(Circulation. 1996;93:2097-2105.)
© 1996 American Heart Association, Inc.
Articles |
Diabetics With Coronary Disease Have a Prevalence of Asymptomatic Ischemia During Exercise Treadmill Testing and Ambulatory Ischemia Monitoring Similar to That of Nondiabetic Patients
An ACIP Database Study
Presented in part at the 43rd Scientific Session of the American College of Cardiology, Atlanta, Ga, March 14-18, 1993, and published in abstract form (J Am Coll Cardiol. 1994;23:318A).
From the St Louis (Mo) University Health Sciences Center (E.A.C., B.R.C.); the Maryland Medical Research Institute (S.A.F.), Baltimore; Brigham & Women's Hospital (P.H.S.), Boston, Mass; the Montreal (Quebec) Heart Institute (M.G.B.); the National Heart, Lung, and Blood Institute (G.S., N.L.G.), Bethesda, Md; and the University of Florida (C.R.C.), Gainesville.
Correspondence to Eugene A. Caracciolo, MD, Cardiac Catheterization Laboratory, St Louis University Health Sciences Center, 3635 Vista Ave and Grand Blvd, St Louis, MO 63110.
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Abstract |
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Background There are conflicting data as to whether diabetics have a higher prevalence of asymptomatic ST-segment depression during exercise treadmill testing (ETT) and ambulatory ECG (AECG) monitoring. This study was conducted to determine whether diabetic patients with coronary disease enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) have more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients and to compare differences in angiographic variables and the magnitude of ischemia as measured by standard ETT and AECG criteria.
Methods and Results Angiographic variables and the
prevalence and magnitude of ischemia during the qualifying ETT
and 48-hour AECG were compared by the presence and absence of diabetes
mellitus in 558 randomized ACIP patients. Seventy-seven patients
had a history of diabetes and were taking oral hypoglycemics or insulin
(diabetic group); 481 patients did not meet these criteria (nondiabetic
group). Multivessel disease (87% versus 74%, P=.01) was
more frequent in the diabetic group. The percentages of patients
without angina during the ETT were similar in the diabetic and
nondiabetic groups (36% and 39%, respectively). Time to onset of
1-mm ST-segment depression and time to onset of angina were similar
in both groups. The percentages of patients with only
asymptomatic ST-segment depression during the 48-hour
AECG were similar in the diabetic and nondiabetic groups (94% versus
88%, respectively). However, total ischemic time per 24 hours
(15.0±21.4 versus 23.6±31.1 minutes, P=.02),
ischemic time per episode (6.3±4.6 versus 9.0±8.7 minutes,
P<.01), and the maximum depth of ST-segment depression
tended to be less in the diabetic group.
Conclusions Patients enrolled in ACIP were selected on the basis of an abnormal ETT and 48-hour AECG and ability to undergo coronary revascularization. When patients with diabetes mellitus were compared with those without diabetes, there was a similar prevalence of asymptomatic ischemia during ETT and 48-hour AECG monitoring. Despite more extensive and diffuse coronary disease, diabetic ACIP patients tended to have less measurable ischemia during the 48-hour AECG.
Key Words: diabetes mellitus • coronary disease • ischemia • exercise
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Patients with diabetes mellitus are at significantly increased risk for the development of coronary atherosclerosis1 2 3 4 5 and may experience "silent" myocardial infarction in the absence of chest pain.6 7 8 9 10 11 However, there are conflicting data as to whether diabetic patients with coronary disease have a higher prevalence of asymptomatic ischemia during ETT and AECG monitoring compared with nondiabetic patients. Although some have reported a higher prevalence of asymptomatic ischemia in diabetic patients during ETT12 13 14 15 and AECG monitoring,15 others have shown a similar prevalence of asymptomatic ischemia in diabetic and nondiabetic patients during ETT.16 17 Development of an autonomic neuropathy that can be histologically characterized18 and physiologically demonstrated12 19 20 21 22 23 is postulated as a mechanism responsible for the defective anginal warning system attributed to diabetic patients.
