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

Abstract

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/m²) 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.

Keywords:

• venous thromboembolism
• obesity
• exercise
• epidemiology
• surveys and questionnaires

Abbreviations

BMI, body mass index; CCI, Charlson comorbidity index; CI, confidence interval; CPR, civil personal register; DNHSPD, Danish National Health Service Prescription Database; DNPR, Danish National Patient Registry; HR, hazard ratio; ICD-8, International Classification of Diseases, 8th revision; ICD-10, International Classification of Diseases, 10th revision; IR, incidence rate; kg, kilogram; m, metre; MICE, multiple imputation by chained equations; n, sample size; NOAC, non-vitamin K antagonist oral anticoagulants; PY, person-years; VTE, venous thromboembolism.

Ethics Statement

Approval from an ethics committee is not required for registry-based studies.

Data permissions: The study has been reported to the Danish Data Protection Board by Aarhus University.

Patient and Public Involvement: No patient involvement.

Disclosure

The authors report no conflicts of interest in this work. This work was supported by the Department of Clinical Epidemiology, the Danish Heart Foundation (grant number 13-04-R95-A4570-22752), the Department of Clinical Medicine’s travel grant (Aarhus University), and the Foundation of 17-12-1981. MS is supported by the Novo Nordisk Foundation (grant NNF19OC0054908). None of the sponsors had any involvement in the execution of this research project.