(Stroke. 1996;27:1023-1027.)
© 1996 American Heart Association, Inc.
Articles |
Weekend and Holiday Increase in the Onset of Ischemic Stroke in Young Women
Presented in part at the 6th Nordic Meeting on Cerebrovascular Diseases, Odense, Denmark, September 28-October 1, 1991.
From the Department of Neurology, University of Oulu, and the Department of Neurosurgery (S.J.), University of Helsinki, Finland.
Correspondence to Professor M. Hillbom, MD, Department of Neurology, Oulu University Hospital, 90220 Oulu, Finland.
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Abstract |
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Background and Purpose Chronobiological analyses of stroke onset may throw some light on the mechanisms that trigger stroke. Observations may generate new hypotheses for identifying significant causal relationships.
Methods In the present study, both the circadian and the weekend and holiday versus workday times of the onset of ischemic cerebral infarction were determined for 723 consecutive subjects, aged 16 to 60 years, who were admitted for hospital treatment in the acute phase without any selection.
Results Among young adults (16 to 40 years) and women, more infarctions occurred during weekends and holidays than were expected. Young women in particular had an increased risk for brain infarction during weekends and holidays (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.26 to 3.63). In a multivariate analysis, age of 16 to 30 years (OR, 3.13; 95% CI, 1.57 to 6.50), female sex (OR 1.71; 95% CI, 1.12 to 2.63), and recent drinking of alcohol (P<.01) were associated with the onset of brain infarction during weekends and holidays, whereas current cigarette smoking was associated with the onset of brain infarction during workdays (P<.001). A morning increase in the onset of brain infarction was observed among middle-aged people during both weekends/holidays and workdays. Among young adults, however, an evening increase was also seen during weekends/holidays and workdays.
Conclusions We found that young adults and women are frequently stricken by brain infarction during weekends and holidays and that the circadian distribution of the onset of brain infarction among young adults is different from that of middle-aged people. These observations suggest that there may be stroke-triggering activities that are associated with lifestyle.
Key Words: cerebral infarction • circadian rhythm • lifestyle • young adults
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Recent controlled clinical studies have demonstrated that acute myocardial infarction is frequently triggered by physical activities.1 2 Some other studies have suggested that strenuous physical exercise,3 sexual intercourse,4 5 defecation/micturation,6 and recent heavy alcohol intake7 8 are frequently associated with the onset of aneurysmal subarachnoid hemorrhage. The triggering factors for the other subtypes of stroke remain largely unknown.
It is well known that lifestyle-associated activities, especially among young adults, differ between weekends/holidays and working days. Assuming that typical weekend and holiday activities may include some known or unknown stroke-triggering factors, we investigated the circadian and the weekend/holiday versus workday distributions of the onset of brain infarction separately among young adults and middle-aged people in relation to risk factors of ischemic stroke. We expected that a greater number of strokes would occur on weekends and holidays in young adults compared with middle-aged people and that some lifestyle variables might be associated with the weekend and holiday increase.
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Subjects and Methods |
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The study population consisted of 723 consecutive patients (207 women and 516 men, aged between 16 and 60 years) who were admitted to the Department of Neurology, Helsinki University Hospital, because of first-ever brain infarction between July 1983 and December 1990. The hospital receives patients from its operating district, and practically all patients of working age having an ischemic brain infarction are remitted and admitted without any selection. To exclude cerebral hemorrhage and other cerebral pathologies, head CT scans were performed on 94% of the patients on admission. Head CT scans were performed with equal intensity during weekends/holidays and workdays. The ischemic lesion was not visible in 20% of the CT scans, most probably because of the brain stem location of the lesion or the early timing of the investigation. The rest of the subjects (6%) had clinical signs and symptoms typical of an ischemic attack lasting for more than 24 hours that were verified at neurological examination. Forty-two (6%) of the subjects died later in the hospital.
Data collection and interviews were conducted specifically to investigate the risk-factor profiles for different kinds of ischemic stroke among young adults and people of working age. Data on lifestyle and other risk factors were gathered by interviewing the patients or their relatives and friends within 48 hours after admission and by carefully reviewing the patient charts. All the subjects who were interviewed gave informed consent. The study protocol was approved by the institutional ethical committee of our center.
In the present study, we wanted to find out whether brain infarctions appeared more often on weekdays/holidays than on workdays. The weekend days included Saturdays and Sundays. The holidays included all the Finnish national holidays, such as Independence Day, New Year's Day, Good Friday, May Day, etc. No corrections were made by taking into account occasional sick leaves or vacations. In the tables, we use the word "holiday" to represent both holidays and weekend days as explained above. Assuming that strokes might occur equally often during weekends/holidays and workdays, and taking into account the number of days (832 versus 1909) during the observation period, we calculated odds ratios (ORs) for stroke occurrence on weekends and holidays among young and middle-aged men and women. We also gathered data on the precise time of stroke onset. Such data were available from 610 patients.
