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The Interaction Effect between Comorbidity Burden and Venous Thromboembolism on Mortality: A Nationwide Cohort Study
Kasper Bonnesen1, Morten Schmidt1,2, Erzsébet Horváth-Puhó1
1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Background:
Comorbidity influences venous thromboembolism (VTE) mortality, but it is unknown whether this is due to comorbidity alone or whether biological interaction exists.
Objectives:
We examined whether comorbidity and VTE interact to increase VTE mortality beyond their individual effects.
Methods:
This nationwide population-based cohort study included all VTE patients ≥18 years during 2000 to 2016, and an age-, sex-, and comorbidity-matched comparison cohort of individuals without VTE. We computed age-standardized mortality rates and examined interaction on the additive scale using interaction contrasts (difference in rate differences).
Results:
After 30-day follow-up, the mortality rate per 1,000 person-years among individuals with no comorbidity was 419 (95% confidence interval [CI]: 391-447) in the VTE and 16 (95% CI: 13-18) in the comparison cohort (rate difference: 403). The corresponding mortality rate increased to 591 (95% CI: 539-643) in the VTE cohort and 38 (95% CI: 33-44) in the comparison cohort among individuals with low comorbidity (rate difference: 553). The interaction contrast (150) showed that 25% (150/591) of mortality was explained by the interaction in individuals with low comorbidity. This percentage increased to 56% for moderate and 63% for severe comorbidity. Interaction effects were largest within 30-day follow-up, for provoked VTE, in young individuals, and in individuals noncompliant to anticoagulant therapy. Dose-response patterns for interaction effects were also observed after 31-365-day and >1-5-year follow-up (p < 0.0001). Interaction effects varied between individual comorbidities.
Conclusion:
Biological interaction between comorbidity and VTE explained a substantial proportion of VTE mortality. The interaction effect increased with comorbidity burden.
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