Annals of Internal Medicine
A Community-Based Study of Stroke Incidence after
Myocardial Infarction
Brandi J. Witt, MD; Robert D. Brown Jr., MD, MPH; Steven J. Jacobsen, MD, PhD; Susan A. Weston, MS; Barbara P. Yawn, MD; and
Véronique L. Roger, MD, MPH
Background: The rate of stroke after myocardial infarction (MI)
remains unclear.
Objectives: To examine the rate of stroke after incident MI;
compare it with that observed in the population of Rochester,
Minnesota; determine how the rate of stroke after MI has changed
over time; and examine the impact of stroke on survival after
incident MI.
Design: Community-based cohort.
Setting: Olmsted County, Minnesota.
Participants: Persons with incident (first-ever) MI between 1979
and 1998.
Measurements: Ischemic or hemorrhagic stroke in hospitalized
and nonhospitalized patients that was identified by screening of
the medical record for stroke diagnostic codes and subsequent
stroke confirmation by physician review of the recorded event.
Medical record review was used to ascertain baseline characteris-
tics and death.
Results: A total of 2160 persons with incident MI were hospi-
talized between 1979 and 1998 and followed for a median of 5.6
C oronary disease is the leading cause of death in the
United States, and stroke is the third leading cause of
death and the most common cause of disability (1). Both
diseases share common risk factors (2–7) and treatments,
such as antihypertensive agents, lipid-lowering agents, and
aspirin (8, 9). Because the incidence of myocardial infarc-
tion (MI) is stabilizing and survival after MI is improving
(10, 11), understanding the burden of morbidity after MI
and how it may be changing over time becomes increas-
ingly important in caring for the growing population of
survivors. Several investigators, including our group, have
reported declining recurrence of MI and heart failure after
incident MI (10, 12–16). However, less is known about
stroke after MI. Most studies that have reported rates of
stroke after MI focused on short-term events that occurred
during the patient’s hospital stay or within the first month
after MI. They often addressed the question within the
framework of clinical trials, which may not be fully repre-
sentative of the experience of the community. Finally, the
reported rate of stroke early after MI is difficult to interpret
because of the lack of an appropriate reference population.
This study was done to address these gaps in knowl-
edge by examining, in a geographically defined population,
the rate of stroke after MI over a comprehensive period of
observation. We included data not only from the first
month after MI but also for several years afterward, within
a rigorously characterized longitudinal MI incidence co-
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Article
years (range, 0 to 22.2 years). The rate of stroke was 22.6 per
1000 person-months (95% CI, 16.3 to 30.6 per 1000 person-
months) during the first 30 days after MI, corresponding to a
44-fold increase (standardized morbidity ratio, 44 [95% CI, 32 to
59]) risk for stroke in the population of Rochester, Minnesota. The
risk for stroke remained 2 to 3 times higher than expected during
the first 3 years after MI. Older age, previous stroke, and diabetes
increased the risk for stroke, which did not decline over the study
period. Strokes were associated with a large increase in the risk for
death after MI (hazard ratio, 2.89 [CI, 2.44 to 3.43]).
Limitations: Findings may not be generalizable to different pop-
ulations. The authors measured outcomes by reviewing medical
records.
Conclusions: In the community, the risk for stroke is markedly
increased after MI, particularly early after MI, compared with the
expected risk in population without MI. Stroke is associated with
a large increase in the risk for death after MI.
Ann Intern Med. 2005;143:785-792. www.annals.org
For author affiliations, see end of text.
hort spanning 2 decades. Specifically, we evaluated the ex-
cess risk for stroke that MI confers compared with that in
the general population, the secular trends in the occurrence
