Background: Estimates of the incidence of venous thrombosis (VT) vary, and data on mortality are limited. Objectives: We estimated the incidence and mortality of a first VT event in a general population. Methods: From the residents of Nord-Trøndelag county in Norway aged 20 years and older (n = 94 194), we identified all cases with an objectively verified diagnosis of VT that occurred between 1995 and 2001. Patients and diagnosis characteristics were retrieved from medical records. Results: Seven hundred and forty patients were identified with a first diagnosis of VT during 516 405 person-years of follow-up. The incidence rate for all first VT events was 1.43 per 1000 person-years [95% confidence interval (CI): 1.33–1.54], that for deep-vein thrombosis (DVT) was 0.93 per 1000 person-years (95% CI: 0.85–1.02), and that for pulmonary embolism (PE) was 0.50 per 1000 person-years (95% CI: 0.44–0.56). The incidence rates increased exponentially with age, and were slightly higher in women than in men. The 30-day case-fatality rate was higher in patients with PE than in those with DVT [9.7% vs. 4.6%, risk ratio 2.1 (95% CI: 1.2–3.7)]; it was also higher in patients with cancer than in patients without cancer [19.1% vs. 3.6%, risk ratio 3.8 (95% CI 1.6–9.2)]. The risk of dying was highest in the first months subsequent to the VT, after which it gradually approached the mortality rate in the general population. Conclusions: This study provides estimates of incidence and mortality of a first VT event in the general population.

The incidence rate of a first venous thrombosis is 1 to 2 events per 1000 patient-years.^1-3 Venous thrombosis manifests mainly as deep venous thrombosis (DVT) and pulmonary embolism. Environmental risk factors include immobilization, surgery, malignancies, pregnancy, puerperium, and exogenous female hormones.⁴ Genetic abnormalities increasing the risk of a thrombotic event have been known for several decades and include deficiencies of the natural anticoagulants antithrombin, protein C, and protein S. Additional biochemical risk factors for a thrombotic event are factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX, or XI, homocysteine, and fibrinogen.^5-11 Knowledge of the risk of a thrombotic event recurrence and its determinants is relevant for clinical policy regarding screening for thrombophilia, duration of anticoagulant treatment, and prophylactic strategies in circumstances of increased risk.

Summary: Measurement of the thrombin generating potential could provide a method for quantifying the composite effect of multiple risk factors. This study assessed the risk of a first as well as a recurrent venous thrombotic event associated with an increased endogenous thrombin potential (ETP). Analyses were performed in 360 patients and 404 control subjects of the Leiden Thrombophilia Study. The ETP was measured directly using a fluorogenic assay (Thrombinoscope^TM). Individuals with an increased ETP, i.e. above 90th percentile measured in control subjects (>2109·0 nM·min) had a 1·5‐fold [95% confidence interval (CI): 0·9–2·3] increased risk of a first deep venous thrombosis. The risk was more pronounced after the analysis was restricted to idiopathic thromboses, i.e. 1·7‐fold (95% CI: 1·0–2·8). Overall, the hazard ratio of a recurrent thrombotic event associated with a high ETP, adjusted for age, sex and oral anticoagulant use was 1·1 (95% CI: 0·5–2·2). Thus, a high ETP was not associated with an increased relative risk of recurrent venous thrombosis. At present, the clinical relevance of the thrombin generation assay in predicting recurrent venous thrombosis remains uncertain.

Summary Background: The risk of recurrent venous thrombosis is higher in men than in women, and this is so far unexplained. We set out to determine the influence of age, time between first and second event, type of first event, oral contraception, pregnancy and surgery. Methods: We performed a prospective follow-up study of 474 patients with a first objective diagnosis of deep vein thrombosis, aged 18–70 years (Leiden Thrombophilia Study cohort). Results: During 3477 person-years of follow-up, 90 recurrences occurred. The overall incidence rates of recurrence (IRs) were 40.9 per 1000 person-years in men and 15.8 per 1000 person-years in women. Men with an unprovoked first event had the highest risk of recurrence, with almost one-third experiencing a second unprovoked event within 8 years (IR 41.2 per 1000 person-years). This risk was three-fold lower in women [IR 14.2 per 1000 person-years; hazard ratio 2.8 (95% confidence interval 1.4–5.7)]. Age at diagnosis had little effect on recurrence rate, and nor had time elapsed since the first event. In women, almost half of the recurrences were provoked and were mainly related to oral contraceptive use or pregnancy. Conclusions: The higher recurrence rate in men than in women is not the result of differences in the environmental or transient risk factors that we studied. The risk profile for a second thrombotic event is clearly different from that of a first.

Background An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking. The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis. Design and Methods Cases who had a first venous thrombosis (n=515) and matched controls (n=1,505) were identified from a population-based, nested, case-cohort study (the HUNT 2 study) comprising 71% (n=66,140) of the adult residents of Nord-Trøndelag County in Norway. Results The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 (95% confidence interval: 1.2–2.2) compared to subjects with C-reactive protein in the lowest quintile. This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile. Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [odds ratio 1.3 (95% confidence interval: 1.1–1.6)]. Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile. There were no associations between the risk of venous thrombosis and total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, glucose or smoking. We confirmed the positive association between obesity and venous thrombosis. Conclusions C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis. Blood pressure was inversely correlated to venous thrombosis. These findings should be confirmed by further investigations.

In case-control studies, elevated levels of interleukins 6 and 8 have been found to be associated with an increased risk of venous thrombosis (VT). Because of the design of these studies, it remained uncertain whether these alterations were a cause or a result of the VT. In order to distinguish between the two, we set out to measure the levels of six inflammatory markers prior to thrombosis in a population-based cohort using a nested case-cohort design. Between August 1995 and June 1997, blood was collected from 66,140 people in the second Norwegian Health Study of Nord-Trøndelag (HUNT2). We identified venous thrombotic events occurring between entry and 1 January 2002. By this date we had registered 506 cases with a first VT; an age- and sex-stratified random sample of 1,464 controls without previous VT was drawn from the original cohort. Levels of interleukins 1β, 6, 8, 10, 12p70, and tumour necrosis factor-α were measured in the baseline sample that was taken 2 d to 75 mo before the event (median 33 mo). Cut-off points for levels were the 80th, 90th, and 95th percentile in the control group. With odds ratios ranging from 0.9 (95% CI: 0.6–1.5) to 1.1 (95% CI: 0.7–1.8), we did not find evidence for a relationship between VT and an altered inflammatory profile. The results from this population sample show that an altered inflammatory profile is more likely to be a result rather than a cause of VT, although short-term effects of transiently elevated levels cannot be ruled out.