Summary. Background: Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE). Objectives: To conduct a prospective, population-based cohort study to investigate the association between cigarette smoking and the risk of incident VTE. Patients/Methods: Information on smoking habits was assessed by self-administered questionnaires in 24 576 subjects, aged 25-96 years, participating in the fourth Tromsø Study in 1994-1995. Incident cases of VTE were registered until the end of follow-up at 1 September 2007. Results: A total of 389 incident VTE events (1.61 per 1000 person-years) were registered during follow-up (median of 12.5 years). Heavy smokers (> 20 pack-years) had a hazard ratio (HR) of 1.46 (95% confidence interval [CI] 1.04-2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14-2.69) for provoked VTE, as compared with never smokers. The risk of provoked VTE increased with more pack-years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked VTE. The number of pack-years was associated with increased risk of cancer and myocardial infarction, whereas the association between pack-years of smoking and VTE disappeared when failure times were censored at the occurrence of cancer or myocardial infarction. Conclusions: Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking-attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.

Current knowledge of the effect of fish consumption on risk of venous thromboembolism (VTE) is scarce and diverging. Therefore, the purpose of the present study was to investigate the impact of fish consumption and fish oil supplements on the risk of VTE in a population-based cohort. Weekly intake of fish for dinner and intake of fish oil supplements during the previous year were registered in 23,621 persons aged 25-97 y who participated in the Tromsø Study from 1994 to 1995. Incident VTE events were registered throughout follow-up (31 December 2010). Cox-regression models were used to calculate HRs for VTE, adjusted for age, body mass index, sex, triglycerides, HDL cholesterol, physical activity, and education level. During a median of 15.8 y of follow-up there were 536 incident VTE events. High fish consumption was associated with a slightly reduced risk of VTE. Participants who ate fish ≥3 times/wk had 22% lower risk of VTE than those who consumed fish 1-1.9 times/wk (multivariable HR: 0.78; 95% CI: 0.60, 1.01; P = 0.06). The addition of fish oil supplements strengthened the inverse association with risk of VTE. Participants who consumed fish ≥3 times/wk who additionally used fish oil supplements had 48% lower risk than those who consumed fish 1-1.9 times/wk but did not use fish oil supplements (HR: 0.52; 95% CI: 0.34, 0.79; P = 0.002). In conclusion, a high weekly intake (≥3 times/wk) of fish was associated with a slightly reduced risk of VTE, and the addition of fish oil supplements strengthened the inverse effect.

BackgroundPrevious studies have shown differences in the impact of regular physical exercise on the risk of venous thromboembolism. The inconsistent findings may have depended on differences in study design and specific population cohorts (men only, women only and elderly). We conducted a prospective, population-based cohort to investigate the impact of regular physical exercise on the risk of venous thromboembolism. Design and MethodsRisk factors, including self-reported moderate intensity physical exercise during leisure time, were recorded for 26,490 people aged 25-97 years old, who participated in a population health survey, the Tromsø study, in 1994-95. Incident venous thromboembolic events were registered during the follow-up until September 1, 2007. ResultsThere were 460 validated incident venous thromboembolic events (1.61 per 1000 person-years) during a median of 12.5 years of follow-up. Age, body mass index, the proportion of daily smokers, total cholesterol, and serum triglycerides decreased (P<0.001), whereas high density cholesterol increased (P<0.001) across categories of more physical exercise. Regular physical exercise of moderate to high intensity during leisure time did not significantly affect the risk of venous thromboembolism in the general population. However, compared to inactivity, high amounts of physical exercise (≥3 hours/week) tended to increase the risk of provoked venous thromboembolism (multivariable hazard ratio, 1.30; 95% confidence interval, 0.84-2.0), and total venous thromboembolism in the elderly (multivariable hazard ratio, 1.33; 95% confidence interval, 0.80-2.21) and in the obese (multivariable hazard ratio, 1.49; 95% confidence interval, 0.63-3.50). Contrariwise, compared to inactivity, moderate physical activity (1.0-2.9 hours/week) was associated with a border-line significant decreased risk of venous thromboembolism among subjects under 60 years old (multivariable hazard ratio, 0.72; 95% confidence interval, 0.48-1.08) and subjects with a body mass index of less than 25 kg/m 2 (multivariable hazard ratio, 0.59; 95% confidence interval, 0.35-1.01). ConclusionsOur study showed that regular, moderate intensity physical exercise did not have a significant impact on the risk of venous thromboembolism in a general population. Future studies are required to assess the impact of regular physical exercise on venous thromboembolism risk in different population subgroups.Key words: venous thromboembolism, physical exercise, general population.Citation: Borch KH, Hansen-Krone I, Braekkan SK, Mathiesen EB, Njolstad I, Wilsgaard T, and Hansen J-B. Physical activity and risk of venous thromboembolism. The Tromsø study. Haematologica 2010;95(12):2088-2094. doi:10.3324/haematol.2009 © F e r r a t a S t o r t i F o u n d a t i o n

Word count abstract: 250Total word count: 4970The authors report no potential conflict of interest SummaryModerate alcohol consumption has been shown to protect against cardiovascular diseases.The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption were collected by a self-administrated questionnaire in 26 662 subjects, aged 25-97 years, who participated in the Tromsø Study, in 1994-95. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE.However, subjects consuming ≥3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, BMI, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI:1.00-2.33). Contrary, subjects with a wine intake of ≥3 u/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (≥1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.

Word count abstract: 250Total word count: 4970The authors report no potential conflict of interest SummaryModerate alcohol consumption has been shown to protect against cardiovascular diseases.The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption were collected by a self-administrated questionnaire in 26 662 subjects, aged 25-97 years, who participated in the Tromsø Study, in 1994-95. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE.However, subjects consuming ≥3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, BMI, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI:1.00-2.33). Contrary, subjects with a wine intake of ≥3 u/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (≥1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.