of stroke after MI, factors predictive of stroke after MI, and
the impact of stroke on survival post-MI.
METHODS
Study Setting
This study was conducted in Olmsted County, Min-
nesota, where residents receive medical care at a small
number of facilities, including the Mayo Clinic. The char-
acteristics of the study population mainly reflected those of
U.S. white persons. The Rochester Epidemiology Project
(17), a medical record linkage system, enables access to all
aspects of an individual patient’s records from all sites in
Olmsted County. These comprehensive medical records
See also:
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Summary for Patients. . . . . . . . . . . . . . . . . . . . . . . I-36
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6 December 2005 Annals of Internal Medicine Volume 143 • Number 11 785
 Article Community Study of Stroke after Myocardial Infarction
Context
After a myocardial infarction (MI), outcomes such as heart
failure and recurrent MI are decreasing. What about
stroke?
Contribution
This cohort study from Olmsted County, Minnesota, had a
44-fold increase in stroke rate during the first month after
MI compared with the stroke rate in the general commu-
nity. Stroke rates in the cohort declined markedly after the
first month but exceeded the rates in the general commu-
nity for 3 years. Strokes after MI were associated with in-
creased risk for death, and their rate did not decline be-
tween 1979 and 1998.
Implications
Early after MI, risk for stroke is markedly increased. This
risk has not declined over time.
—The Editors
allow the study of diseases over a prolonged period as they
occur in an unselected, geographically defined population
without many of the biases inherent in tertiary care set-
tings. The appropriate institutional review boards ap-
proved all aspects of the study.
Identification of the Study Cohort
The procedures used to assemble the MI incidence
cohort have been described previously (11). Briefly, all per-
sons discharged from county hospitals between 1979 and
1998 with codes compatible with an MI were identified.
The following target codes were included from the Inter-
national Classification of Diseases, Ninth Revision, Clini-
cal Modification (ICD-9-CM): 410 (acute MI), 411 (other
acute and subacute forms of ischemic heart disease), 412
(old MI), 413 (angina pectoris), and 414 (other forms of
ischemic heart disease). All events coded 410 and samples
of events coded 411 through 414 were reviewed (11).
Trained abstractors verified patients’ residency status in
Olmsted County and incident status of MI by complete
review of the medical record and collected information on
the presence of cardiac pain, creatine kinase values, and
electrocardiograms, which were assigned a Minnesota
Code by the Electrocardiogram Reading Center at the
University of Minnesota (18). Standard criteria were ap-
plied to assign the diagnosis of MI on the basis of cardiac
pain, enzyme values, and Minnesota Code. Comorbidity
was measured by the Charlson index, a validated measure
of comorbidity (19). Reperfusion therapy was defined as
thrombolysis or percutaneous coronary intervention that
was done during the hospitalization. Atrial fibrillation was
recorded at any time during the patients’ medical histories
before the stroke occurred.
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In the Rochester Stroke Registry (20), all residents of
Rochester, Minnesota, who had stroke diagnoses identified
through the Rochester Epidemiology Project are validated
by physician review and entered in the Registry. The ICD-
9-CM codes used for case ascertainment include codes 430
through 438 (cerebrovascular disease), 781.4 (transient pa-
ralysis of a limb), 784.3 (aphasia), 362.34 (transient arte-
rial occlusion, amaurosis fugax), and 368.12 (transient vi-
sual loss). Because the MI incidence cohort includes all of
Olmsted County and the Stroke Registry includes only
residents of the city of Rochester, there is incomplete over-
lap between the 2 registries. Thus, all strokes occurring
before July 2003 in residents of Olmsted County that were
