Association of Exercise-Induced, Silent ST-Segment
Depression With the Risk of Stroke and Cardiovascular
Diseases in Men
S. Kurl, MD; J.A. Laukkanen, MD; T.-P. Tuomainen, MD; R. Rauramaa, MD, PhD, MSc;
T.A. Lakka, MD, PhD; R. Salonen, MD, PhD; J. Eränen, MD;
J. Sivenius, MD, PhD; J.T. Salonen, MD, PhD, MScPH
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Background and Purpose—There are few if any data on the prognostic importance of silent myocardial ischemia during
exercise with regard to the risk of stroke and cardiovascular diseases (CVDs) among asymptomatic men. In this
prospective study, we investigated the relation of silent myocardial ischemia and the risk of stroke and CVD death in
men with and without conventional risk factors.
Methods—The study sample included 1726 middle-aged men with no history of stroke, coronary heart disease, or atrial
fibrillation at baseline. Silent myocardial ischemia was defined as a horizontal or downsloping ST-segment depression
(ⱸ1 mm) during exercise electrocardiography. A total of 86 CVD-related deaths and 78 strokes occurred during an
average follow-up of 10 years.
Results—Men with silent ischemia during exercise had a 3.5-fold increased risk of CVD death and a 2.2-fold increased
risk of stroke compared with men without silent ischemia, after adjusting for conventional risk factors. Silent ischemia
during exercise was associated with a 3.8-fold (95% confidence interval [CI], 1.5 to 9.5) increased risk for CVD in
smokers, a 3.9-fold (95% CI, 2.1 to 7.3) increased risk in hypercholesterolemic subjects, a 3.6-fold (95% CI, 1.9 to 6.8)
increased risk in the hypertensives, and 3.8-fold (95% CI, 2.0 to 7.1) increased risk in overweight men. The respective
relative risks for stroke were 3.8 (95% CI, 1.1 to 12.5), 3.5 (95% CI, 1.7 to 7.4), 3.4 (95% CI, 1.6 to 7.1), and 2.9 (95%
CI, 1.4 to 6.1).
Conclusions—Exercise-induced silent myocardial ischemia is an important indicator of increased risk of stroke and CVD
in men with other risk factors, such as smoking, hypercholesterolemia, hypertension, and being overweight. (Stroke.
2003;34:1760-1765.)
Key Words: cardiovascular diseases 䡲 risk factors 䡲 silent ischemia 䡲 stroke, cardioembolic
is commonly used to screen both men ⬎45 and women ⬎55
years of age with suspected CHD. Ischemic ST-segment
changes during exercise are considered a marker of myocardial ischemia due to underlying coronary atherosclerosis. It is
also possible that myocardial ischemic ST-segment changes
may indicate an increased risk of other CVDs because of
generalized atherosclerosis. Furthermore, ischemic STsegment changes in the presence of common risk factors
such as hypertension, smoking, hypercholesterolemia, and
overweight may increase the probability of CHD, as well
as other atherosclerotic CVDs. However, there are no
previous population-based studies exploring whether silent, exercise-induced, ST-segment depression predicts the
risk of CVDs and cerebrovascular diseases in high-risk
individuals.
P
revious studies have shown that exercise-induced myocardial ischemia increases the risk of future coronary
events in both patients with coronary heart disease (CHD)1– 6
and asymptomatic individuals with no prior CHD.7 There are,
however, few if any data demonstrating that silent ischemia
during or after exercise has a long-term prognostic significance with regard to stroke and cardiovascular disease (CVD)
death.7,8 The likelihood of detecting myocardial ischemia is
known to be higher among those with an increased pretest
probability of CHD, such as asymptomatic, high-risk individuals.9,10 Little is known about the prognostic value of
exercise-induced silent myocardial ischemia in high- and
low-risk individuals, however.
Some evidence shows that electrocardiographic (ECG)
findings may predict the risk of stroke.11,12 The exercise test
Received June 18, 2002; final revision received March 4, 2003; accepted March 5, 2003.
From the Research Institute of Public Health (S.K., J.A.L., T.-P.T., T.A.L., R.S., J.E., J.T.S.), Kuopio; the Kuopio Research Institute of Exercise
Medicine (J.A.L., R.R., T.A.L.), Kuopio; the Inner Savo Health Centre (J.T.S.), Suonenjoki; and the Departments of Clinical Physiology and Nuclear
Medicine (R.R.) and of Neurology (J.S.), Brain Research and Rehabilitation Centre Neuron, Kuopio University Hospital, University of Kuopio, Kuopio,
Finland.