The ACIP study is a National Heart, Lung, and Blood
Institute–funded international randomized trial designed to
compare the efficacy of three treatment strategies—(1)
angina-guided therapy, (2) angina-guided plus ambulatory AECG
ischemia–guided therapy, and (3)
revascularization therapy—to suppress
AECG-documented ischemia at 12 weeks of follow-up and to
assess the feasibility of conducting a larger clinical trial to
evaluate the effects of anti-ischemic therapy on morbidity
and mortality.24 The study results show that
asymptomatic ischemia is frequent and can be
suppressed in 
50% of patients with medication or
revascularization and that
revascularization was the most effective treatment
strategy to reduce ischemia. The pilot study demonstrated that
a large-scale clinical trial addressing the issue of the effect of
anti-ischemic strategy on long-term
cardiovascular morbidity and mortality is needed and
that a large clinical trial is feasible.25
The objective of this report was to address three clinically important questions among a group of patients selected for the presence of coronary disease, ischemia during an ETT, and asymptomatic ischemia during AECG monitoring: (1) Do diabetics have significantly more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients? (2) Are there measurable differences in the magnitude of ischemia evaluated by standard ETT and AECG monitoring in diabetic and nondiabetic patients? and (3) Are there measurable differences in angiographic variables that may explain the differences in ischemia manifestations between the two groups?
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Methods |
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The design of the ACIP study and baseline characteristics of patients recruited have been reported previously.24 26 Briefly, patients were eligible for inclusion into ACIP if they had objective evidence of stress-related ischemia during an ACIP protocol ETT, had at least one episode of asymptomatic ischemia during 48-hour AECG monitoring, and had one or more stenoses of
50% reduction in
lumen diameter in a major epicardial vessel suitable for
revascularization. The patients were ineligible if
they had undergone coronary artery bypass graft surgery within
the previous 3 months or coronary angioplasty within the
previous 6 months; had had a myocardial infarction in the previous 4
weeks; had unstable angina, left ventricular failure (New
York Heart Association functional class III or IV), or significant
noncardiac illnesses at the time of screening; were taking digitalis;
had a contraindication to ß-blocking or calcium channel blocking
agents; or had inadequate anginal control on medical therapy. The
screening ETT and 48-hour AECG were obtained after all
anti-ischemic medications except
nitroglycerin had been discontinued for at least 48
hours. Postinfarction patients and patients who required background
medication for control of their angina could continue to take either
atenolol or diltiazem SR.
Classification of Diabetes Mellitus
The major risk factors for coronary disease by patient
self-report were recorded at the time of randomization.
Clinical history of diabetes mellitus (yes/no/unknown) and current
therapy (oral agent/insulin/both/neither) were recorded. Ninety
patients (16%) claimed a clinical history of diabetes mellitus. Of
these, 13 patients were taking neither insulin nor oral medication at
the time of study entry. The 77 patients (14%) with a clinical history
of diabetes mellitus who were receiving insulin or oral agents
constitute the diabetic group in this analysis; all other
patients, including the 13 with a history of diabetes but on no
medication, constitute the nondiabetic group.
Coronary Angiography and Left
Ventriculography
Patients were eligible for ACIP if they had a 50% reduction
in lumen diameter as measured by electronic calipers in at least one
view in one or more major epicardial coronary arteries suitable
for revascularization. Major coronary
arteries were defined as the left anterior descending, left circumflex,
and right coronary arteries. Diagonal, circumflex marginal, and
posterolateral branches were considered major vessels if they supplied
a large enough area of myocardium suitable for
coronary artery bypass graft surgery or
percutaneous coronary angioplasty. Angiograms
were characterized by single-, double-, and triple-vessel
coronary artery disease. Angiographic flow distal to a
stenosis was graded by TIMI criteria (TIMI grade 0 to
3).27 Angiographic collateral flow to a vascular territory
distal to a stenosis was graded as grade 0 (no angiographic
collaterals visualized), grade 1 (minimal collaterals present with
minimal to partial filling of the recipient artery), or grade 2
(well-developed collaterals with near-complete to complete
filling of the recipient artery). For each patient, the maximal
collateral grade in any lesion was defined. Angiograms evaluated for
eligibility were obtained within the 3 years preceding screening,
provided that the patient did not have a subsequent clinical event. For
those patients with three-vessel coronary artery disease,
an angiogram performed within the previous 5 years was acceptable,
again provided that there was no intercurrent clinical event. Suitable
left ventricular systolic function was subsequently
confirmed by either echocardiography or
radionuclide ventriculography.
ACIP Protocol ETT
The symptom-limited ACIP exercise protocol was used; this
protocol produces a more linear increase in oxygen consumption
(
O2) than the Bruce
protocol.28 The walking speed of the ACIP protocol is set
at 3 miles/h, with two 1-minute warm-up stages followed by 2-minute
stages designed to increase workload by 1.5-MET increments from 2.5 to
15.1 METs. Criteria for ischemia-related ECG changes were
defined as (1) ST segment level 80 ms after the J-point (ST 80)
depression 1.0 mm, ST segment horizontal or downsloping <1 mV/s; or
(2) ST 80 depression 1.5 mm and ST segment upsloping >1 mV/s
compared with baseline.