not included in the Stroke Registry were identified by us-
ing the same aforementioned diagnostic codes and were
validated by physician review.
Stroke Definitions
To avoid temporal changes in the ascertainment of
stroke related to changes in imaging techniques and to be
certain of the timing of stroke, strokes without a corre-
sponding clinical event that were found only on imaging of
the patient’s head (computed tomography [CT] or mag-
netic resonance imaging [MRI]) or at autopsy were not
included. Transient ischemic attacks defined as focal neu-
rologic symptoms lasting less than 24 hours; traumatic
subdural hematoma; hemorrhage into abnormal tissue,
such as tumor or inflammation; and isolated infarction of
the retina, labyrinth, or cochlea were excluded.
Cerebral infarction was defined as the acute onset
(minutes to hours) of a focal neurologic deficit persisting
more than 24 hours, with or without CT or MRI docu-
mentation, and caused by altered circulation to a limited
region of the cerebral hemispheres, brainstem, or cerebel-
lum. Findings on CT, MRI, or autopsy (if available) did
not show evidence of intracerebral hemorrhage.
Intracerebral hemorrhage was defined as the acute on-
set of a focal neurologic deficit associated with some or all
of the following: headache, vomiting, altered level of con-
sciousness, signs of meningeal irritation, or blood-stained
cerebrospinal fluid. If done, CT, MRI, or autopsy showed
a parenchymal hemorrhage.
Subarachnoid hemorrhage was defined as the abrupt
onset of headache, with or without altered consciousness,
with signs of meningeal irritation. A focal deficit may have
developed acutely or with a delay of hours or days. Com-
puted tomography, MRI, or examinations of cerebrospinal
fluid examinations showed blood in the subarachnoid
space.
Strokes were classified as “hospitalized strokes” if a
hospital admission for stroke or stroke-related complica-
tions occurred within 30 days after the event. Follow-up
was obtained by passive surveillance through community
(inpatient and outpatient) medical records. More than
90% of the population of Olmsted County receives ongo-
ing care at Mayo Clinic or Olmsted Medical Center, and
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96% of residents are seen, on average, every 3 years at
Mayo Clinic (17). Ascertainment of death included death
certificates filed in Olmsted County, autopsy reports, obit-
uary notices, and electronic files of death certificates ob-
tained from the State of Minnesota Department of Vital
and Health Statistics.
Quality Control
The reliability of MI ascertainment has been reported
previously (11) and indicates excellent interabstractor
agreement. For stroke ascertainment, the study neurologist,
in addition to the principal investigator, reviewed a sample
of 25 randomly selected potential cases, of which 16 were
ischemic strokes, 1 was a hemorrhagic stroke, and 8 were
nonstrokes. The interobserver variability showed excellent
agreement (␬ ⫽ 0.93; 95% CI, 0.79 to 1.00) between the
2 physicians, indicating excellent reliability for the ascer-
tainment of stroke. Furthermore, previous work from our
center indicated that the case-finding approach used in the
current study yielded results similar to those reported for a
cohort approach confirming the robustness of our method
of ascertainment (20).
Statistical Analysis
The rate of stroke after MI was examined for all
strokes (first and recurrent) and for incident (first-ever)
strokes and was expressed per 1000 person-months. The
incident stroke rate after MI was compared with the inci-
dent stroke rate in the population of Rochester, Minne-
sota, by using data from the Rochester Stroke Registry (21)
to calculate standardized morbidity ratios. Expected stroke
rates were calculated by applying sex-, age-, and period-
specific stroke rates in the general population of Rochester
to the person-time follow-up of the study population. The
standardized morbidity ratio was calculated by dividing the
number of observed strokes by the expected number of
strokes over the duration of follow-up. Confidence inter-
