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MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt
Long-term risk of stroke after a first-ever myocardial infarction
Daiva Rastenytė, Diana Šopagienė, Ričardas Radišauskas
Institute of Cardiology, Kaunas University of Medicine, Lithuania
Key words: stroke, myocardial infarction, risk, cumulative risk.
Summary. Purpose. To examine the incidence of stroke during the first three years after
a first-ever myocardial infarction.
Material and methods. Both Kaunas community-based ischemic heart disease register
and stroke register were used as the primary source of data. The methods used for data
collection were those applied by the WHO for the international MONICA project. During
1986 to 1996, 4201 persons aged 25 to 61 years with a first-ever myocardial infarction
were included into Kaunas community-based ischemic heart disease register and followedup for three years against first-ever stroke or death from any cause. Actuarial life tables
were used to analyze risk of stroke.
Results. During the study period, 82 (2.0%) patients with the first-ever stroke that occurred among survivors of myocardial infarction were identified: 68 (82.9%) men and 14
(17.1%) women. The cumulative risk of stroke was 3.19% (95% CI 2.50 to 3.88%) by 3
years: among male myocardial infarction survivors this risk was accounted for 3.37% (95%
CI 2.54 to 4.17%) and that among female – for 2.51% (95% CI 1.22 to 3.80%). The risk
was identified as the highest one early after ictus among the myocardial infarction survivors: 0.43% (95% CI 0.21-0.65%) by 3 months (men – 0.51% (95% CI 0.24 to 0.78%),
women – 0.12% (95% CI 0 to 0.38%)) and 0.23% (95% CI 0.05 to 0.41%) by 6 months
(men – 0.25% (95% CI 0.03 to 0.47%), women – 0.18% (95% CI 0 to 0.53%)).
Conclusion. The risk of stroke is identified as the highest one early after the myocardial
infarction.
Introduction
Heart diseases - acute myocardial infarction (AMI),
disorders of heart rhythm and conduction, endocarditis, heart tumors, diseases of heart valves, etc., are
not the last ones among the main modifiable risk factors of stroke such as arterial hypertension, smoking,
cholesterol, impaired glucose tolerance, diabetes mellitus (DM) (1-3). Stroke is an important complication
of the AMI, occurring in 1% to 3% of all AMI patients
and in 2% to 6% of the patients with anterior wall
infarctions (4). Majority of strokes after AMI is thought
to be embolic, arising from left ventricular wall mural
thrombi, but a number may be atherothrombotic or, in
the acute phase, secondary to hemodynamic compromise. Most strokes occur in the first week after the
infarction, but some risk for stroke remains for an indefinite time (4).
Although morbidity and mortality of major cardiovascular diseases – AMI and stroke are high in comparison with the other European and world countries,
there are only very few studies on relationship be-
tween these two diseases in Lithuania. Therefore, the
aim of the present study was to evaluate the risk of
stroke during the first three years after an index myocardial infarction on the basis of the ischemic heart
disease and stroke registers’ data.
Material and methods
Both Kaunas community-based ischemic heart disease register, which is underway since 1983, and the
community-based stroke register, which is underway
since 1986, and are covering the entire population of
Kaunas city aged 25-64 years, were used as the primary sources of data. The methods used for data collection were those applied by the WHO for the international MONICA (MONItoring of trends and determinants in CArdiovascular disease) project (5) and
were described in detail elsewhere (6-9). The diagnosis of AMI and stroke was based on the criteria proposed by the WHO (5). Diagnostic criteria of AMI or
coronary death were based on: 1) symptoms of a coronary event, 2) ECG findings, 3) serum cardiac enzymes,
Correspondence to D.Šopagienė, Institute of Cardiology, Kaunas University of Medicine, Sukilėlių 17, 3007 Kaunas,
Lithuania. E-mail: [email protected]
Long-term risk of stroke after a first-ever myocardial infarction
4) necropsy findings (6-7). Allocation to the following
epidemiological diagnostic categories was performed:
1 - define AMI; 2 – possible AMI or coronary death;
4 – no AMI or coronary death; 9 – fatal cases with
insufficient data. Stroke was defined as rapidly developed clinical sings of focal or global disturbance of
cerebral function lasting more than 24 hours (except
in cases of sudden death or if the development of symptoms was interrupted by a surgical intervention) with
no apparent cause other than a vascular origin (5, 10).
