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Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease with a high recurrence rate. There is a risk of chronic complications affecting health- related quality-of life (QoL). Aim: To evaluate long-term consequences of VTE in women and to study and to explore the risk factors for recurrent event, arterial cardiovascular disease (CVD), mortality, post- thrombotic syndrome (PTS) and QoL. Methods: We performed a cohort study inviting 1433 women with a previous episode of VTE (exposed) and 1402 women without VTE (unexposed). The cohort was derived from the ‘Thrombo Embolism Hormone Study’ (TEHS), a Swedish nation-wide case-control study on risk factors for VTE, recruiting women 2002 - 2009. During 2011 all women were followed up through a mailed questionnaire, including questions on life-style factors, recurrent VTE and inquiries according to the QoL instrument SF-36. To assess disease specific QoL, exposed women were also asked questions according to VEINES-Sym / VEINES-QoL. A modified Villalta scale was applied to evaluated PTS. Information on CVD and mortality was obtained through the Patient Register and the Cause of Death Register. Baseline data on life style factors, risk factors for VTE, including hormone treatment and family history of VTE and CVD were collected through a telephone interview within three months after the diagnosis of VTE for the exposed, or at time of inclusion in TEHS for unexposed. Blood samples for DNA-analyses were collected at time of inclusion in TEHS. Result: A total of 2117 women (1087 (75%) exposed and 1030 (73%) unexposed) accepted participation in the study. During a median follow-up of 5 years (range 0.1-9.1), 10 % of exposed women had a recurrent event. The risk of recurrence was highest among women with unprovoked VTE and obesity. Women with hormone-induced VTE had a lower risk of recurrence than women with unprovoked VTE but not as low as women with surgery/cast induced VTE. Women carrying the risk

Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95 % CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95 % CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95 % CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction., QC 20160303