While combined oral contraceptives are generally considered to be a relatively safe medication, they are contraindicated for people with certain medical conditions. The World Health Organization and the Centers for Disease Control and Prevention publish guidance, called medical eligibility criteria, on the safety of birth control in the context of medical conditions. Estrogen in high doses can increase a person's risk for blood clots. All COCP users have a small increase in the risk of venous thromboembolism compared with non-users; this risk is greatest within the first year of COCP use. Individuals with any pre-existing medical condition that also increases their risk for blood clots have a more significant increase in risk of thrombotic events with COCP use. These conditions include but are not limited to high blood pressure, pre-existing cardiovascular disease (such as valvular heart disease or ischemic heart disease), history of thromboembolism or pulmonary embolism, cerebrovascular accident, and a familial tendency to form blood clots (such as familial factor V Leiden). There are conditions that, when associated with COCP use, increase risk of adverse effects other than thrombosis. For example, people with a history of migraine with aura have an increased risk of stroke when using COCPs, and people who smoke over age 35 and use COCPs are at higher risk of myocardial infarction.