According to the MONICA protocol, multiple AMI or
stroke attacks occurring within 28 days from the onset of the symptoms of the first attack were considered as one event. The AMI or stroke event was defined fatal if the death occurred within the first 28
days from the onset of AMI or stroke. If the patient
was alive after 28 days from the onset of the attack,
the case was classified as non-fatal.
All records on non-fatal AMI cases recorded among
the persons aged 25-61 years and assigned to the diagnostic categories “1”, “2” or “9” were extracted
from the IHD data-base. All residents of Kaunas city
aged 25-64 years, who experienced their stroke during 1986 to 1999, were included into the stroke register database. Using the patient’ gender and date of
birth as the identification code, and the computed
search system, all new stroke cases that occurred
among the AMI survivors during the first three years
from the onset of AMI, were identified.
Statistical analysis. Actuarial life tables (KaplanMeier method) were used to analyze risk of stroke
(11). Log-Rank test was used to estimate reliability.
Differences in rates at the p< 0.05 level were reported
as statistically significant.
Results
During the 11-year study period (1986 through
1996), 4,201 persons aged 25-61 years experienced
and survived their first-ever AMI: 3368 (80.2%) of
them were men and 833 (19.8%) - women. During
the first three years after the index AMI, 82 (2.0%)
patients had a first-ever stroke: 68 (82.9%) of them
were men and 14 (17.1%) - women. Of all patients,
71 (1.7%) (59 (83.1%) men and 12 (16.9%) women)
had suffered an ischemic stroke.
Frequency of stroke among AMI survivors during
the 3-year follow-up is presented in Table 1. The highest
frequency of stroke was observed among men aged
45-54 years (2.3%) and among women aged 55-61
years (2.4%). Strokes were more prevalent among
male AMI survivors aged 45-54 years than among
MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt
567
females of the same age (2.3% and 0.4%, respectively, p = 0.04). Similar results were obtained looking
at the frequency of ischemic stroke only. However,
there were no statistically significant differences observed between men and women of no one of the age
groups analyzed in respect of the following ischemic
stroke.
The risk of stroke during the 3 years form onset of
AMI is presented in Table 2. Although due to relatively young age of our patients and rather few new
stroke events among them statistical significance has
not been reached, the highest absolute risk of stroke
was during the first 3 months after ictus, 0.43%: 0.51%
among men and 0.12% among women. Among male
AMI survivors, the risk of stroke has decreased twice
(to 0.25%) during the next 3 months (3 to 6 months
time period) and remained rather stable during other
3-month time-periods (Table 2).
Among female AMI survivors, risk of stroke has
decreased a little bit during the second half of the first
year compared to the first 3 months. Compared to the
first year after the index AMI, risk of stroke had an
increasing tendency (Table 2). The risk of stroke was
slightly higher among women than among men during
the third year after AMI (1.49% and 1.13%, respectively). Cumulative risk of stroke by 3 years among
male AMI survivors was 1.3-fold higher compared to
that among female AMI survivors (3.37% and 2.5%,
respectively). The curves of cumulative stroke risk
among male and female AMI survivors have not differed statistically significantly during the 3-year follow-up (Log-Rank = 1.22; p = 0.3) (Figure 1). Similar
results were obtained analyzing the risk of ischemic
stroke among AMI survivors during the first 3 years
of the follow-up (Table 3).