vals were calculated according to the Poisson distribution.
Proportional hazards regression was used to examine
associations between patient characteristics and the occur-
rence of a stroke after MI and to examine the association
between stroke and death after MI while adjusting for age,
sex, Killip class, aspirin use, and warfarin use; stroke was
analyzed as a time-dependent covariate. The correlation of
the scaled Schoenfeld residuals with time was used to test
the proportional hazards assumption. Except for family
history of coronary artery disease (7.2%), anterior MI
(15.8%), ST-segment elevation MI (12.8%), and presence
of Q waves (21%), missing values did not exceed 5%.
Because ST-segment elevation and presence of Q waves are
both surrogates for MI severity, we elected to use peak
creatine kinase ratio, defined as the ratio of the maximum
creatine kinase value to the upper limit of normal, as the
measure of MI severity. The peak creatine kinase ratio was
missing in less than 5% of the observations. Fewer than
2% of persons had 1 or more missing variables for the
predictors in the final multivariable models. Because the
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Community Study of Stroke after Myocardial Infarction Article
proportional hazards assumption was not met, strokes were
divided into early strokes (occurring ⱕ 30 days after MI)
and late strokes (occurring ⬎ 30 days after MI). For late
strokes, the proportional hazards assumption was met for
all predictor variables (P ⬎ 0.05 for all variables). Results
are reported as hazard ratios with 95% CIs. Analyses were
done using the statistical software package SAS, version 8.2
(SAS Institute Inc., Cary, North Carolina).
Role of the Funding Source
The funding source supported the data collection, data
analysis, and manuscript preparation.
RESULTS
Baseline Characteristics
Between 1979 and 1998, 2171 Olmsted County resi-
dents were hospitalized with incident MI. Stroke could not
be ascertained as an outcome in 11 patients, resulting in a
cohort of 2160 persons. The mean age (SD) at the date of
index MI was 67 years (SD, 14), and 57% of the patients
were men. Fifty-six percent of the patients had a history of
hypertension, and 65% were current or former smokers.
One hundred eighty-eight (9%) had a stroke before the
index MI. Nearly all strokes that occurred before the MI
were ischemic (174 [93%]), and the remaining 7% con-
sisted of 7 intracerebral hemorrhages and 7 subarachnoid
hemorrhages.
Occurrence of Stroke after MI
During a median follow-up of 5.6 years (range, 0 to
22.2 years), there were 273 strokes, of which 259 (95%)
were ischemic; the remaining 5% consisted of 13 intra-
cerebral hemorrhages and 1 subarachnoid hemorrhage.
Eighty-three percent of the patients were hospitalized for
evaluation within 30 days of the stroke. The occurrence of
stroke was not equally distributed during the follow-up
period; a large proportion of the strokes (18%) occurred
within 30 days of the index MI followed by a gradual
decline thereafter.
Table 1 shows the rates per 1000 person-months for
all strokes (first and recurrent) and for incident (first-ever)
strokes for the duration of follow-up. The rate was the
highest during the first 30 days after MI, at 23.9 per 1000
person-months (CI, 17.6 to 31.6 per 1000 person-months)
for all strokes, equating to 2.3% of all patients with MI.
When only incident strokes after MI were considered, the
observed rate of incident strokes during the first 30 days
was 22.6 per 1000 person-months (CI, 16.3 to 30.6 per
1000 person-months). Compared with the expected rate,
this represents a 44-fold increase in the risk for stroke
(standardized morbidity ratio, 44 [CI, 32 to 59]).
In the second month of follow-up, the stroke rate de-
clined to 2.3 per 1000 person-months without additional
change during the remainder of the first year. The risk for
stroke declined gradually as time from the index MI in-
creased but remained 2 to 3 times higher than the expected
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 Article Community Study of Stroke after Myocardial Infarction