Reprint requests to Prof Jukka T. Salonen, Research Institute of Public Health, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. E-mail
[email protected]
© 2003 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000078564.46376.0A
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Kurl et al
Silent Ischemia and Stroke and Cardiovascular Risk
The aim of the present study was to investigate the
prognostic significance of silent myocardial ischemia during
an exercise test with regard to the risk of any CVD death and
stroke in a population-based sample of asymptomatic men.
Additionally, we investigated whether hypertension, overweight, serum LDL cholesterol level, and smoking modify
these associations in men with no prior stroke or CHD.
Methods
Subjects
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Subjects were participants in the Kuopio Ischemic Heart Disease
Risk Factor Study, an ongoing, population-based study designed to
investigate risk factors for CVD, atherosclerosis, and related outcomes in men from eastern Finland, an area of high coronary
morbidity and mortality.13 Each subject gave written, informed
consent. The Research Ethics Committee of the University of
Kuopio approved the Kuopio Ischemic Heart Disease Risk Factor
Study. The baseline examinations were conducted between March
1984 and December 1989. The subjects were a random sample of
men aged 42, 48, 54, or 60 years at the baseline examination. Of
3235 eligible men, 2682 (82.9%) participated in the study.
Men who had prevalent, clinically diagnosed CHD (n⫽888),
stroke (n⫽69), or atrial fibrillation (AF; n⫽26) and for whom an
exercise stress test was not performed because of severe CVD or
some other disease (n⫽25) at baseline were excluded from the study.
Some of these men may have had 2 or more of these diseases (CHD,
stroke, or AF). There were 37 men with CHD and stroke, 9 had CHD
and AF, and 11 had stroke and AF at the same time. Prevalent CHD
was defined as either a history of myocardial infarction or typical
angina pectoris,14 the use of nitroglycerin for chest pain once a week
or more frequently, or chest pain as a cause for stopping the exercise
test. Thus, the present study is based on 1726 men who had complete
data on ECG recordings during exercise.
Exercise Tolerance Test
A maximal, symptom-limited, exercise stress test was performed
with an electrically braked bicycle ergometer between 8 AM and 12
noon. The testing protocol comprised a 3-minute warm-up at 50 W
followed by a step-by-step increase in the workload by 20 W/min
(Tunturi EL 400 bicycle ergometer) for 407 (23%) men. The
remaining 1362 men (77%) were tested with a linear increase in the
workload of 20 W/min (Medical Fitness Equipment 400 L bicycle
ergometer). Maximal oxygen uptake was measured directly with a
respiratory gas analyzer, as explained previously.15 Also, heart rate
and blood pressure were registered during the exercise test. Blunted
heart rate response was defined as inability to achieve 85% of the
age-predicted, maximal heart rate during exercise.
The most common reasons for stopping the exercise test early
were exhaustion (1235 men), breathlessness (229 men), and pain in
the leg, joints, or back (n⫽69). The test was discontinued because of
cardiorespiratory symptoms or abnormalities for 120 men. These
included arrhythmias (n⫽51), a marked change in systolic (SBP) or
diastolic blood pressure (n⫽35), dizziness (n⫽8), or ischemic ECG
changes (n⫽6). Exercise-induced, ventricular conduction disorders
were observed in 4 men, 1 of whom also had silent myocardial
ischemia during exercise.
Assessment of Exercise-Induced
Myocardial Ischemia
The ECG was recorded continuously with a Kone 620 ECG. The
Mason-Likar lead system, including Vl, V5, and aVF lead connections, was used.16 The ECG was printed out at 30-second intervals
during exercise and for at least 5 minutes of recovery while the
subject was sitting on the bicycle. Exercise ECGs were coded
manually by 1 cardiologist (J.E.).
Silent myocardial ischemia during exercise and afterward was
defined as ischemia in the ECG without typical chest pain indicating
CHD. The criteria for ischemia on the ECG during exercise were
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horizontal or downsloping ST-segment depressions ⱸ1.0 mm at 80
ms after the J-point or any ST-segment depression ⬎1.0 mm at 80
ms after the J-point.
