title: Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use.
abstract: The results of studies investigating the relationship of smoking with venous thrombosis are inconsistent. Therefore, in the MEGA study, a large population-based case-control study, we evaluated smoking as a risk factor for venous thrombosis and the joint effect with oral contraceptive use and the factor V Leiden mutation. Consecutive patients with a first venous thrombosis were included from six anticoagulation clinics. Partners of patients were asked to participate and additional controls were recruited using a random digit dialing method. Participants completed a standardized questionnaire. Individuals with known malignancies were excluded from the analyses, leaving a total of 3,989 patients and 4,900 controls. Current and former smoking resulted in a moderately increased risk of venous thrombosis (odds ratio (OR)(current) 1.43, 95% confidence interval (CI95) 1.28-1.60, OR(former) 1.23, CI95 1.09-1.38) compared with nonsmoking. Adjustment for fibrinogen levels did not substantially change these risk estimates. A high number of pack-years resulted in the highest risk among young current smokers (OR(>or=20 pack-years) 4.30, CI95 2.59-7.14) compared with young nonsmokers. Women who were current smokers and used oral contraceptives had an 8.8-fold higher risk (OR 8.79, CI95 5.73-13.49) than nonsmoking women who did not use oral contraceptives. Relative to nonsmoking noncarriers, the joint effect of factor V Leiden and current smoking led to a 5.0-fold increased risk; for the prothrombin 20210A mutation this was a 6.0-fold increased risk. In conclusion, smoking appears to be a risk factor for venous thrombosis with the greatest relative effect among young women using oral contraceptives.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Pomp
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Carine J M
authors.initials: CJ
authors.lastname: Doggen
mesh_terms: D000328:Adult; D000368:Aged; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000235:genetics
chemical_list: D003276:Contraceptives, Oral