Table 1. Rate of Stroke after Myocardial Infarction in Olmsted County, Minnesota*

Time after MI All Strokes† Incident Strokes†

Attack Rate/1000 person-months Incidence Rate/1000 person-months SMR

(95% CI) (95% CI) (95% CI)
0–30 d 23.9 (17.6–31.6) 22.6 (16.3–30.6) 44 (32–59)
31 d–1 y 1.9 (1.3–2.6) 1.6 (1.0–2.3) 3.1 (2.0–4.5)
1–2 y 1.6 (1.0–2.2) 1.3 (0.8–1.9) 2.4 (1.5–3.7)
2–3 y 1.2 (0.7–1.9) 1.2 (0.7–1.8) 2.2 (1.3–3.4)
3–4 y 0.9 (0.5–1.5) 0.9 (0.5–1.5) 1.6 (0.9–2.8)
4–5 y 0.9 (0.5–1.6) 0.9 (0.5–1.6) 1.6 (0.8–2.8)

* MI ⫽ myocardial infarction; SMR ⫽ standardized morbidity ratio.

† All strokes and attack rate refer to first and recurrent events, whereas incident and incidence refer to first-ever strokes.

rate during the 3 years after MI. Beyond year 3, the risk for
stroke was no longer different from that in the general
population of Rochester. The dynamic nature of the excess
risk for stroke after MI is shown in the Figure, which
depicts the gradual decline over time of the observed versus
expected strokes (standardized morbidity ratio) from the
time of the index MI throughout the follow-up.
The risk for stroke after MI did not decline in patients
with more recent MIs. During the first decade of the study,
after adjustment for age and sex, the risk for stroke in-
creased by 74% (hazard ratio for stroke after an MI occur-
ring in 1988 compared with that after an MI occurring in
1979, 1.74 [CI, 1.12 to 2.71]; P ⫽ 0.015). During the
second decade, no additional change in the risk for stroke
after MI was detected (hazard ratio for stroke after an MI
occurring in 1998 compared with that after an MI occur-
ring in 1988, 0.87 [CI, 0.54 to 1.41]; P ⫽ 0.57). The
results were unchanged after adding previous stroke, hyper-
tension, diabetes, smoking, hyperlipidemia, and obesity to
the model.
Characteristics Associated with Stroke after Incident MI
Older age, female sex, greater comorbidity, hyperten-
sion, diabetes, atrial fibrillation, Killip class, and previous
Figure. Ratio of observed strokes in the myocardial infarction
(MI) cohort to expected strokes in Rochester, Minnesota
(standardized morbidity ratio [SMR]).
50
40
10
SMR
stroke were all univariately associated with stroke after MI
(Table 2). No association was seen between stroke and
peak creatine kinase ratio, location of MI, presence of Q
waves, or ST-segment elevation. Regarding thrombolysis,
there was no clinically significant difference between pa-
tients who had a stroke and those who did not, although
patients who had a stroke were less likely to receive percu-
taneous coronary intervention.
When entered in a multivariable model, the factors
independently associated with stroke after MI included
older age (hazard ratio, 1.04 per year [CI, 1.03 to 1.05 per
year]; P ⬍ 0.001); history of stroke (hazard ratio, 2.07 [CI,
1.44 to 2.97]; P ⬍ 0.001); and diabetes mellitus (hazard
ratio, 1.68 [CI, 1.27 to 2.20]; P ⬍ 0.001). Adjusting for
the use of aspirin, ␤-blockers, angiotensin-converting
enzyme inhibitors, statins, calcium-channel blockers, or
diuretics at admission or at discharge did not change the
results, nor did we detect an interaction between hyperten-
sion and any of these medications (data not shown). Be-
cause of the markedly higher excess risk for stroke early
after MI, exploratory analyses were conducted to examine
whether the association between any clinical variable and
stroke differed by the timing of the stroke. Persons who
had a stroke early after MI were older than those who had
a stroke later (P ⬍ 0.001) and had a larger MI as measured
by peak creatine kinase ratio (P ⫽ 0.030).
Survival after Stroke
At 1 year, follow-up was 99% complete and 402 pa-
tients had died. Patients who had a stroke at any time
during follow-up had a markedly increased risk for death
compared with patients who did not have a stroke (Table
3). Indeed, stroke was associated with a 2- to 3-fold in-
crease in the risk for death, independent of age, sex, and
Killip class. Similar results were found after adjusting for

aspirin and warfarin use.

5

3
DISCUSSION
Patients with MI have a high risk for strokes, most of
1
0
which are ischemic. The risk for stroke after MI is dynamic
1 2 3 4 5 and declines as time from the index MI increases. How-
Years after MI ever, the risk for stroke after MI did not decline during the
2 decades of the study period. The excess risk for stroke
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 Community Study of Stroke after Myocardial Infarction Article

