Linda Flinterman and colleagues report on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event.

Summary.  Venous thrombosis of the upper extremity is a rare disease. Therefore, not as much is known about risk factors, treatment and the risk of recurrence as for venous thrombosis of the leg. Only central venous catheters and strenuous exercise are commonly known risk factors for an upper extremity venous thrombosis. In this review an overview of the different risk factors, possible treatments and the complications for patients with a venous thrombosis of the upper extremity is given.

AbstractRisk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.

To cite this article: Timp JF, Lijfering WM, Flinterman LE, van Hylckama Vlieg A, le Cessie S, Rosendaal FR, Cannegieter SC. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost 2015; 13: 1823-32.Summary. Background: Prediction of recurrent venous thrombosis remains a challenge in the clinic. Objective: To investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis. Patients/methods: Patients, aged 18-70 years with a first venous thrombosis, were followed from discontinuation of anticoagulant treatment (1999-2010 MEGA follow-up study). The levels of FVIII activity, FVIII antigen and von Willebrand factor (VWF) antigen were measured at least 3 months after cessation of anticoagulant treatment. Results: Of 2242 patients followed for a median of 6.9 years, 343 developed recurrent thrombosis (incidence rate 2.7/100 patient-years; 95% confidence interval [CI] 2.5-3.1). Recurrence rates steadily increased with higher FVIII activity levels, from 1.4 (95% CI 1.0-1.9), 2.3 (95% CI 1.8-2.9), 3.0 (95% CI 2.4-3.7), 3.2 (95% CI 2.5-4.1), 3.9 (95% CI 2.8-5.3) to 5.1 (95% CI 3.8-6.8) per 100 patient-years, for levels ranging from < 100 IU dL À1 to > 200 IU dL À1. Patients in the highest category of FVIII (> 200 IU dL À1 ) had a three-fold higher recurrence rate than patients in the lowest category (≤ 100 IU dL À1 ) (hazard ratio 3.4; 95% CI 2.2-5.3).Results were similar for FVIII antigen and VWF antigen levels, in several sensitivity analyses, and FVIII predicted recurrence rates over a long time period. Within subgroups of patients currently assumed to have low recurrence risks, a high level of FVIII was still predictive for recurrences. Adding FVIII to an existing prediction model (DASH score) improved its predictive value, and, after replacement of D-dimer with FVIII, the model performed equally well, if not better. Conclusions: FVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools.

Venous thrombosis and arterial thrombosis are traditionally regarded as two different diseases with respect to pathophysiology, epidemiology, and treatment strategies. Research findings of the past few years suggest that this categorical distinction may be too strict. However, whether the described relationship between venous and arterial thrombosis is real or a result of other factors such as confounding, chance, or bias is still unclear. In this review, we discuss the current literature while using causal diagrams to better understand possible causal relations between cardiovascular risk factors, atherosclerosis, arterial thrombosis, and venous thrombosis. Furthermore, we propose study designs to investigate the causal link between venous and arterial thrombosis. In addition, we comment on the effect of statin use on the occurrence of both arterial and venous thrombosis. The possible clinical implications of these findings are discussed.

Background-Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population. Methods and Results-In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69-6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32-3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients. Conclusions-Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE. (Circulation. 2014;129:855-863.)

To cite this article: Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. Body height, mobility, and risk of first and recurrent venous thrombosis. J Thromb Haemost 2015; 13: 548-54.Summary. Background: Tall people have an increased risk of a first venous thrombosis. Sedentary lifestyle has been shown to act synergistically with body height, especially during long-haul flights. Objective: To estimate the relation between height and risk of a first and recurrent venous thrombosis and a possible additional association with a mobile or an immobile lifestyle. Methods: Patients with a first venous thrombosis and control subjects were included between 1999 and 2004 (MEGA case-control study). Patients were followed for recurrence for an average time of 5.1 years (MEGA follow-up study). Odds ratios and hazard ratios (HRs) per increase of 5 cm were calculated compared with a height of 165-170 cm, separately and in combination with (im)mobility. Results: In 4464 patients who reported their height, we found an increasing risk of a first and recurrent event with height. For men, a 2.9-fold (95% confidence interval [CI] 1.9-4.4) increased risk for first venous thrombosis was found for those between 195 and 200 cm and a 3.8-fold (95% CI 1.5-9.8) higher risk for those > 200 cm compared with the reference category. For recurrence risk, the HRs were 1.7 (95% CI 0.8-3.3) and 3.7 (95% CI 1.4-10.0), respectively. For women, a 1.5-fold (95% CI 0.7-3.4) and 3-fold (95% CI 0.9-9.4) increased risk was found for those > 185 cm for first and recurrent venous thrombosis, respectively. For the tallest men and women, a slight additionally increased risk was observed for sedentary lifestyle. Conclusions: Tall men and women have an increased risk of first and recurrent venous thrombosis, possibly higher in combination with a sedentary lifestyle.

Key Points• Patients with VT have an increased risk of subsequent CVD compared with control participants.• The increased risk of CVD in these patients can be explained by etiologic factors leading to both diseases.Patients with venous thrombosis (VT) have an increased risk of subsequent CVD (CVD), but the underlying pathophysiology is unclear. Using data from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis follow-up study, 4480 patients with VT, 2926 partner control participants, and 2638 random digit dialing (RDD) control participants were followed-up between 1999 and 2008. Incidence rates and hazard ratios with 95% confidence intervals (95% CIs) of CVD (defined as myocardial infarction or ischemic stroke) were calculated for patients vs controls. Measurable confounders (age, sex, body mass index, smoking, chronic disease, malignancy, genetic thrombophilia, and procoagulant markers) were adjusted for when comparing patients with RDD controls. Unmeasured lifestyle-related factors were also considered by comparing patients with their partners. During a median follow-up time of 5 years, 124 CVD events occurred. Incidence of CVD per 1000 person-years was 3.2 (95% CI, 2.5-4.0) in patients, 2.2 (95% CI, 1.5-3.0) in partners, and 1.6 (95% CI, 0.9-2.6) in RDD controls. Crude hazard ratio was 2.2 (95% CI, 1.2-3.8) in patients compared with RDD controls and 1.5 (95% CI, 1.0-2.3) in patients compared with partners. After adjustment for all confounders, these risks attenuated to 1.8 (95% CI, 0.8-4.2) and 1.3 (95% CI, 0.7-2.5) for patients compared with RDD control participants and partners, respectively. In conclusion, individuals with VT had an increased risk of CVD. This could be explained by common etiologic factors. (Blood. 2013;121(24):4948-4954)