We also wanted to establish what kind of lifestyle factors, if any, contributed to the weekend and holiday onset of brain infarction. We had data on hypertension, cardiac disease, diabetes, migraine, hyperlipemia, drinking of alcohol (including recent and previous drinking), smoking status, history of transient ischemic attack, and use of oral contraceptives, as well as the circadian and weekday distributions of stroke onset.
Recent drinking was estimated by asking how many drinks of alcohol (a drink usually contains 12 g ethanol in Finland) the subject had consumed during the 24 hours preceding the onset of the first symptoms of stroke. Data on drinking were available for 74% of the patients. The category of heavy drinkers included the persons whose regular mean weekly alcohol intake had exceeded 300 g ethanol, as well as those who were known to be or have been problem drinkers. Problem drinking was assessed by using the short CAGE questionnaire.9 A score of 1 was given for each positive response to the following four CAGE questions: Have you ever felt you should Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever had a drink first thing in the morning to steady your nerves and to get rid of a hangover (Eye-opener)? Two or more positive answers to these four questions suggest the presence of problem drinking. Both recent and former problem drinkers were included in the category of heavy drinkers.
According to the smoking status, the subjects were categorized into nonsmokers who had never smoked, former (regular) cigarette smokers who had quit at least 1 year ago, and current smokers who smoked 10 and 20 cigarettes per day, with the last cutoff point representing the category of heavy smokers.
Migraine was defined as a typical migrainous headache with or without aura in the patient's earlier history or immediately preceding the onset of brain infarction; thus, the cases of migrainous infarction were included. The patients were considered to be hypertensive if their blood pressure readings before the onset had repeatedly exceeded 160/95 mm Hg or if they were taking antihypertensive medication. Cardiac disease included atrial fibrillation, previously diagnosed myocardial infarction, heart failure, and other cardiac abnormalities that are conventionally considered cardiac sources of emboli. Minor cardiac abnormalities found on echocardiography (such as patent foramen ovale without evidence of paradoxical embolism, mitral valve prolapse, and spontaneous echo contrast) were not included as cardiac diseases leading to cardiogenic embolism. Any diabetes and hyperlipemia had been previously diagnosed, and these patients were either following a diet or taking medication.
The data were collected into a computer database and analyzed
with the biomedical data package statistical programs (BMDP Statistical
Software Inc, University of California at Los Angeles, 1993). The
categorical variables were compared using Fisher's exact
two-tailed test, the Pearson 
2 test, or the
test for linear trend. The OR with 95% confidence intervals (CIs) was
used as an estimate of the relative risk. The univariate
and multivariate ORs were calculated by multiple
logistic regression, which was used to identify the variables
associated with stroke onset on weekends and holidays. The hypothesis
testing and the estimation of the 95% CIs were performed using the
standard error estimate for logistic coefficient estimates.
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Results |
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The baseline characteristics and the risk factors for stroke of all the subjects are shown in Table 1
. We found that
among young adults significantly more infarctions occurred during
holidays than were expected (OR, 1.56; 95% CI, 1.10 to 2.20). The
strokes of young women more frequently occurred on holidays (OR, 2.09;
95% CI, 1.26 to 3.44) than those of young men (OR 1.21; 95% CI, 0.76
to 1.95). The strokes of middle-aged women also showed a tendency
to occur on holidays (OR, 1.18; 95% CI, 0.83 to 1.69), and
consequently all women together had a significant accumulation of
stroke onset on holidays (OR, 1.42; 95% CI, 1.06 to 1.90), whereas the
strokes among middle-aged men were evenly distributed between
holidays and weekdays.
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Analyses of the risk factors revealed that those who were stricken on weekends and holidays had migraine in their past history (including cases of migrainous infarction) significantly more often (P<.05) compared with those stricken on workdays (OR, 1.63; 95% CI, 1.09 to 2.45). However, there was no significant association between the weekend and holiday onsets of ischemic stroke in young women with migraine (OR, 0.68; 95% CI, 0.56 to 2.30). Nor did we find any significant association between the weekend and holiday onset of stroke and the use of oral contraceptives. Of the young women who were stricken on weekends/holidays and workdays, 30% and 39% were current users of oral contraceptives, respectively.