48-Hour AECG Monitoring
All AECG monitoring sessions consisted of two consecutive
24-hour recordings on a two-channel AM ambulatory ECG
cassette device with automatic calibration. Leads monitored were those
that demonstrated the greatest ST-segment deviation during the exercise
test. Specific criteria used to ensure interpretable ST-segment
activity were normal sinus rhythm; QRS duration <0.1 second (except
for right bundle-branch block with isoelectric ST segments in the
lateral precordial leads); and no significant Q wave in the
monitored leads. The R-wave height was 15 mm in the lateral
precordial leads and 10 mm in the inferior leads.
Patients were excluded if ST-segment deviation of 1.0 mm occurred
during supervised postural maneuvers and hyperventilation.
Ischemic ST-segment depression was defined as 1 mm horizontal
or downsloping below the isoelectric line compared with the baseline
ST-segment value. Similarly, ischemic ST-segment elevation was
defined as 1 mm above the isoelectric line compared with the baseline
ST segment. An ischemic episode was defined as ST-segment
deviation 1 minute, and the episode duration was defined as the time
the ST-segment values deviated 1 mm. The ST segment had to have
returned to the baseline value for at least 5 minutes before new
ST-segment deviation was considered to represent a separate
ischemic episode.
Statistical Considerations
Differences between groups were analyzed by Student's
t test for continuous variables and the
2 test for categorical variables. The
percentage of patients with ischemic ST-segment depression
during the initial 10 minutes of the exercise test (9 METs) was
estimated by the Kaplan-Meier method29 30 ; patients who
did not complete 10 minutes of exercise for reasons other than
ST-segment depression were censored without the event at the time the
test was stopped. This analytical method was also used to estimate the
percentage of patients with angina during the initial 10 minutes of
exercise, mean time to angina onset, and mean time to onset of 1-mm
ST-segment depression.
Multivariate analyses of the relationship of AECG variables and ETT variables to the presence of diabetes were performed with adjustment for clinical, hemodynamic, and angiographic variables.
Power to detect differences between our patients with diabetes mellitus
versus those without diabetes is limited. As an example, if the outcome
is present among 50% of patients with diabetes, it would have to
be present in 
30% of patients without diabetes for there to be a
probability .8 to detect this difference when hypothesis testing is
conducted at the .01 significance level.
To take account of the many hypotheses tested in the ACIP study,
P=.01 was regarded as showing some evidence against the null
hypothesis, and P=.001 was regarded as strong evidence.
However, all values of P.05 are shown. The closure date
for the analysis file was July 8, 1994.
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Results |
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Data reported here are for 558 patients. All 60 patients from one clinical unit have been excluded as previously reported.31
Baseline Clinical and Hemodynamic
Characteristics
Of 558 randomized ACIP patients, 77 (14%) had a clinical history
of diabetes mellitus and were taking either insulin or oral
hypoglycemic agents (diabetic group). Four hundred eighty-one
patients (86%) did not meet these criteria (nondiabetic group) (Table 1
). Seventy percent of patients in both groups had
anginal symptoms at the time of study entry based on history, ETT, or
an ischemic episode with angina on the AECG (Table 1). A
clinical history of hypertension (55% versus 35%, P<.001)
was present more frequently in the diabetic group on study
enrollment (Table 1). ß-Adrenergic blocking agents were used more
frequently in nondiabetic than in diabetic patients (46% versus 32%,
respectively, P=.02), whereas
angiotensin-converting enzyme inhibitors
were used more commonly in diabetic than in nondiabetic patients (18%
versus 10%, respectively, P=.05) (Table 2).
Diabetic patients had a significantly higher basal heart
rate (72.9±11.1 versus 68.7±11.7 bpm, P=.003) and
systolic blood pressure (146.7±18.6 versus 137.6±19.3 mm Hg,
P<.001) than did the nondiabetic group (Table 1).
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Angiographic Data From the Qualifying
Catheterization
The time from the qualifying cardiac
catheterization to study enrollment was almost twice as
long in the diabetic group as in the nondiabetic group (160±313 versus
81±173 days, P<.01). More diabetic group patients had
three-vessel disease than nondiabetic group patients
(P=.03) (Table 3, Fig 1).
Additionally, diabetic patients had more diffuse coronary
disease as quantified by the number of lesions with a 50% reduction
in lumen diameter (Table 3, Fig 1). Approximately 40% of patients in
both groups had at least one occlusion with TIMI grade 0 distal flow.
Angiographic collateral grade was similar in both groups.
