Myocardial Infarction (Progress in reproductive Health Research)

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.

Reference:

http://www.reproline.jhu.edu/english/6read/6issues/6progress/prog46_b.htm