Ascertainment of Strokes and CVD Death
Incident strokes between 1984 and 1992 were ascertained through
the FINMONICA stroke register.17 Information on stroke incidence
between 1993 and December 31, 1998 was obtained by computerized linkage to the Finnish national hospital discharge registry and
death certificate registry. Diagnostic information was collected from
hospitals and classified by 1 neurologist (J.S.) using diagnostic
criteria identical to the FINMONICA criteria. The sources of
information on stroke were from hospital documents, death certificates, autopsy reports, and medicolegal reports. The diagnosis of
stroke was based on the sudden onset of clinical signs or focal or
global disturbance of cerebral function lasting ⬎24 hours (except in
the case of sudden death or when interrupted by surgical intervention) with no apparent cause other than a vascular origin. Each
suspected stroke (ICD-9 codes 430 to 439 and ICD-10 codes I60-I68
and G45-G46) was classified as (1) definite stroke, (2) no stroke, or
(3) an unclassifiable event. The data from the FINMONICA stroke
register were annually rechecked with the data obtained from the
computerized national hospital discharge and death registers. Definite strokes and unclassifiable events were included in the group of
any stroke. Each definite stroke was classified as (1) an ischemic
stroke (ICD-9 codes 433 to 434 or ICD-10 code I63) or (2) a
hemorrhagic stroke (ICD-9 codes 430 to 431 or ICD-10 codes
I60-I61). If the subject had multiple nonfatal strokes during followup, the first stroke was considered the end point. The average
follow-up time was 10.4 years (range, 0.3 to 13.4 years). A total of
78 first strokes occurred, of which 59 were ischemic strokes. In the
present sample, there were 86 CVD deaths (ICD-9 and ICD-10 codes
390 to 459 and I00-I99, respectively), 60 of which were due to CHD
and 19 due to stroke.
Assessment of Other Risk Factors
The examination protocol and the assessment of medical history, use
of medications, smoking habit, alcohol consumption, blood pressure,
and body mass index (BMI) have been described in detail previously.15,18,19 Hypertension was defined as SBP ⬎140 mm Hg, diastolic
blood pressure ⬎90 mm Hg, or the use of antihypertensive medication. BMI was computed as the ratio of weight in kilograms divided
by the square of height in meters. The collection of blood specimens
and the measurement of serum lipids have been presented previously
elsewhere.18,19
Statistical Methods
Differences in baseline characteristics between men with and without
silent myocardial ischemia during exercise were analyzed by Student’s t test. The associations of silent myocardial ischemia during
exercise with the risk of stroke and CVD death were analyzed by risk
factor–adjusted, forced Cox proportional-hazards models. Wherever
possible, confounding factors were entered uncategorized into the
Cox models. Relative hazards, adjusted for age, examination years
(1985,1986, 1987, 1988, and 1989) and the well-known risk factors
(smoking habit, alcohol consumption, SBP, BMI, diabetes, and
serum LDL cholesterol) for CVDs and stroke were estimated as
antilogarithms of coefficients for independent variables.
The modification of risk factors was analyzed by comparing the
prognostic value of silent myocardial ischemia among (1) smokers
and nonsmokers, (2) men with higher (ⱸ3.5 mmol/L) and lower
(⬍3.5 mmol/L) serum LDL cholesterol levels, (3) hypertensive and
normotensive men, and (4) overweight to obese (ⱸ25 kg/m2) men
and normal-weight (⬍25 kg/m2) men. Statistical tests for significance were 2-sided, and analyses were performed with SPSS, version
10.0, for Windows.
Results
Baseline Characteristics
Baseline characteristics in men with and without myocardial
ischemia during exercise are shown in Table 1. Serum LDL
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July 2003
TABLE 1.