after MI is considerable compared with that expected in a
population without MI, particularly in the first month af-
ter MI. The devastating impact of stroke after MI on sur-
vival and the increasing number of persons at risk because
of improved survival constitute an important public health
matter for persons with coronary disease.
Risk for Stroke after MI
Most studies considered strokes during the initial hos-
pital admission for the MI or the first month thereafter and
reported rates ranging between 0.75% and 4.6% (2, 4, 6,7,
22–34). However, most of these are clinical trials that are
not comparable with our study. Among cohort studies,
stroke rates ranged from 1.1% to 1.5% in the first 30 days
after MI (4, 35, 36). Several methodologic issues limit the
inferences that can be made from these studies. These is-
sues include, in particular, the exclusion of elderly individ-
uals, the lack of long-term follow-up, reliance of the study
design on registries from trials or national surveys, and
small sample size.
Data on long-term risk for stroke after MI are also
sparse. Stroke rates range from 3% at 6 months to 8.6% at
10 years after MI (22, 37– 46). As is the case for studies
reporting short-term stroke rates, many of these are clinical
trials. Cohort studies providing long-term data are limited
because they identified survivors through administrative
databases (39) or through billing records (43). Also, they
did not provide information on the background stroke
rates in a similar population, except for 1 report from the
Monitoring of Cardiovascular Disease (MONICA) study,
where the rate of stroke within 28 days after MI was mark-
edly higher than that expected in the general study popu-
lation (4). This study, however, did not include older per-
sons. Thus, our data extend these findings by including
participants of all ages and providing a comparison popu-
lation, which is essential to understand the magnitude of
the excess risk for stroke conferred by MI. Finally, tempo-
ral trends in the risk for stroke after MI remain largely
unknown with the exception of data from the Worcester

Table 2. Characteristics of Patients with Myocardial Infarction by Occurrence of Stroke*

Characteristics MI without Stroke MI with Stroke RR for Characteristic P Value

(n ⴝ 1887) (n ⴝ 273) if Stroke Occurs
(95% CI)
Men, % 58 46 0.48 (0.38–0.61) ⬍0.001

Mean age at index MI (SD), y 67 (14) 71 (12) 1.05 (1.04–1.06) ⬍0.001

Comorbid conditions, % ⬍0.001

0 44 33 1
1 or 2 36 47 2.30 (1.75–3.02)
ⱖ3 21 20 2.88 (2.03–4.07)

Cardiovascular risk factors

Hypertension, % 54 64 1.93 (1.50–2.47) ⬍0.001
Diabetes mellitus, % 19 27 2.03 (1.55–2.66) ⬍0.001
Current smoker, % 30 25 0.55 (0.42–0.73) ⬍0.001
Hyperlipidemia, % 33 28 0.81 (0.62–1.05) 0.114
Mean BMI (SD), kg/m2 27.0 (5.6) 26.8 (4.9) 0.98 (0.96–1.01) 0.22
Familial coronary disease, % 21 23 0.92 (0.68–1.23) 0.56

Clinical characteristics at index MI

Previous stroke, % 8 14 3.20 (2.25–4.55) ⬍0.001
Killip class 2, 3, or 4, % 35 35 1.50 (1.16–1.93) 0.002
Atrial fibrillation, % 12 14 1.58 (1.11–2.24) 0.011
Anterior location of the MI, % 35 34 1.11 (0.85–1.46) 0.45
STEMI, % 40 39 0.91 (0.70–1.19) 0.50
Q-wave MI, % 50 48 1.02 (0.79–1.34) 0.87
Peak CK ratio, % 0.95
Tertile 1 31 28 1
Tertile 2 32 33 1.03 (0.76–1.40)
Tertile 3 33 36 1.06 (0.78–1.43)
Reperfusion therapy, %
PCI 28 22 0.68 (0.51–0.90) 0.008
Thrombolysis 15 15 0.86 (0.62–1.21) 0.39
Aspirin† 67 65 1.12 (0.86–1.45) 0.41
Warfarin† 10 15 1.70 (1.22–2.36) 0.002
LMWH† 37 39 0.90 (0.70–1.15) 0.40
Antiplatelet‡ 23 24 0.88 (0.66–1.16) 0.36
Calcium-channel blocker† 40 49 1.20 (0.94–1.53) 0.14
Diuretics† 54 62 1.82 (1.42–2.33) ⬍0.001

