Abdominal Obesity, IL-6 Levels and the Risk of Venous Thromboembolism Among Women: a Case-Control Study

abdominal obesity is one of the components of the metabolic syndrome (MS), which is a cluster of cardiovascular risk factors. Recent prospective studies demonstrated that among the components of the MS, abdominal obesity was the only independent risk factor for venous thromboembolism (VTE). However, it remains unclear to what extent inflammation contributes to the risk of VTE from abdominal obesity. The aim of this study was to investigate the association of abdominal obesity and VTE in women and the effect of inflammation on this association.

94 female patients were included with a first objectively confirmed episode of VTE, with a median age of 39 years (range: 21–60). Exclusion criteria were malignancy, autoimmune diseases, chronic renal or liver diseases and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Controls were comprised of 100 healthy women, with a median age of 37 years (range: 18–63), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age. Waist circumference (WC) was measured at the umbilical line. A WC ≥ 88 cm in women defined abdominal obesity according to the National Cholesterol Education Program. Plasma level of IL-6 was measured by a highly sensitive ELISA, fibrinogen by Clauss method and high-sensitive C-reactive protein (CRP) by immunoturbidimetry. High levels of IL-6 (> 2.01 pg/mL), CRP (> 6.66 mg/L) and fibrinogen (> 3.59 g/L) were dichotomized at the 90^th percentile of the control values.

median WC was higher in patients (89 cm; range: 65–126) than in controls (84 cm; range: 62–131), P<0.01. In both groups, WC significantly correlated (P<0.01) with body mass index as expected, but also with age, fibrinogen, CRP and IL-6. Fifty-five patients and 43 controls had abdominal obesity, yielding an odds ratio (OR) of 1.87 [95% Confidence Interval (CI) 1.06 – 3.31]. The association of VTE and abdominal obesity was not affected after adjustment for potential confounders, as high levels of CRP (OR 1.86; 95% CI 1.05 – 3.30) and fibrinogen (OR 1.94; 95% CI 1.08 – 3.48), and it was of borderline significance when adjusted for age (OR 1.76; 95% CI 0.97–3.20). However, the risk was no longer significant after adjustment for high levels of IL-6 (OR 1.57; 95% CI 0.87–2.84). Simultaneous adjustment for age and high levels of CRP, fibrinogen and IL-6 yielded an OR of 1.60 (95% CI 0.85 – 3.00). The impact of abdominal obesity on the risk of VTE was more pronouncedly affected when IL-6 entered into the logistic regression model as a continuous variable (OR 1.33; 95% CI 0.72 – 2.47). Conversely, high IL-6 levels increased the risk of VTE even after adjustment for age, abdominal obesity and high levels of CRP and fibrinogen (OR 3.65; 95%CI 1.56 – 8.50).

in this study abdominal obesity was associated with VTE in crude analysis in a relatively young population composed of women. However, the association was no longer significant after adjustment for IL-6. There is evidence that visceral adipose tissue, assessed by WC, is metabolic active, releasing cytokines. To our knowledge this is the first study that evaluated in the same population the effect of IL-6 and abdominal obesity on the risk of VTE. More data, including prospective studies, are required to elucidate the role of inflammation in the association of VTE and abdominal obesity.

This study was supported by FAPESP (2005/56799-0).

No relevant conflicts of interest to declare.