Estimated lifetime risk of venous thromboembolism in men and women in a Danish nationwide cohort: impact of competing risk of death.

Incidence of venous thromboembolism (VTE) risk varies by age and sex. Some studies have reported overall higher risk in men, especially when VTEs triggered by female reproductive factors are excluded. However, higher mortality rates in men may have led to overestimation of lifetime VTE risk in men compared with women. Therefore, we estimated the lifetime risk of VTE in men and women in a Danish, nationwide cohort, taking into account the competing risk of death. Within the population of Denmark (> 5 million persons), all first-time VTEs occurring in 1995-2016 were identified from the Danish National Patient Registry covering all Danish hospitals. The cumulative incidences of VTE were estimated in men and women with age as timescale, taking into account the competing risk of death. Estimated lifetime risk was defined as cumulative incidence at age 100. In a simulation study, we excluded the proportion of female cases that could be attributed to reproductive risk factors and re-estimated the cumulative incidence. We identified 123,543 incident VTEs. The cumulative incidence of VTE was 1.9% in women and 1.3% in men at age 50, 4.3% in women and 4.4% in men at age 70, and 9.3% in women and 8.1% in men at age 100. After accounting for VTEs attributed to reproductive factors, the corresponding incidences in women were 1.2% at age 50, 3.2% at age 70, and 8.2% at age 100. In conclusion, the estimated lifetime risk of VTE was slightly higher in women than in men when accounting for competing risk of death. Our simulation study suggested that reproductive risk factors contribute modestly to the estimated lifetime VTE risk in women.

The Risk of Venous Thromboembolism Attributed to Established Prothrombotic Genotypes.

BACKGROUND: The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. METHODS: Cases with incident VTE (n = 1,493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health (HUNT) study (1995-2008). DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population-attributable fractions (PAFs) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one by one in ranked order of the individual PAFs. RESULTS: Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11], and rs8176719 [ABO]). The cumulative PAF for the six-SNP model was 45.3% (95% CI: 19.7-71.6) for total VTE and 61.7% (95% CI: 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for deep vein thrombosis (DVT; 52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged ≥70 years (24.9%). CONCLUSION: Our findings suggest that 45 to 62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly.