Incidence of Stroke and Myocardial Infarction in Women of Reproductive Age
Background and Purpose Information on the incidence of vascular disease in women of reproductive age has been limited. These diseases are rare in this age group, and a large population base is required for reliable estimation of incidence.
Methods For a case-control study of vascular disease and low-dose oral contraceptive use, we used emergency department logs and hospital admission and discharge records to ascertain fatal and nonfatal cases of first-ever stroke and myocardial infarction (MI) in women 15 to 44 years of age who were members of a large California HMO. Incidence rates of stroke and MI were calculated on the basis of these data.
Results The incidence of MI not associated with pregnancy was 5.0 per 100 000 women-years. The incidence of stroke not associated with pregnancy was 10.7 per 100 000 women-years. MI was very rare until age 35 years. At every age, about half of hemorrhagic strokes were due to subarachnoid hemorrhage.
Conclusions The incidence rates of stroke and MI are low in women of reproductive age in the United States.
Information on the incidence of vascular disease in women of reproductive age has been limited. Vascular disease in young women is rare, and a very large population base is required for reliable estimation of incidence. We recently completed a case-control study examining the relative risk of stroke and myocardial infarction (MI) in users of low-dose oral contraceptives.1 2 The study was done in the defined population of members of a large HMO in California. We report the incidence derived from our study of first-ever MI and stroke in women 15 to 44 years of age.
Subjects and Methods
The study was done in the defined population of members of the Kaiser Permanente Medical Care Program, Southern and Northern California Regions. It was approved by the Kaiser Permanente Institutional Review Boards for the Protection of Human Subjects of both northern and southern California.
Emergency department logs, admission and discharge records, and records of out-of-plan billings were reviewed to identify cases of stroke or MI in women aged 15 to 44 years. The period of care ascertainment was May 1, 1991, through August 31, 1994, in northern California and July 15, 1991, through August 31, 1994, in southern California.
To identify cases, women who had a diagnosis of stroke or MI or who were admitted to the hospital or emergency department for conditions that might indicate a diagnosis of stroke or MI (eg, headache, chest pain, loss of consciousness) were identified by screening the information sources described above. Next, project nurses reviewed the clinical records of possible cases and excluded women who had a prior history of stroke or MI. The project nurses screened out women whose clinical presentation was clearly incompatible with a diagnosis of stroke or MI. The records of remaining possible cases were reviewed by project investigators and verified as cases of stroke or MI using predefined criteria.
Diagnostic criteria for MI were adapted from those of the American Heart Association Council on Epidemiology.3 Included as MI cases are events categorized as definite or probable MI on the basis of chest pain (presence or absence), cardiac enzymes, and electrocardiographic findings.
Stroke was defined as the new onset of rapidly developing symptoms and signs of loss of cerebral function that lasted at least 24 hours and had no apparent cause other than that of vascular origin. Specifically excluded were neurological events due to subdural hematoma, brain tumor, infection, metabolic derangement, and multiple sclerosis. To verify the stroke diagnosis, records of all potentially eligible cases were reviewed by two physicians (D.B.P. and S.S.) who considered clinical signs and symptoms and the results of tests and procedures. Discrepancies in their assessment were adjudicated by a project neurologist. In addition to clinical presentation, the results of CT and MRI scans, lumbar puncture, angiography, autopsy, and surgery were used in case reviews. Stroke cases were subclassified as being venous, hemorrhagic, or ischemic infarction or other and unknown. Hemorrhagic strokes were further subclassified as intraparenchymal, subarachnoid, or mixed/uncertain using the same method of case review and using the results of CT and MRI scans, surgery, and autopsy. All but two stroke cases that were not immediately fatal had a CT or MRI scan.
Incidence rates per 100 000 women-years were calculated using yearly third-quarter membership counts as denominators. Rates were calculated after excluding subjects who were pregnant at the time of their vascular event. Calculation of 95% confidence limits was based on the assumption that the case counts have a Poisson distribution and using the relationship between the Poisson and χ2 distributions.4
The period of case ascertainment encompassed 3.6 million women-years of observation. There were 184 definite and probable cases of first-ever MI and 397 confirmed first-ever stroke cases. After excluding cases during pregnancy, the incidence of MI was 5.0 per 100 000 women-years, and the incidence of stroke was 10.7 per 100 000 women-years (Table 1⇓). The incidence of both stroke and MI increased with age, but the rate of increase with age was steeper for MI. MI was very rare until 35 years of age.
