Physical Activity as an Effect Modifier of the Association Between Obesity and Venous Thromboembolism: A Danish Population-Based Cohort Study

PURPOSE: Obesity is an established risk factor for venous thromboembolism (VTE), while studies on physical inactivity and VTE risk show conflicting results. We examined whether physical activity modified the association between obesity and VTE. PATIENTS AND METHODS: We conducted a population-based cohort study by combining data on outcome diagnoses, comorbidities and medication from nationwide registries with self-reported lifestyle data from an extensive Danish lifestyle questionnaire (2001–2015). We computed incidence rates (IRs) and hazard ratios (HRs) of VTE for categories of body mass index (BMI), among the total study population (n=57,523) and for physically active (n=25,387) and inactive individuals (n=30,902) separately. RESULTS: Obesity (BMI ≥30 kg/m(2)) was as expected associated with increased VTE risk compared with normal weight (HR 1.62, 95% confidence interval (CI): 1.26–2.09). Independent of BMI category, the rate of VTE was higher for inactive than active individuals. Thus, among obese individuals, the IR per 1000 person-years was 2.03 (95% CI: 1.60–2.57) for inactive and 1.44 (95% CI: 0.97–2.15) for active individuals. In contrast, the HR for VTE comparing obese with normal weight individuals were higher for active (HR 2.19, 95% CI: 1.35–3.58) than inactive individuals (HR 1.36, 95% CI: 1.00–1.84). CONCLUSION: Physical activity acts as an effect measure modifier of the association between obesity and VTE. Thus, physical activity reduced the absolute rate of VTE among obese individuals but increased the relative rate of VTE among obese compared with normal weight individuals.