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JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH. 1998 Dec; 52(12):775-85.The World Health Organization (WHO) Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception has quantified the risks of idiopathic venous thromboembolism (VTE), ischemic and hemorrhagic stroke, and acute myocardial infarction (AMI) associated with use of combined oral contraceptives (OCs). The present case-control study estimated the age-specific incidence and mortality of these four diseases among women with no cardiovascular risk factors and modelled the risks attributable to OC use, smoking, and the interaction of the two. Data sources included relative risk estimates from the WHO study and observed incidence rates obtained from hospitals in UK's Oxford region in 1989-93. The increased risk of VTE associated with OC use among nonsmokers contributed over 90% of all cardiovascular events among women 20-24 years and more than 60% in those 40-44 years. Among OC users who smoked, hemorrhagic stroke and AMI accounted for 80% of cardiovascular deaths in the 20-24 year group and 97% among those 40-44 years. Cardiovascular mortality associated with smoking exceeded that associated with OC use at all ages. Attributable risk associated with OC use was 1 death/year/370,000 users aged 20-24 years, 1/170,000 users aged 30-34 years, and 1/37,000 users aged 40-44 years. Among smokers, annual cardiovascular mortality attributable to OC use was estimated at about 1/100,000 users among women under 35 years old and 1/10,000 users among those 35 years of age and older. Among healthy women 35 years and older, the additional mortality associated with OC use is 1.4/100,000/year compared with 5.4/100,000 among smokers and 14/100,000 women who both use OCs and smoke. Any potential reduction in AMI or stroke risk associated with third-generation OCs would be a more important consideration in older women, especially smokers. However, the mortality associated with smoking is far greater than that associated with use of all types of OCs at all ages.