* BMI ⫽ body mass index; CK ⫽ creatine kinase; LMWH ⫽ low-molecular-weight heparin; MI ⫽ myocardial infarction; PCI ⫽ percutaneous coronary intervention; RR ⫽
relative risk; STEMI ⫽ ST-segment elevation myocardial infarction.
† Includes use in-hospital and at discharge.
‡ Includes ticlopidine and clopidogrel use in-hospital and at discharge.
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 Article Community Study of Stroke after Myocardial Infarction
Table 3. Risk for Death after Myocardial Infarction Associated with Stroke*
Risk for Death Unadjusted RR P Value
for Death
(95% CI)
All stroke 3.94 (3.32–4.67) ⬍0.001
Early stroke† 3.15 (2.27–4.37) ⬍0.001
Late stroke‡ 4.03 (3.33–4.89) ⬍0.001
* RR ⫽ relative risk.
† Strokes occurring ⱕ 30 days after myocardial infarction.
‡ Strokes occurring ⬎ 30 days after myocardial infarction.
Heart Attack Study, which suggested an increase in the risk
for in-hospital stroke with time but lacked information
about long-term follow-up (35).
As a result of these limitations, the magnitude and the
dynamic nature of the risk for stroke after MI have not
previously been recognized. Our study addresses this im-
portant gap in knowledge by showing that, within this
geographically defined population, using rigorous defini-
tions for MI and stroke and including strokes in patients
who were not hospitalized, the observed rate of incident
stroke after MI is high, largely exceeding that expected in a
population without MI. Also, the risk for stroke after MI is
dynamic and is markedly elevated early after MI. Indeed,
compared with the expected incidence of stroke, the excess
risk observed within 30 days after MI corresponds to a
44-fold increased risk for stroke. During the 2 decades of
the study, no reduction in this risk was detected; however,
an increase was apparent during the first decade with sta-
bilization thereafter. These data suggest that contemporary
management strategies for MI have not affected the subse-
quent risk for stroke compared with older therapies.
Predictors of Stroke after MI
Factors independently associated with an increased
risk for stroke included older age, history of stroke, and
diabetes, all of which are traditionally associated with
stroke in the general population. However, the timing of
stroke in relation to MI suggests that conventional cardio-
vascular risk factors do not fully explain the marked in-
crease in the risk for stroke early after MI. Regarding acute
treatment of MI, meta-analyses of the randomized trials of
thrombolysis in acute MI eased the concern that throm-
bolysis increased the risk for stroke considerably (47, 48).
Our study extends these reports by indicating that the rate
of hemorrhagic stroke after MI in the community is low.
Also, the stabilization of the rate of stroke in the second
decade of the study, corresponding to the “thrombolytic
era,” suggests that the use of thrombolytics, which in-
creased over that period (49), did not coincide with an
increase in hemorrhagic stroke.
The association between the size and severity of the
MI and stroke remains controversial. Some authors suggest
that severity is related to stroke (3, 4, 7, 25), whereas oth-
ers failed to detect such an association. Our analyses sug-
gest that larger size is associated with early occurrence of
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RR for Death Adjusted P Value RR for Death Adjusted for P Value
for Age and Sex Age, Sex, and Killip Class
(95% CI) (95% CI)
2.85 (2.40–3.38) ⬍0.001 2.89 (2.44–3.43) ⬍0.001
2.22 (1.60–3.09) ⬍0.001 2.27 (1.63–3.15) ⬍0.001
2.95 (2.43–3.58) ⬍0.001 2.99 (2.46–3.62) ⬍0.001
stroke after MI. Finally, the timing of the stroke in relation
to the MI suggests that systemic inflammation, which plays
an increasingly recognized role in MI and stroke, may
partly explain the marked increase in the risk for stroke
during the early period after MI (50).
Implications
These results have important implications. Our find-
ings contrast with trends in cardiac outcomes after MI,
such as heart failure (12) and recurrent MI (16, 51–53),
which are declining over time. Stroke conversely exhibits
no temporal decline, and therefore our data constitute
proof of concept that the current therapies for acute MI do
not confer adequate protection against stroke, particularly
in the early phase after MI. The use of oral anticoagulation
after acute MI remains controversial, despite increasing ev-
idence that suggests a potential benefit in stroke prevention
(48, 54, 55), because of the concern that the risk for bleed-
ing associated with warfarin use outweighs its benefit. Not-
withstanding this valid concern, our data suggest that the
use of antithrombotic measures relying on different agents
should be revisited. Our documentation of the dynamic
nature of the risk for stroke after MI can further assist in
determining the appropriate duration of such therapies.
The strong association between stroke and death further
underscores the need to aggressively pursue preventive ap-
proaches.
Several synergistic factors contribute to the increase in
the absolute number of strokes after MI, including the
increase in the number of MI survivors and the increased
prevalence of 2 chief characteristics associated with stroke,
namely older age and diabetes mellitus. These factors,
along with the increased awareness of the importance of
morbidity after MI in the growing and aging population of
survivors of MI (56), indicate that increased attention
should be dedicated to devising more effective stroke pre-
vention strategies.
Limitations
The risk for stroke has increased in black and Hispanic
persons (57). Although the population of Olmsted County
is becoming more diverse, the population during the study
period consisted primarily of U.S. white persons. Thus,
these findings should be reexamined in different racial and
ethnic groups. We do not have information on the distri-
www.annals.org