Among the problem and heavy drinkers, the onsets of stroke did not
accumulate on either weekends and holidays or workdays. However, acute
alcohol intake showed associations. The persons with weekend and
holiday strokes were more likely to have consumed alcohol during the
past 24 hours (OR, 2.13; 95% CI, 1.48 to 3.07; P<.001)
(Table 2). This was to be anticipated because the
population data from Finland suggest that 40% of the weekly drinking
occasions occur on Saturdays and Sundays.10 The most
significant association was seen among young men (OR, 4.44; 1.39 to
14.2), whereas among middle-aged women there was neither a negative
nor a positive association (OR, 1.02; 95% CI, 0.41 to 2.58). A more
detailed analysis of the amounts consumed showed that an intake
of more than 40 g ethanol during the preceding 24 hours associated
significantly (P<.01) with weekend and holiday onset among
young (OR, 4.58; 95% CI, 1.57 to 15.7) and middle-aged (2.11; 1.26
to 3.53) men. There was a slight similar tendency among young women
(OR, 2.11; 95% CI, 0.52 to 8.55), but no significant association was
found among middle-aged women (OR, 0.62; 95% CI, 0.15 to 2.53).
The population data from Finland in 1984 suggest that drinking for
intoxication among men counts for 42% of all drinking occasions in the
age group from 15 to 19 years, 35% in the age group from 20 to 29
years, and 26% in the age group from 30 to 49 years, with the
corresponding percentages among women being 22%, 14%, and 8%,
respectively.10
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With stepwise logistic regression, the variables for which the
simultaneous risk of a weekend/holiday onset of
ischemic stroke was tested were sex, age, smoking status,
current smoking, cardiac disease, hypertension, diabetes, hyperlipemia,
history of transient ischemic attack, migraine, and the amount
of recent alcohol consumption and heavy drinking of alcohol.
Univariate and multivariate statistics for
the significant variables are shown in Table 3. The
analysis showed that the significant risk factors for a
weekend/holiday onset of brain infarction were
simultaneously the amount of alcohol consumed within the 24
hours before the onset of the illness, current smoking inversely, sex
(women having a higher risk), and age, with young adults showing the
highest risk. The results were the same after the missing values for
alcohol intake had been added to the analysis as a separate
category.
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Finally, to find some reason why young women in particular were prone
to have ischemic brain infarctions during holidays and
weekends, we analyzed the circadian rhythm of the onset of
stroke in our patient population. The precise circadian time of stroke
onset was available for 610 subjects. There was significant
heterogeneity between time and day of onset of stroke
in young men (P<.01), middle-aged men
(P<.01), and young women (P<.05). It appeared
that young women stricken during weekends and holidays had stroke onset
most frequently around midnight and during the hours before midnight
(Figure), whereas young men showed a peak in the morning
(P<.01). By contrast, among those who were stricken during
workdays, young men showed a peak during afternoon and early evening;
young women showed a circadian distribution similar to that of
middle-aged women. There were significantly fewer
(P=.021) current smokers and heavy drinkers
(P=.030) among the young men who were stricken during
workday afternoons and early evenings (compared with the other young
men). None of the young women stricken during holiday evenings and
nights were heavy smokers, and one was a heavy drinker.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The main finding of the study is that young adults, particularly young women, seem to suffer brain infarctions more often on weekends and holidays than on workdays. Since occasional drinking of alcohol is concentrated on holidays and weekends in Finland,10 it is quite plausible to postulate an association between alcohol drinking and the holiday onset of stroke. However, young men, who were more frequently heavy drinkers than young women, showed a weaker accumulation of stroke onset on holidays than young women. This challenges the hypothesis of heavy drinking being a cause of the peak occurrence of brain infarction on weekends and holidays.11
What makes young women particularly vulnerable to brain infarction during holidays and weekends? We cannot explain the finding by the risk factors tested in the present study. To throw some further light on the association, we analyzed whether the strokes occurring during weekends/holidays and workdays interacted with the circadian system. Several recent reports12 13 14 have demonstrated a morning increase in the onset of ischemic stroke, but young adults have not been studied separately. In the present study, young adults showed different circadian patterns compared with middle-aged persons. In addition to a morning increase during workdays, young women showed a late-evening to night peak during weekends and holidays. In contrast, young men showed a morning increase during weekends and holidays but, surprisingly, also a late-afternoon to early-evening increase during workdays. The previous studies have not revealed these peaks, probably because the data have not been analyzed according to age and sex.
