Progress in Reproductive Health Research |
Myocardial Infarction
Myocardial infarction, or heart attack, occurs when the blood flow to the heart muscles stops or is reduced sufficiently for long enough to cause cell death. In most cases, myocardial infarction is caused by blockages in coronary arteries by thrombosis.
Myocardial infarction is uncommon in women of reproductive age. Because of this, studies of large populations are needed to determine factors that cause this condition in this population group. Only limited data are available, which show that age, cigarette smoking, diabetes, hypertension and raised total blood cholesterol are important risk factors for myocardial infarction in young women.
Most contraceptive users are healthy with a low incidence of major disease. Thus, even though serious adverse events occur infrequently in contraceptive users, they tend to have greater implications than adverse events arising during the treatment of sick patients. In addition, the very large number of women using steroid hormone contraceptives throughout the world means that even a modest rise in risk has the potential to affect a large number of women.
The first report of coronary thrombosis in an oral contraceptive user was published in 1963. The results of the first epidemiological studies of vascular disease in oral contraceptive users were published in the late 1960s but only two presented data on myocardial infarction and neither found an elevated risk in current users of oral contraceptives. Subsequent studies, however, suggested such risk may be present.
The WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception (1) reported a relative risk of myocardial infarction in current users of combined oral contraceptives of 5.0 in Europe and 4.8 in developing countries. A Transnational Study (2) conducted in 16 centres in six European countries reported a relative risk of myocardial infarction in current users of combined oral contraceptives of 2.4. The Scientific Group concluded that this variation in relative risks reported by the different studies may be due to differences in the prevalence of smoking, especially heavy smoking, and the checking of blood pressure, and to the use of hospital-based rather than community-based controls. The Group found no substantive evidence of increased relative risk of myocardial infarction among previous users of combined oral contraceptives compared with women who have never used them.
A number of studies have tried to determine whether women with established risk factors for myocardial infarction are at especially increased risk if they use combined oral contraceptives. Studies comparing the risk in younger and older users of oral contraceptives found that, while the incidence of myocardial infarction increases with age, there is no convincing evidence that the relative risk of myocardial infarction among current users of oral contraceptives differs with age (1, 3, 4, 5). Research shows that cigarette smoking increases the relative risk of myocardial infarction, irrespective of a woman's use of oral contraception. Studies of current users of combined oral contraceptives who were smokers found substantially higher relative risks among those who were heavy smokers than among those who were light smokers or non-smokers.
In the Transnational Study (2), there was no difference in risk between users of oral contraceptives who did not smoke and non-users who did not smoke. In the WHO study, current users at low risk of cardiovascular disease who did not smoke and who reported having their blood pressure checked before the current episode of use had the same risk of myocardial infarction as non-users who did not smoke. Similar results were found in both developing and European countries.
Two recent studies confirmed that current users of oral contraceptives with a history of high blood pressure have higher relative risks of myocardial infarction than users without such a history (1, 6). In both the WHO and the Transnational Studies, current users of oral contraceptives who reported not having had their blood pressure checked prior to the current episode of use had higher relative risks of myocardial infarction than current users whose blood pressure had been checked.
The amount of increase in blood pressure that increases the risk of myocardial infarction could not be determined in the above case–control studies. Owing to the high background risk of myocardial infarction in women with hypertension, and to the possible enhanced risk of myocardial infarction in such women from the use of combined oral contraceptives, women with known hypertension should be prescribed oral contraception only after careful clinical assessment.
There is little information available about the risk of myocardial infarction in users of oral contraceptives with other recognized risk factors for cardiovascular disease, such as diabetes mellitus, hypercholesterolaemia or a family history of myocardial infarction.
Studies of the influence of the hormonal content of combined oral contraceptives are complicated by the interrelationship between the dose of estrogen and the type and dose of the accompanying progestogen. Early studies suggested a direct relationship between the dose of estrogen and risk of cardiovascular disease. In other studies, conflicting results were found.
An unpublished analysis of data from the WHO study found no increase in the relative risk of myocardial infarction among current users of progestogen-only pills or progestogen-only injectables, compared with non-users of any type of steroid contraceptive. However, more information is needed about the possible risk of myocardial infarction associated with the use of progestogen-only contraceptives.
The Scientific Group concluded that:
The incidence of fatal and non-fatal myocardial infarction is very low in women of reproductive age in both developed and developing countries.
Women who do not smoke, who have their blood pressure checked, and who do not have hypertension or diabetes, are at no increased risk of myocardial infarction if they use combined oral contraceptives, regardless of their age. —There is no increase in the risk of myocardial infarction with increasing duration of use of combined oral contraceptives. There is no increase in the relative risk of myocardial infarction in past users of combined oral contraceptives. These conclusions appear to apply equally to women in developed and developing countries.
Women with hypertension have an increased absolute risk of myocardial infarction. The relative risk of myocardial infarction in current users of combined oral contraceptives with hypertension is at least three times that in current users without hypertension. This conclusion appears to apply equally to women in developed and developing countries.
The increased absolute risk of myocardial infarction in women who smoke is greatly elevated by use of combined oral contraceptives, especially in heavy smokers. This conclusion appears to apply equally to women in developed and developing countries. The relative risk of myocardial infarction in heavy smokers who use combined oral contraceptives may be as high as 10 times that in smokers who do not use combined oral contraceptives.
There are insufficient data about the extent to which use of combined oral contraceptives might modify the risk of myocardial infarction in women with diabetes mellitus, lipid abnormalities or a family history of myocardial infarction.
Although the incidence of myocardial infarction increases exponentially with age, the relative risk of myocardial infarction in current users of combined oral contraceptives does not change with increasing age.
The available data do not allow the effect of the dose of estrogen on the relative risk of myocardial infarction to be evaluated independently of the type and dose of progestogen.
There are insufficient data to assess whether the risk of myocardial infarction in users of low-dose combined oral contraceptives is modified by the type of progestogen. The suggestion that users of low-dose combined oral contraceptives containing gestodene or desogestrel may have a lower risk of myocardial infarction than users of low-dose formulations containing levonorgestrel remains to be substantiated.
References
WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case–control study. Lancet, 1997, 349:1202–1209.
Lewis MA et al. The use of oral contraceptives and the occurrence of acute myocardial infarction in young women. Contraception, 1997, 56:129–140.
Sidney S et al. Myocardial infarction in users of low-dose oral contraceptives. Obstetrics and gynecology, 1996, 88, 939–944.
Mann JI, Inman WHW, Thorogood M. Oral contraceptive use in older women and fatal myocardial infarction. British medical journal, 1976, 2:445–447.
Kreuger DE et al. Fatal myocardial infarction and the role of oral contraceptives. American journal of epidemiology, 1980, 111:655–674.
Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' Oral Contraceptive Study. British medical journal, 1989, 298:165–168.