Baseline Characteristics of the Study Population
Men With No Myocardial Men With Myocardial
Ischemia During
Ischemia During
Exercise (n⫽1603),
Exercise (n⫽123),
Mean (SD)
Mean (SD)
P
Value
Age, y
52.2 (5.3)
52.7 (5.3)
0.27
Body mass index, kg/m2
26.8 (3.4)
26.1 (3.1)
0.11
30.4
23.0
0.08
Smokers, %
Cigarette smoking, pack-years
7.95 (16.0)
4.78 (12.8)
0.04
Alcohol consumption, g/wk
74.4 (117.6)
68.8 (94.0)
0.60
3.9
4.1
0.94
3.99 (0.99)
4.18 (0.96)
0.04
0.85
Diabetes, %
Serum LDL cholesterol, mmol/L
Serum HDL cholesterol, mmol/L
1.31 (0.30)
1.31 (0.27)
Systolic blood pressure, mm Hg
133.6 (16.0)
137.2 (18.0)
0.02
Diastolic blood pressure, mm Hg
88.9 (10.3)
90.0 (10.4)
0.93
Family history of CHD (t test), %
46.3
51.5
0.422
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Resting HR, beats/min
62 (11)
62 (10)
0.83
Maximal HR, beats/min
160 (20)
167 (17)
⬍0.001
Inability to achieve 85% target HR
16.0%
7.7%
0.02
Maximal oxygen uptake, mL/kg/min
31.9 (7.5)
32.5 (7.5)
0.39
33 114
35 342
⬍0.001
Maximal rate-pressure product,
beats 䡠 mm Hg
LDL denotes low-density lipoprotein; HDL, high-density lipoprotein; HR, heart rate.
cholesterol, resting SBP, maximal heart rate, and ratepressure product were higher in men with silent myocardial
ischemia during exercise. The number of cigarettes smoked
was lower in men with silent ischemia. There were no
significant differences in other baseline characteristics between men with and without silent ischemia during exercise.
Prevalence of Silent Myocardial Ischemia
at Baseline
In this study sample, there were 123 (7.1%) men with silent
ischemia during exercise. Silent ischemia during exercise was
observed in 5.4% (n⫽28) of smokers, in 8.3% (n⫽89) of
hypercholesterolemic men, in 7.7% (n⫽68) of hypertensive
men, and in 6.0% (n⫽69) of overweight men. The number of
men with reasons other than silent ischemia for having an
abnormal exercise test were 78 (including severe arrhythmias,
no increase in SBP, and painful ischemia).
Number of Strokes and CVD Deaths
During Follow-Up
Seventeen (13.8%, P⬍0.05) of 123 men with silent ischemia
during exercise and 69 (4.3%, P⬍0.05) of 1603 men without
silent ischemia died of CVD during follow-up. The respective
numbers (percentages) for stroke were 10 (8.1%) and 68
(4.2%). A total of 9 men had both an acute coronary event and
a stroke, of whom 2 had the acute coronary event before
stroke during the follow-up.
Strongest CVD Risk Factors
The strongest risk factors for stroke were elevated SBP
(P⬍0.001) and silent ischemic ST-segment depression during
exercise (P⫽0.02). The strongest risk factors for CVD death
were smoking (P⬍0.001), elevated SBP (P⬍0.001), silent
ischemic ST-segment depression during exercise (P⬍0.001),
and alcohol consumption (P⫽0.02). In these multivariate
models, blunted heart rate response and maximal oxygen
uptake were not related to the risk of stroke, whereas the later
was inversely related to the risk of CVD death (P⫽0.03).
Relative Risk of Stroke and CVD Death in Men
With Silent Myocardial Ischemia
Men with silent ischemia during exercise had a 2.2-fold increased
risk of stroke and a 3.5-fold increased risk of CVD death compared
with men without silent ischemia, after adjusting for conventional
risk factors (Table 2). Silent ischemia after exercise was associated
with a 5.2-fold increased risk of CVD death but was not associated
with the risk of stroke. The cumulative hazard curves for CVD
death and stroke continued to diverge during the follow-up period
(Figures 1 and 2). Also, milder silent ischemia (defined as a
horizontal or downsloping ST-segment depression of 0.5 to
0.9 mm) during exercise was related to an increased risk of CVD
death (relative risk [RR]⫽3.0; 95% confidence interval [CI], 1.5 to
6.0, P⫽0.001).
Interactions of Silent Ischemia With Conventional
CVD Risk Factors
Silent ischemia during exercise had a stronger association
with the risk of CVD death and stroke in smokers and in
hypercholesterolemic, hypertensive, and overweight men
than in men without such risk factors (Figure 3a and 3b).
Silent ischemia during exercise had a strong association with
the increased risk of CVD death in smokers (RR⫽3.8; 95%
CI, 1.5 to 9.5), in hypercholesterolemic men (RR⫽3.9; 95%
CI, 2.1 to 7.3), in hypertensives (RR⫽3.6; 95% CI, 1.9 to
6.8), and in overweight men (RR⫽3.8; 95% CI, 2.0 to 7.1).
