The Risk for Venous Thrombosis in Patients with Increased Body Mass Index and Interactions with Other Genetic and Acquired Risk Factors: The MEGA Study

Obesity (prevalence of 20–25% in Western populations), blood group non-O (present in 50% of Western populations) and factor V Leiden (present in 5% of Caucasian populations) are frequent prothrombotic risk factors and may therefore have a considerable impact on the overall incidence of venous thrombosis. We previously reported that the increased risk of venous thrombosis in individuals with a high BMI is mediated by factor VIII induced APC-resistance, and that the combination of blood group non-O with a high BMI or factor V Leiden leads to higher venous thrombosis risks than expected when these prothrombotic factors are analyzed separately (ASH Annual Meeting Abstracts. 2009;114:453). However, small numbers did not enable us to sufficiently study the risk of venous thrombosis for the combination of a high BMI with factor V Leiden and blood group non-O, or to study these effects in subgroups.

To investigate whether the presence of factor V Leiden with blood group non-O can modify the risk for venous thrombosis in individuals with different body mass index strata in a larger population based study than previously reported. To evaluate the presence of gene-environment interactions in specific subgroups.

MEGA study: 4956 consecutive patients aged 18–70 years with a first episode of venous thrombosis, and 6297 age- and sex-matched controls were included. Information about BMI, blood group and factor V Leiden was available in 4062 patients and 4659 controls. Odds ratios for venous thrombosis and their 95% confidence intervals (95% CIs) were calculated for BMI tertiles with logistic regression and adjusted for age and sex (matching factors). An interaction analysis among the BMI tertiles, factor V Leiden and blood group non-O was performed. Subgroup analyses involved stratification by venous thrombosis place (i.e. deep vein thrombosis or pulmonary embolism), sex, and presence or absence of acquired venous thrombosis risk factors.

A progressive increase in BMI was associated with an increased risk for venous thrombosis, odds ratios 1.1 (95% CI, 0.9–1.3) for those with a BMI in the median tertile, and 1.9- (95% CI, 1.6–2.3) for those in the upper tertile, as compared to individuals in the first BMI tertile, blood group O, and no factor V Leiden (i.e. the reference group). The addition of factor V Leiden and blood group non O in the model increased the risk in all BMI tertiles; odds ratios for venous thrombosis 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 factor V Leiden, respectively. When both factor V Leiden and blood group non-O were present, odds ratios for venous thrombosis 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 BMI third BMI tertile as compared to the reference group. Subgroup analyses revealed similar joint interactions of BMI with blood group non-O and factor V Leiden on venous thrombosis risk.

No relevant conflicts of interest to declare.