Introduction: Some rheumatologic diseases, including rheumatoid arthritis and systemic lupus erythematosusa are associated positively with occurrence of venous thromboembolism (VTE). Chronic inflammation accompanying these rheumatologic diseases is considered to increase the risk of VTE. Gout, which is caused by hyperuricemia, is the most common rheumatologic inflammatory arthritis. In addition, hyperuricemia, itself, has proinflammatory effects on vascular cells. Hyperuricemia and gout therefore may increase the risk of VTE, but, so far there has been no study investigating these associations.
Hypothesis: We assessed the hypothesis that hyperuricemia or gout are positively associated with the risk of VTE.
Methods: The Atherosclerosis Risk in Communities Study measured serum uric acid (SUA) in 15,063 men or women, aged 45-64, without history of VTE or anticoagulant use and followed them for VTE from 1987 to 2011. Of these participants, 10,982 men or women provided information on gout history. Hazard ratios (HRs) of VTE were estimated using Cox proportional hazards models adjusted for age, sex, race, center, body mass index, diabetes, smoking, eGFR, vonWillebrand factor, factor VIII, and gout medication across levels of SUA [median (range) mg/dL: 4.6 (≤5.2), 5.7 (5.2-6.2), 6.7 (6.2-7.2), 7.7 (7.2-8.2), 8.5 (8.2-8.9), and 9.6 (≥8.9)] or gout history (yes or no).
Results: We documented 688 incident VTEs [265 unprovoked and 423 provoked VTEs (232 not cancer related and 191 cancer related VTEs)]. Age, sex, and race-adjusted HRs [95% confidential interval (CI)] for total VTE were 1.00, 1.31 (1.04-1.65), 1.34 (1.05-1.70), 1.81 (1.39-2.35), 1.81 (1.25-2.60), and 2.85 (2.06-3.95) (P for trend<0.001) across levels of SUA. After adjustment for the other VTE risk factors, those in the highest vs. lowest level of SUA had HRs (95% CI; P for trend) of 1.72 (1.22-2.45; 0.006) for total VTE, 1.83 (1.08-3.09; 0.128) for unprovoked VTE, and 1.61 (1.00-2.58; 0.022) for provoked VTE. On the other hand, we observed no significant association between the gout history and the incidence of VTE.
Conclusions: In conclusion, elevated SUA was associated with a higher risk of VTE, suggesting that elevated SUA might be a novel risk factor for VTE.