with median treatment duration 21 months [13-40]. Previous hypertension was present in 34 patients (29.5%) with 29 (25.2%) receiving antihypertensive therapy prior to JAKi treatment. The bivariate analysis revealed that patients with rs2230722 SNP in JAK2 gene showed a statistically significant association with cardiovascular outcomes. Patients carrying the T allele had a notably lower risk of developing cardiovascular disease compared to those with the C allele (p = 0.002; OR = 8.44; 95% CI 95%: 2.26–55.02).Conclusion and Relevance Our findings suggest that certain polymorphisms within the JAK/STAT pathway, may influence the risk of CVD during treatment. These preliminary results support further investigation into pharmacogenetic profiling as a tool to stratify cardiovascular risk in RA patients and guide personalised therapeutic strategies.Conflict of Interest No conflict of interest