Discussion
The main cause of ischemic heart disease is processes of atherosclerosis in the vessels wall. Because
atherosclerosis is a generalized process that involves
the heart, brain, and peripheral arteries, it is related with
many other clinical manifestations and syndromes. A
substantial proportion of AMI survivors are under the
increased risk of stroke, which leads to a poor clinical
prognosis. According to a number of clinical studies,
during the first 2 weeks ischemic stroke occurs in 15% of AMI patients (12-18). According to the data reported by Kaarisalo M. et al., the risk of stroke was
identified as the highest during the first 2 weeks after
AMI and accounted for 0.7% (19). In our present study,
the risk of stroke among AMI survivors aged 25-61
568
Daiva Rastenytė, Diana Šopagienė, Ričardas Radišauskas
Table 1. Frequency of stroke among the survivors of acute myocardial infarction (AMI) during the
3-year follow-up
Sex
Age
group,
years
AMI
survivors
free of stroke
AMI survivors with of stroke
Total
ischemic stroke hemorrhagic stroke1 all strokes
n (%)
n (%)
n (%)
n (%)
n (%)
Men
25–44
45–54
55–61
25–61
506 (99.2)
1354 (97.7)
1440 (97.8)
3300 (98.0)
4 (0.8)
29 (2.1)
26 (1.8)
59 (1.7)
0
3 (0.2)
6 (0.4)
9 (0.3)
4 (0.8)
32 (2.3)*
32 (2.2)
68 (2.0)
510 (100)
1386 (100)
1472 (100)
3368 (100)
Women
25–44
45–54
55–61
25–61
50 (98.0)
276 (99.6)
493 (97.6)
819 (98.3)
1 (2.0)
1 (0.4)
10 (2.0)
12 (1.5)
0
0
2 (0.4)
2 (0.2)
1 (2.0)
1 (0.4)
12 (2.4)
14 (1.7)
51 (100)
277 (100)
505 (100)
833 (100)
Total
25–44
45–54
55–61
25–61
556 (99.1)
1630 (98.0)
1933 (97.8)
4119 (98.0)
5 (0.9)
30 (1.8)
36 (1.8)
71 (1.7)
0
3 (0.2)
8 (0.4)
11 (0.3)
5 (0.9)
33 (2.0)
44 (2.2)
82 (2.0)
561 (100)
1663 (100)
1977 (100)
4201 (100)
– both intracerebral hemorrhage and subarachnoid hemorrhage included.
*p=0.04 men compared with women.
1
Table 2. Risk of stroke in the survivors of acute myocardial infarction during 3-year follow-up
Sex
Period
less than 3
months
3-6
months
6 - 12
months
12 - 24
months
24 - 36
months
Men
Absolute risk (%)
95 % CI1
Number of stroke patients
Cumulative risk (%)
95 % CI
0.51
0.24–0.78
13
0.51
0.22–0.80
0.25
0.03–0.47
5
0.76
0.41–1.11
0.55
0.22–0.88
11
1.31
0.82–1.80
0.93
0.50–1.36
19
2.24
1.59–2.89
1.13
0.64–1.62
20
3.37
2.54–4.17
Women
Absolute risk (%)
95 % CI
Number of stroke patients
Cumulative risk (%)
95 % CI
0.12
0–0.38
1
0.12
0–0.36
0.18
0–0.53
1
0.30
0–0.71
0.18
0–0.53
1
0.48
0–1.03
0.54
0–1.15
3
1.02
0.2–1.84
1.49
0.46–2.52
8
2.51
1.22–3.80
Total
Absolute risk (%)
95 % CI
Number of stroke patients
Cumulative risk (%)
95 % CI
0.43
0.21–0.65
14
0.43
0.19–0.67
0.23
0.05–0.41
6
0.66
0.37–0.95
0.47
0.20–0.74
12
1.13
0.74–1.52
0.85
0.49–1.21
22
1.98
1.45–2.51
1.21
0.77–1.65
28
3.19
2.50–3.88
1
– 95% CI - 95% confidence interval.
years was the highest one during the first 3 months after ictus (0.43%). As it is reported, after an initial AMI,
strokes and congestive heart failure (CHF) occur at a
rate that is 3 to 6-fold that of the general population
(20). CHF developed in approximately 30% of patients
who had experienced an AMI, which represents a 4 to
6-fold increase in risk. CHF and coronary heart disease may predispose patients to strokes by producing
emboli or decreasing cardiac output and may predispose patients to occur stroke (20).
MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt
Long-term risk of stroke after a first-ever myocardial infarction
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Table 3. Risk of ischemic stroke in the survivors of acute myocardial infarction during 3-year
follow-up
Sex
Period
less than 3
months
3-6
months
6 - 12
months
12 - 24
months
24 - 36
months
Men
Absolute risk (%)
95 % CI1
Number of stroke patients
Cumulative risk (%)
95 % CI
0.33
0.11–0.55
8
0.33
0.09–0.57
0.25
0.03–0.47
5
0.58
0.27–0.89
0.50
0.19–0.81
10
1.08
0.63–1.53
0.94
0.51–1.37
18
2.02
1.41–2.63
0.97
0.52–1.42
18
2.99
2.23–3.75
Women
Absolute risk (%)
95 % CI
Number of stroke patients
Cumulative risk (%)
95 % CI
0.12
0–0.38
1
0.12
0–0.36
0.18
0–0.53
1
0.30
0–0.71
0.18
0–0.53
1
0.48
0–1.03
0.54
0–1.15
3
1.02
0.2–1.84
1.12
0.22–2.02
6
2.14
0.94–3.34
Total
Absolute risk (%)
95 % CI
Number of stroke patients
Cumulative risk (%)
95 % CI
0.29
0.11–0.47
9
0.29
0.09–0.49
0.23
0.05–0.41
6
0.52
0.25–0.79
0.43
0.18–0.68
11
0.95
0.58–1.32
0.85
0.49–1.21
21
1.80
1.29–2.31
1.00
0.6–1.4
24
2.80
2.15–3.45
1
– 95% CI - 95% confidence interval.
Probability of stroke
0,04
Log-Rank=1,22;
p=0,3
Men
0,03
Women
0,02
0,01
0
0
4
8
12
16
20
Months
24
28
32
36
Fig. 1. Cumulative risk of stroke among the acute myocardial infarction survivals aged 25-61
years during 3-year follow-up
The frequency of stroke varies according to the
age of AMI patients, the severity and location of AMI,
and complications, and duration of the follow-up. In
the prethrombolytic era, stroke was associated with a
large anterior AMI and poor left ventricular function.
MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt
It was reported, that about 50% of all post-AMI
strokes were associated with anterior AMI (17, 21),
however, some other studies have not found any association between the occurrence of stroke and site
of AMI (22-23).
570
Daiva Rastenytė, Diana Šopagienė, Ričardas Radišauskas
There are only a few studies on the occurrence of
stroke during a longer follow-up after MI attack. The
annual incidence of stroke is reported between 0.7%
and 3% in different studies (18, 21, 24-28). Cumulative risk of stroke during one year after an index AMI
was 1.13% in our study, which is in accordance with
previous findings; although it was almost twice lower
than compared to Finnish study (2.2%) (19). It should
be noted, however, that our study population was
younger than Finnish one (25-61 yrs vs. 25-74 yrs.).
Arterial fibrillation (AF) may also occur after AMI
as an independent risk factor for post-MI stroke (16).
Also cholesterol reduction with statins has been found
to reduce stroke incidence after AMI (29). As far as
we know, there are no previous studies on whether diabetes mellitus (DM) is a risk factor for post-MI stroke,
although DM is an independent risk factor for thromboembolic stroke (30). Abnormalities of coagulation may
also increase the risk of post-MI stroke (31).
Thrombolysis is more and more often used for AMI
treatment, although thrombolytic therapy is associated
with an increased risk of intracranial hemorrhage that
usually occurs within the first day of therapy. The rate
of post-MI hemorrhagic strokes with thrombolysis is
reported to be 0.3% to 1.1% (13-14, 32-34). The increased risk of hemorrhagic stroke is associated with
advanced age, hypertension, previous stroke, head
trauma, intracranial tumor, arteriovenous malformations and use of tissue plasminogen activator (14, 35).
In our present study, the risk of hemorrhagic stroke
was identified as the highest early after ictus among
male AMI survivors, i.e., during the first 3 months.
Despite the attention focused on the occurrence of
hemorrhagic stroke in the context of thrombolytic
therapy of AMI, nonhemorrhagic stroke remains a
more frequent complication after AMI. There are only
a few community-based studies on the frequency of
ischemic strokes in the thrombolytic era (17, 34). The
frequency of ischemic strokes during hospitalization
has decreased with thrombolytic therapy. Thrombolytic
agents administered soon after AMI might affect the
development of left ventricular thrombus, since early
laminar thrombus, invisible to the echocardiographer,
could have dissolved (17, 34). Another possible explanation for the decreased frequency of ischemic strokes
in AMI patients treated with thrombolysis is that thrombolytic therapy reduces the amount of myocardial damage and, consequently, left ventricular dysfunction
develops less frequently (36).
