Multimorbidity is associated with risk of incident venous thromboembolism – A nationwide proof-of-concept study

Background: Multimorbidity, i.e. two or more non-communicable diseases (NCDs), has been associated with venous thromboembolism (VTE), but whether multimorbidity is a predictor for incident VTE is unknown. Aims: To examine the associations between multimorbidity and its severity with risk of incident VTE, and examine the association between nine different disease clusters and incident VTE. Methods: A cohort study using landmark analysis of 2,694,442 individuals. Swedish national registers were linked and three landmarks (L1, L2, L3), i.e. baselines, were created with 14-, nine- and four-year follow-up times, respectively. Two or more NCDs defined multimorbidity and ≥5 marked multimorbidity severity. A hazard ratio (HR) with 95 % confidence interval (CI) for VTE was calculated and adjusted for sex, education and year of birth. Death and emigration were treated as competing events. Results: A total of 2,694,442 individuals were included. Multimorbidity was associated with incident VTE in all three analyzed landmarks: adjusted HR for VTE was 2.47 (95%CI 2.24–2.72) for L1, HR was 2.23 (95%CI 2.11–2.36) for L2, and HR was 2.16 (95%CI 2.03–2.29) for L3. HR increased with multimorbidity severity. For instance, HRs for multimorbidity with five or more NCDs was 4.29 (95%CI 2.53–7.28) in L1 analysis, 4.45 (95%CI 3.64–5.45) in L2 analysis and 4.83 (95%CI 4.20–5.55) in L3 analysis. Moreover, seven of nine different multimorbidity disease clusters were predictors for VTE. Conclusion: This study demonstrated proof-of-concept that multimorbidity is a novel dose-graded predictor for VTE. Further studies will determine the usefulness of multimorbidity for VTE prediction in different clinical settings.