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.

中文翻译：

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合并症负担和静脉血栓栓塞对死亡率的相互作用：一项全国队列研究

背景 合并症会影响静脉血栓栓塞症 (VTE) 的死亡率，但尚不清楚这是单独的合并症还是存在生物相互作用。目标 我们检查了合并症和 VTE 是否相互作用以增加 VTE 死亡率超过其各自的影响。方法 这项全国性的基于人群的队列研究包括 2000 年至 2016 年期间所有 ≥18 岁的 VTE 患者，以及年龄、性别和合并症匹配的无 VTE 个体的比较队列。我们计算了年龄标准化死亡率，并使用相互作用对比（比率差异的差异）检查了加性量表上的相互作用。结果 30 天随访后，无合并症的个体每 1,000 人年的死亡率在 VTE 中为 419（95% 置信区间 [CI]：391-447），16（95% CI：391-447）13-18）在比较队列中（比率差异：403）。相应的死亡率在 VTE 队列中增加到 591（95% CI：539-643），在低合并症个体的比较队列中增加到 38（95% CI：33-44）（比率差异：553）。相互作用对比 (150) 显示 25% (150/591) 的死亡率可以用低合并症个体的相互作用来解释。对于中度合并症，这一百分比增加到 56%，对于严重合并症，该百分比增加到 63%。在 30 天的随访中，对于年轻个体和不依从抗凝治疗的个体，对于诱发的 VTE，相互作用效应最大。在 31-365 天和 >1-5 年的随访后也观察到相互作用效应的剂量反应模式 (p < 0.0001)。个体合并症之间的交互作用不同。结论 合并症和 VTE 之间的生物学相互作用解释了 VTE 死亡率的很大一部分。相互作用效应随着合并症负担的增加而增加。