Conclusion
Among AMI survivors aged 25-61 years the risk
of stroke was identified as the highest one early after
the AMI, i.e., during the first 3 months after ictus.
Galvos smegenų insulto rizika persirgus ūminiu miokardo infarktu
Daiva Rastenytė, Diana Šopagienė, Ričardas Radišauskas
Kauno medicinos universiteto Kardiologijos institutas
Raktažodžai: galvos smegenų insultas, miokardo infarktas, rizika, suminė rizika.
Santrauka. Darbo tikslas – nustatyti galvos smegenų insulto riziką ligoniams, sirgusiems miokardo infarktu.
Darbo apimtis ir metodai. Duomenų šaltiniai – Kauno išeminės širdies ligos bei galvos smegenų insulto
registrai, kaupiantys informaciją apie visus miokardo infarkto bei galvos smegenų insulto atvejus. Analizuojamąją
grupę sudarė 25–61 metų 4201 Kauno gyventojas, kurį 1986–1996 metais ištiko pirmasis miokardo infarktas.
Kiekvienas asmuo, sirgęs miokardo infarktu, stebėtas trejus metus. Tyrimo galinis taškas buvo galvos smegenų
insultas arba mirtis nuo bet kurios priežasties. Galvos smegenų insulto rizika bei suminė galvos smegenų insulto
rizika apskaičiuota remiantis Kaplan-Meier’io išgyvenamumo lentelėmis.
Rezultatai. Tarp 4201 stebėto asmens, sirgusio pirmuoju miokardo infarktu, per trejus metus nuo ligos
pradžios užregistruoti 82 galvos smegenų insulto (visi klinikiniai tipai) atvejai. Trejų metų suminė galvos smegenų
insulto rizika vyrams, sirgusiems miokardo infarktu, buvo 1,3 karto didesnė negu moterims (atitinkamai – 3,37
(95 proc. pasikliautinasis intervalas 2,54–4,17) ir 2,51 proc. (95 proc. pasikliautinasis intervalas 1,22–3,80)).
Didžiausia galvos smegenų insulto rizika po miokardo infarkto buvo nustatyta per pirmuosius tris mėnesius ir
siekė 0,43 proc. (95 proc. pasikliautinasis intervalas 0,21–0,65): vyrams ši rizika siekė 0,51 proc. (95 proc.
pasikliautinasis intervalas 0,24–0,78), moterims – 0,12 proc. (95 proc. pasikliautinasis intervalas 0,0–0,38). Per
MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt
Long-term risk of stroke after a first-ever myocardial infarction
571
kitus 3 mėnesius (3–6 mėn. laikotarpis) vyrams, persirgusiems pirmuoju miokardo infarktu, galvos smegenų
insulto rizika sumažėjo du kartus (atitinkamai nuo 0,51 (95 proc. pasikliautinasis intervalas 0,24–0,78) iki 0,25
proc. (95 proc. pasikliautinasis intervalas 0,03–0,47) ir vėliau ši rizika nekito. Moterims rizika susirgti galvos
smegenų insultu pradėjo mažėti praėjus 6 mėnesiams nuo miokardo infarkto. Lyginant su pirmaisiais metais,
antraisiais ir trečiaisiais metais galvos smegenų insulto rizika po miokardo infarkto moterims toliau didėjo.
Trečiaisiais metais moterų rizika susirgti galvos smegenų insultu buvo kiek didesnė negu vyrų tuo pačiu laikotarpiu
– atitinkamai 1,49 (95 proc. pasikliautinasis intervalas 0,46–2,52) ir 1,13 proc. (95 proc. pasikliautinasis intervalas
0,64–1,62).
Išvada. Galvos smegenų insulto rizika buvo didžiausia ankstyvuoju poinfarktiniu laikotarpiu, nors statistiškai
reikšmingų skirtumų dėl santykinai mažo atvejų skaičiaus nerasta.
Adresas susirašinėjimui: D.Šopagienė, KMU Kardiologijos institutas, Sukilėlių 17, 3007 Kaunas
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Received 15 February 2002, accepted 3 April 2002
MEDICINA (2002) Vol. 38, No. 5 - http://medicina.kmu.lt