The respective risks of stroke were RR⫽3.8; 95% CI, 1.1 to
Kurl et al
Silent Ischemia and Stroke and Cardiovascular Risk
1763
TABLE 2. Risk of Stroke and Cardiovascular Disease Death According to the Presence of Silent
Myocardial Ischemia in an Exercise Electrocardiogram in Men With No Prior Coronary Heart Disease
and Stroke
Stroke Events (n⫽78)
Risk factor
CVD Death (n⫽86)
RR (95% CI)
P Value
RR (95% CI)
P Value
Silent myocardial ischemia during exercise*
2.18 (1.11–4.27)
0.023
3.48 (2.03–5.99)
⬍0.001
Silent myocardial ischemia during recovery*†
1.85 (0.66–5.13)
0.239
5.18 (2.72–9.88)
⬍0.001
*Each variable was entered separately into a Cox model with age, examination years, cigarette smoking, systolic blood pressure,
alcohol consumption, body mass index, diabetes, and serum LDL cholesterol.
†Silent myocardial ischemia during recovery was defined as horizontal or downsloping ST depression ⱖ1.0 mm at 80 ms after J
point or any ST depression of ⬎1.0 mm at 80 ms after J point after 5-minute recovery period.
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12.5 in smokers; RR⫽3.5; 95% CI, 1.7 to 7.4 in hypercholesterolemic men; and RR⫽3.4; 95% CI, 1.6 to 7.1 in
hypertensive men with any risk factor. All of these associations were statistically nonsignificant in men without any
conventional risk factors, except for nonsmokers with silent
ischemia during exercise, who also had an increased risk of
CVD death (RR⫽3.2, 95% CI, 1.6 to 6.4).
Silent ischemia during exercise had a strong association
with the risk of stroke in men with both hypertension and
hypercholesterolemia (RR⫽6.1, 95% CI; 2.4 to 15.4) and in
smokers with hypercholesterolemia (RR⫽5.6; 95% CI, 1.8 to
18.2), as well as in smokers with hypertension (RR⫽10.2;
95% CI, 2.5 to 42.7). The respective RRs for CVD death were
a 3.2-fold (95% CI, 1.7 to 6.0) increased risk for men with
hypertension and hypercholesterolemia, a 4.1-fold (95% CI,
1.9 to 9.0) increased risk for smokers with hypercholesterolemia, and a 8.4-fold (95% CI, 4.3 to 16.4) increased risk for
smokers with hypertension. In men with silent ischemia and
the presence of 3 conventional risk factors (hypertension,
hypercholesterolemia, and smoking), the RRs were a 4.9-fold
(95% CI, 1.51 to 15.9) increased risk for stroke and 5.8-fold
(95% CI, 2.3 to 14.7) increased risk for CVD death. However,
decreased statistical power limits the interpretation of the
results among the few asymptomatic subjects (n⫽18) with all
3 risk factors and silent ischemia during exercise.
This prospective, population-based study demonstrates that
silent myocardial ischemia during exercise, as indicated by
painless ST-segment depression on the ECG, is associated
with an increased risk of stroke and CVD death in asymptomatic, middle-aged men who have additional risk factors,
such as smoking, hypercholesterolemia, hypertension, and
being overweight.
The prognostic value of silent myocardial ischemia, as
indicated by exercise ECG findings, varies considerably in
previous studies,3,7,9,20,21 most likely because of different
selection criteria for the subjects. Most studies have included
only patients with CHD,1,5,6 whereas few studies have included persons without prior CHD.8,9,21 It has been argued
Figure 1. Cumulative hazards of cardiovascular mortality in men
with silent myocardial ischemia (high-risk group) during exercise
versus all others (low-risk group).
Figure 2. Cumulative hazards of stroke in men with silent myocardial ischemia (high-risk group) during exercise versus all others (low-risk group).
Silent myocardial ischemia in overweight men when combined with hypertension (5.8-fold risk) and hypercholesterolemia (3.6-fold risk) was related to the increased risk of stroke,
except for overweight smokers, who had no statistically
significant increased risk for stroke. Silent myocardial ischemia was related to a 3.9-fold (95% CI, 1.9 to 7.9) increased
risk for CVD death in overweight smokers, a 3.9-fold (95%
CI, 1.7 to 6.0) increased risk in overweight and hypertensive
men, and a 4.1-fold (95% CI, 1.7 to 10.3) increased risk in
overweight and hypercholesterolemic men.