If our observations are not due to chance, there may be some common denominator causing the evening peaks of stroke onset among both young women and men. The occurrence of the weekend and holiday increase suggests that there could be a lifestyle-associated factor triggering the onset of stroke. The fact that young women and men showed different weekday distributions of peak stroke onsets does not necessarily exclude a similar mechanism behind the phenomenon. Because the risk factors showed no associations, we have to speculate what type of risky activities young women engage in during weekends and holidays between 8 PM and 2 AM and what type of risky activities young men pursue during workdays between 2 PM and 8 PM.
Let us assume that strenuous physical exertion is a factor that could trigger the onset of stroke. If a difference in weekday rhythm of activities involving physical exertion exists between women and men, one could anticipate that this would be reflected in the very time of stroke onset. If women have a more sedentary lifestyle during workdays than men, but the activities of men and women are relatively similar during holidays and weekends, this could explain why women show a more obvious peak in the onset of stroke precisely during holidays. In fact, this assumption is supported by the finding that the weekend and holiday increase was not characteristic of only young women but also of middle-aged women.
Although the weekend and holiday increase was clearly linked with female sex, young men also showed a tendency (OR, 1.21) to have more strokes during weekends and holidays. In our previous series,11 15 an equally significant accumulation of the onset of brain infarction on weekends and holidays was seen among young men (OR, 2.03; 95% CI, 1.06 to 3.88; n=49) and women (OR, 1.95; 95% CI, 1.03 to 3.71; n=50), but the data were from the years 1968 to 1979. The marked difference between the young men of the previous and the present series could be due to a change in the weekly rhythm of some lifestyle-associated triggering factor, but we have no proof of this.
Since young adults seem to have some of their strokes during days and hours commonly dedicated to recreational activities, both physical exertion of different kinds and recreational drug use, particularly alcohol drinking, are good candidates as triggering factors. Hilton-Jones and Warlow16 have suggested that nonpenetrating arterial trauma is a very common cause of brain infarction among young adults, and traumas are commonly caused by sports activities and violence associated with alcoholic intoxication.
A good candidate as a triggering mechanism could also be simple transient tachycardia, which may propagate emboli that are already lodging as thrombi in the heart or the large blood vessels. Physical exertion, such as is present during orgasmic sexual intercourse, for example, leads to a rapid heart rate and even to a steep but transient rise in blood pressure.17 Data are lacking to show whether acute alcohol intake modifies blood pressure elevation and heart rate during orgasmic sexual intercourse.18 However, cases of ischemic stroke triggered by orgasmic sexual intercourse have been reported.19 20 21 It is also well known that vomiting, which is a common consequence of alcoholic intoxication and hangover, precipitates a spontaneous Valsalva maneuver leading to a transient right-to-left shunting of blood via a patent foramen ovale. Recently, patent foramen ovale and atrial septal aneurysm were found to be significantly associated with cryptogenic brain infarction.22
The higher incidence of ischemic stroke among young women than young men23 24 25 is an interesting and well-known phenomenon. This does not seem to be due to pregnancy or puerperium because such cases are rare,26 but estrogen-containing oral contraceptives could provide an explanation. These drugs have been found to be associated with an increased thrombotic risk in a dose-dependent way.27 28 A recent study demonstrates that women using oral contraceptives have a lower sensitivity to activated protein C, which means that they run a higher risk for thrombosis.29 The thrombi might be formed while young women lead a sedentary life and are then propagated as emboli when the women undertake strenuous physical activities, which they assumably do not engage in so often during workdays as during holidays. On the other hand, young men are probably more prone to traumatic events. If young men do not lead an equally sedentary life as young women during working days but pursue more sports activities and alcohol drinking during the workday afternoons and evenings compared with young women, this could explain why they show an increase in stroke onset at that time and not at the same time as young women. Further research is needed to prove these hypotheses.
The strengths of our study include the large number of consecutive patients with complete data on the day of stroke onset, the unselected patient material, and the good employment situation in our country during the study period. Despite this, the study also has important limitations. The interpretation of the main finding is hampered by the lack of data on recent alcohol consumption (26%), the hour of stroke onset (15%), and the use of oral contraceptives (13%), for example. Owing to the large number of tests, some of the significant findings may have been due to chance. Finally, factors that are characteristic of the Finnish lifestyle cannot be generalized to apply to all other populations.
Our observations may have some public health implications, although we do not want to emphasize any single factor prematurely. However, recreational drug and heavy alcohol use (particularly binge drinking), as well as the use of oral contraceptives, may need further examination with respect to the risk of stroke. There may be individuals who should avoid heavy alcohol intake or oral contraceptives because they are simply more prone than others to cardiac arrhythmias or thrombus formation.
Received November 2, 1995; revision received February 22, 1996; accepted February 22, 1996.
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