bution of follow-up visits after MI and could only match
the comparison population on the risk factors of age, sex,
and year of diagnosis. Thus, we could not determine the
proportion of the excess risk for stroke associated with MI
that might be explained by traditional risk factors or MI
alone. The observational design of our study did not allow
us to determine whether anticoagulant or antiplatelet med-
ications were prescribed to treat or to prevent stroke after
MI, limiting our ability to draw conclusions regarding the
use of such medications and stroke risk. Although subtyp-
ing of ischemic strokes in our cohort is not available, its
impact on analysis would probably be minimal; many early
strokes would have been classified as cardioembolic, be-
cause of their temporal association to the MI (58).
Conclusions
These data from a geographically defined population
indicate that patients with MI have a high risk for stroke,
which is not declining as treatment for MI improves. The
excess risk for stroke after MI compared with that expected
in a population without MI is considerable, particularly in
the early phase. It is also dynamic and declines as time
from the index MI increases. The devastating impact of
stroke on survival and the increased number of patients at
risk because of improved survival after MI constitute an
important public health matter for persons with coronary
disease.
From Mayo Clinic and Olmsted Medical Center, Rochester, Minnesota.
Acknowledgments: The authors thank Ryan A. Meverden, BS, and Jill
Killian, BS, for assistance with statistical analyses, and Kristie Shorter for
secretarial support.
Grant Support: In part by grants AR30582, HL59205, and HL68765
from the Public Health Service, National Institutes of Health.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Véronique L. Roger, MD, MPH, Divi-
sion of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW,
Rochester, MN 55905.
Current author addresses and author contributions are available at www
.annals.org.
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www.annals.org
 Annals of Internal Medicine
Current Author Addresses: Drs. Witt, Brown, Jacobsen, and Roger and
Ms. Weston: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Dr. Yawn: Olmsted Medical Center, 210 Ninth Street SE, Rochester,
MN 55904.
Author Contributions: Conception and design: B.J. Witt, R.D. Brown,
S.J. Jacobsen, B.P. Yawn, V.L. Roger.
Analysis and interpretation of the data: B.J. Witt, R.D. Brown, S.J.
W-160 6 December 2005 Annals of Internal Medicine Volume 143 • Number 11
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Jacobsen, S.A. Weston, V.L. Roger.
Drafting of the article: B.J. Witt, S.J. Jacobsen.
Critical revision of the article for important intellectual content:
B.J. Witt, R.D. Brown, S.A. Weston, B.P. Yawn, V.L. Roger.
Final approval of the article: B.J. Witt, R.D. Brown, B.P. Yawn.
Statistical expertise: S.A. Weston.
Obtaining of funding: V.L. Roger.
Collection and assembly of data: B.J. Witt.
www.annals.org