The overall incidence rates of ischemic and hemorrhagic stroke were almost exactly the same, about 5 per 100 000 women-years (Table 2⇓). The incidence of hemorrhagic stroke was about the same as the incidence of ischemic stroke from ages 15 to 29 years and higher than for ischemic stroke from ages 30 to 39. The pattern then reversed. For ages 20 to 39 years, about half of hemorrhagic strokes were due to subarachnoid hemorrhage. For 76 of 107 of the subarachnoid hemorrhages (71.0%), there was confirmation of an aneurysm. Nine of 87 hemorrhagic strokes that were not subarachnoid (10.3%) had a documented aneurysm.
Three MI cases, which were not included in the calculation of MI incidence, occurred during a pregnancy. Eleven stroke cases, which were not included in the calculation of stroke incidence, occurred during a pregnancy. There were about 195 000 deliveries to Kaiser Permanente members during the period of case ascertainment. On the basis of these data, the risk of MI was 1.5 per 100 000 deliveries. The risk of stroke was 5.6 per 100 000 deliveries.
Table 3⇓ summarizes the results of population-based studies in which information on the incidence of first-ever stroke in women younger than 35 years was presented.5 6 7 8 9 10 11 12 13 The number of cases of first-ever stroke in these studies was small. Our study adds to the body of literature on stroke incidence in this age group because the number of stroke cases was large in comparison with previous studies. Our study confirms the rarity of stroke in women aged 15 through 35 years, a conclusion that is consistent with other published data. The information about stroke incidence in women in this age group helps put in perspective any increases in the risk of stroke that might be associated with oral contraceptive use.
The MONICA project has provided information about the incidence of first-ever stroke in women 35 to 44 years of age from 18 different stroke registers that used common methods for identifying and classifying stroke cases. The incidence of stroke in women aged 35 to 44 years in our study population was 20.6 per 100 000. The Figure⇓ summarizes the information about stroke incidence in women aged 35 to 44 years presented by Thorvaldsen et al14 in a 1995 publication about the MONICA study results. Estimates of stroke incidence in this age group in MONICA sites varied by a factor of 7, ranging from 8 per 100 000 in Moscow, Russia, to 55 per 100 000 in Kuopio, Finland. Because the distribution of factors associated with the risk of stroke (hypertension, diabetes, alcohol use, cigarette smoking, and body mass index) probably differs by country, the geographic variation in stroke incidence is not surprising.
The ratio of hemorrhagic to ischemic stroke was 1:1 in our study population. This ratio varied by age. Only the study of Kittner et al5 presented data on the incidence of hemorrhagic and ischemic stroke separately. Subarachnoid hemorrhage was excluded, and the data are not comparable with ours. Kittner et al5 found a strong relationship between ethnicity and stroke incidence. The relationship varied according to stroke type. Compared with whites, blacks had a twofold higher risk of ischemic stroke and a threefold higher risk of hemorrhagic stroke. In our study, the relationship of several other important risk factors for stroke differed according to stroke type.1 An increase in body mass index was associated with an essentially linear increase in the risk of ischemic stroke. The relationship of body mass index with hemorrhagic stroke was more complex. The lowest risk was observed in women in the second quartile of body mass index, and there was no increase in risk for women in the highest compared with the lowest quartile of body mass index. In diabetic subjects, the relative risk of ischemic stroke was 7.15, whereas the relative risk of hemorrhagic stroke in diabetics was only 2.50. Because risk of various subtypes of stroke differs for different factors, the ratio of ischemic to hemorrhagic stroke would not be expected to be constant across populations. The membership of Kaiser Permanente in northern and southern California is broadly representative of California in terms of ethnicity. In women in this age group, about 54% are white non-Hispanic, 20% Hispanic, 12% African American, 10% Asian, and 4% other and unknown.
Published information on the incidence of MI in women of reproductive age could not be found. We found that MI in women younger than 45 years is rare and MI in those younger than 35 years is extremely rare.
Our study has limitations. Fatal events occurring without transfer to a hospital or emergency department would not have been ascertained by our surveillance system. We attempted to assess the degree of underreporting of cases due to death at home by using information from computer linkage between our membership files and California death certificates for the years 1992 and 1993. We could not use death certificates to identify cases in this study because the lag between death occurrence and the availability of this information is long. We estimate that we missed no more than 10% of stroke cases because we did not identify fatal cases not transferred to a hospital or emergency department. The limitation due to exclusion of some fatal events should be recognized when interpreting our data.
Reprint requests to Dr Petitti, Research and Evaluation, SCPMG, 393 E Walnut St, Pasadena, CA 91188. E-mail email@example.com.
- Received September 4, 1996.
- Revision received October 25, 1996.
- Accepted October 25, 1996.
- Copyright © 1997 by American Heart Association
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