Risk of venous thrombosis in persons with increased body mass index and interactions with other genetic and acquired risk factors

Unlabelled Box Essentials • Obesity, factor V Leiden (FVL) and blood group non‐O are common. • We studied the combined effect of these factors on the risk of venous thrombosis (VT). • The combination of obesity, non‐O blood group and FVL increased VT risk up to ten‐fold. • Identifying high VT may be beneficial in thrombosis prevention. Acknowledgements The MEGA study was supported by the Netherlands Heart Foundation (NHS 98.113), the Dutch Cancer Foundation (RUL 99/1992), and the Netherlands Organization for Scientific Research (912‐09‐033/2003). D. D. Ribeiro was financially supported by CAPES (Edital DRI/CGCI no. 006/2009). W. M. Lijfering is a postdoctoral fellow of the Netherlands Heart Foundation (2011T12). Netherlands Heart Foundation NHS 98.113 Dutch Cancer Foundation RUL 99/1992 Netherlands Organization for Scientific Research 912‐09‐033/2003 CAPES 006/2009 Summary: Background Overweight/obesity has a substantial effect on the occurrence of venous thrombosis (VT). Blood group non‐O has a high prevalence in Western populations, and the factor V Leiden mutation could be present in 5% of Caucasians. These frequent prothrombotic risk factors will have a considerable impact on the incidence of VT, especially when combined. Objectives We investigated whether FV Leiden with blood group non‐O modifies VT risk in individuals with different body mass index (BMI) strata in a case–control study (n = 11253). Results We observed a progressively increasing risk of VT with higher BMI, with an odds ratio of 1.9 (95% confidence interval [CI] 1.6–2.3) for those in the upper BMI tertile (BMI > 26.7 kg m−2), as compared with the first BMI tertile (BMI < 23.5 kg m−2, blood group O, and no FV Leiden) (reference group). The addition of FV Leiden and blood group non‐O to the model increased the risk in all BMI tertiles; the odds ratios were 3.8 (95% CI 3.2–4.6) in the third BMI tertile of individuals with blood group non‐O, and 5.4 (95% CI 3.5–8.5) in the third BMI tertile of individuals with FV Leiden. When both FV Leiden and blood group non‐O were present, the odds ratios were 9.1 (95% CI 5.9–14.0) in the first BMI tertile, 9.4 (95% CI 6.6–13.5) in the second BMI tertile, and 12.5 (95% CI 8.9–17.6) in the third BMI tertile. Conclusion Individuals with a high BMI, blood group non‐O and/or FV Leiden have a high VT risk. The high VT risks in some subgroups may justify targeted screening and thromboprophylaxis decisions in these patients.