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Background/Purpose: Individuals who later developed rheumatoid arthritis (RA) have increased levels and frequencies of risk factors for cardiovascular disease (CVD), years before onset of RA. The relationships between CVD risk factors and inflammatory markers, i.e., cytokines and chemokines, were analysed in individuals prior to onset of symptoms and compared with controls. Methods: A case-control study was based on population surveys from The Västerbotten Intervention Programme (VIP) and the WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) with data collected on socioeconomic and lifestyle factors, BMI, waist, blood pressure, and blood samples by a nurse. The register of patients with RA (ARA criteria) was co-analysed with the registers from the Medical Biobank and 469 pre-symptomatic individuals (median age 50.2 years; 67.8% women, median predating time 5.0 (IQR; 2.0-8.0) years), and 234 controls (median age 50.3 years; 67.1% women) were identified. CVD risk factors were defined as: hypertension (treatment or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg), elevated ApoB/ApoA1 ratio (women ≥0.7, men ≥0.8, including lipid lowering treatment), BMI ≥25kg/m2, diabetes, and ever being smoker. Concentrations of eotaxin, interferon gamma-induced protein (IP-10), monocyt-chemoattractant protein 1 (MCP1), macrophage derived chemokine (MDC), interleukin (IL) 2, IL-4, IL-6, IL-8, and IL-10, were analysed in plasma using R&D systems' assays (Minneapolis, MN) according to the manufacturer's instructions. Results: Pre-symptomatic individuals had significantly higher levels of IL-6 compared with controls, both in women and men. IL-10 was significantly higher in pre-symptomatic men compared with controls. Cytokines/chemokines were significantly associated with the CVD risk factors in the cases e.g. IL-6 with each of the risk factors, eotaxin with smoking, IP-10 with increased BMI, being diabetes or having hypertension, whilst MDC was associated significantly with smoking and BMI≥25 kg/m2. After adjustments for sex and age only eotaxin concentrations were significantly associated with being ever smoker. In women, MDC was significantly associated with smoking, BMI≥25 kg/m2 and diabetes. Having the combination of several CVD risk factors was associated with significantly higher concentrations of MCP-1, MDC, and IL-6 in pre-symptomatic women. IL-6 increased further the relative risk in combinations with all CVD risk factors for the pre-symptomatic cases compared with controls. Conclusion: Increased concentrations of cytokines/chemokines were associated with CVD risk factors to a higher extent among the pre-symptomatic RA cases compared with controls. The pattern of association varied between the risk factors and the sex of the cases.