Discussion
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July 2003
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Figure 3. RRs and (95% CIs) of CVD (a)
and stroke (b) in men with silent myocardial ischemia during exercise, according
to conventional risk factor levels. Men
with no myocardial ischemia were the
reference group. The cutoff value for
hypertension was 140/90 mm Hg; for
serum LDL cholesterol, 3.5 mmol/L; and
for overweight, BMI of 25 kg/m2. RRs
were adjusted for age, examination
years, alcohol consumption, BMI, diabetes, cigarette smoking, SBP, and serum
LDL, except for the risk factor of interest.
that the prognostic value of exercise ECG is low in totally
asymptomatic persons because of false-positive and falsenegative responders. However, in healthy individuals with a
high pretest probability of CHD, eg, in those with major CVD
risk factors, the frequency of false-positive test responses for
myocardial ischemia is lower than in those without coronary
risk factors, which diminishes the bias associated with falsepositive responders (the Bayes’ rule).7,22 This is consistent
with our results showing that the association between silent
myocardial ischemia with stroke and CVD risk was stronger
in high- than in low-risk groups. This finding is in accordance
with the approach of Diamond and Forrester, which demonstrated the role of other risk factors in modifying the
likelihood of future CVD among patients with or without
atypical angina.23
It has been suggested that risk assessment for primary
CHD is enhanced by detection of abnormal exercise ECG
findings only in those who have 1 or more conventional risk
factors.7 In the present study, men with silent myocardial
ischemia had a substantially increased risk for stroke and
CVD death if they had any of several other common risk
factors. Painless myocardial ischemia during exercise in the
presence of at least any 1 of these risk factors (smoking,
hypercholesterolemia, hypertension, or overweight) helps to
identify individuals who may benefit from intensive risk
factor reduction. Our results are in line with the recommendations that asymptomatic, high-risk individuals with any of
the major coronary risk factors should undergo ECG testing
to better define their risk for CHD.24,25
It is plausible that silent myocardial ischemia on ECG
testing is a reflection of advanced atherosclerosis, not only in
the coronary arteries but also in large arteries of the cerebral
circulation.12,13 Because atherosclerosis is the pathological
basis of occlusive cerebrovascular disease, it may partly
explain the association between exercise-induced myocardial
ischemia and stroke. CHD and stroke share several risk
Kurl et al
Silent Ischemia and Stroke and Cardiovascular Risk
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factors, and an association between atherosclerotic cerebrovascular disease and CHD has been established in several
studies.4,12,15 This may partially explain the association between exercise-related silent myocardial ischemia and stroke
found in high-risk individuals in the present study.
The use of a small, ST-segment depression as a diagnostic
criterion can decrease the test’s specificity because conditions
other than myocardial ischemia, such as hyperventilation,
electrolyte abnormalities, anemia, ventricular hypertrophy,
and increased sympathetic activity, are known to cause
ST-segment depression.9,19 One limitation of the present
study is that we studied only middle-aged men, and thus, our
findings may be not generalized to elderly and female
populations. Furthermore, exercise ECG testing is generally
used as an initial screening test that is followed by more
accurate methods, such as pharmacological echocardiography, myocardial perfusion imaging, positron emission tomography, and ambulatory ECG monitoring, and assessment of
the arteries by ultrasonography or magnetic resonance imaging.22,26,27 Our data do not address how frequently the patients
we identified with silent ischemic changes on exercise ECG
would benefit from these other tests.
In conclusion, our results do not support generalized
screening of low-risk populations with exercise ECG testing.
However, the finding of silent myocardial ischemia on
exercise testing in high-risk, asymptomatic men may help to
identify a subgroup at particularly high risk of stroke and
CVD death who may benefit from further evaluation and
intensive risk factor modification. Whether this would translate into improved health outcomes requires further study.
Acknowledgments
The present study was funded by the US National Heart, Lung, and
Blood Institute (Bethesda, Md; grant No. HL 44199), the Academy
of Finland, the Finnish Ministry of Education, the Juho Vainio
Foundation, the Finnish Foundation for Cardiovascular Research, the
Finnish Cultural Society of Northern Savo, and the Aarne Koskela
Foundation (Helsinki, Finland).
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Sivenius and J.T. Salonen
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Stroke. 2003;34:1760-1765; originally published online June 26, 2003;
doi: 10.1161/01.STR.0000078564.46376.0A
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