Abdominal Fat Measures Are Associated With Sex-Specific Prothrombotic Changes in Middle-Aged Adults

A high body mass index is an important risk factor for venous thromboembolism. However, high body mass index does not necessarily reflect an unhealthy body fat distribution. Therefore, we evaluated the association between the amount of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and liver fat content with venous thromboembolism-associated coagulation parameters: plasma levels of factor (F) VIII, FIX, FXI, fibrinogen, and thrombin generation (endogenous thrombin potential and peak thrombin).

In 1759 participants of the NEO study (the Netherlands Epidemiology of Obesity), VAT and abdominal subcutaneous adipose tissue were assessed with magnetic resonance imaging, and liver fat with ¹H-MR spectroscopy. Through linear regression, we examined cross-sectional associations between quartiles of body fat measures and coagulation parameters, stratified by sex and adjusted for relevant confounders.

We found that the amount of VAT was associated with all coagulation parameters in a dose-response manner, with higher levels for individuals in quartile 4 versus 1, ranging between 5.2% (95% CI, -5.8 to 17.4) for FVIII in men and 21.0% (95% CI, 16.7-25.5) for FIX in women. In women, the amount of abdominal subcutaneous adipose tissue was associated with all coagulation parameters, with the highest percentual difference between quartile 4 versus 1 for endogenous thrombin potential 25.4% (95% CI, 13.7-38.4). Liver fat was mostly associated with higher FIX in both sexes, 13.2% (95% CI, 8.6-18.0) in men and 13.6% (95% CI, 10.0-17.4) in women.

The strongest prothrombotic associations were found for VAT. Abdominal subcutaneous adipose tissue contributed only in women, though less strongly than VAT, indicating sex-specific associations. Liver fat was consistently associated with FIX. These findings underscore the importance of body fat distribution and sex in coagulation and thrombotic potential.