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Left ventricular ejection fraction (61.9±10.8% versus
60.7±9.8%) and the maximum percent stenosis (89.4±13.5%
versus 88.2±14.4%) were similar for the diabetic and nondiabetic
groups, respectively (Table 3
).
Qualifying ETT Results
During the ETT, the prevalences of patients without angina
were similar in the diabetic and nondiabetic groups (36% versus 39%,
respectively) (Table 4, Fig 2). There was
no significant difference in the final stage of exercise achieved
between the two groups. At peak exercise, the heart rate,
systolic blood pressure, and rate-pressure product were
similar for the diabetic and nondiabetic groups. At the time to 1-mm
ST-segment depression, the heart rates were similar but the
systolic blood pressures were higher in the diabetic group than
in the nondiabetic group patients (P=.03). The
rate-pressure product at the time to 1-mm ST-segment
depression was similarly higher in the diabetic than in the
nondiabetic group patients (21.8±4.4 versus 20.5±4.6 mm
Hg·bpmx10-3, respectively,
P=.02). Both groups had similar times to onset of 1-mm
ST-segment depression and times to onset of angina (Table 4).
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Diabetes was not an important correlate of the ETT variables (time to onset of angina, time to onset of 1-mm ST-segment depression, sum of ST depression) by univariate analysis, and it remained nonsignificant by multivariate analysis when clinical, hemodynamic, and angiographic variables were adjusted for.
Qualifying 48-Hour AECG Test Results
By study design, all patients had at least one episode of
asymptomatic ambulatory ischemia during the
qualifying 48-hour AECG. The percentages of patients with only
asymptomatic episodes were similar in the diabetic and
nondiabetic groups (94% versus 88%, respectively, P=NS)
(Fig 2, Table 5). There was no significant difference in
the distribution of ischemic episodes between the two
groups.
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Hemodynamically, the maximum heart rates recorded
during ischemic episodes were similar for diabetic and
nondiabetic group patients (116±16.6 versus 119±19.1 bpm,
P=NS). Total ischemic time per day (15.9±21.4
versus 23.6±31.1 minutes, P=.02), minutes per episode
(6.3±4.6 versus 9.0±8.7 minutes, P=.009), and mean depth
of the ST-segment depression (1.7±0.7 versus 2.1±0.9 mm,
P=.004) all tended to be less in the diabetic group (Table 5). However, diabetes was a nonsignificant correlate of the AECG
variables by multivariate analysis when
clinical, hemodynamic, and angiographic
parameters were adjusted for.
In an attempt to define a surrogate variable of daily life
activity, comparison of the maximal heart rate during the AECG as a
percentage of the heart rate at ischemia onset during the ETT
was performed. In the diabetic group, the maximal heart rate during the
AECG as a percentage of the heart rate at ischemia onset during
the ETT was lower than in the nondiabetic group (Table 6).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study compared the diabetic and nondiabetic patients enrolled in ACIP with respect to angiographic variables and the prevalence and magnitude of ischemia. It is the first published report of a large cohort of patients with complete angiographic, ETT, and AECG data sets available. Diabetic ACIP patients did not have a higher prevalence of asymptomatic ischemia during the qualifying ETT and 48-hour AECG monitoring than nondiabetics. Surprisingly, the diabetic group tended to have less measurable ambulatory ischemia quantified by total ischemic time per day, ischemic time per episode, and maximal depth of ST-segment depression during the 48-hour AECG, even though coronary disease was more extensive and diffuse in the diabetic group, and the times to onset of 1-mm ST-segment depression and angina during the ETT were similar between the diabetic and nondiabetic groups.
Clinical and Angiographic Variables
Hypertension is present more commonly in diabetic than in
nondiabetic patients. In one prospective study, hypertension was
detected in more than half the diabetic patients >45 years of
age.32 Similarly, 55% of diabetic ACIP patients had a
history of hypertension, and the resting systolic blood
pressure was significantly higher in the diabetic than in the
nondiabetic group at study enrollment.
Hypercholesterolemia was reported in a similar
percentage of diabetic and nondiabetic patients, similar to results in
the Framingham study.2
In the literature on patients with known coronary artery disease, the extent of disease is more severe in diabetic than in nondiabetic patients.33 Patients with diabetes have a higher incidence of triple-vessel disease34 35 36 and may also have more diffuse coronary disease than nondiabetic patients,37 although this issue remains unsettled.34 38 These findings are corroborated by ACIP patients, even though the interval between cardiac catheterization and study enrollment was longer in the diabetic group and therefore may have underestimated the extent of disease at the time of study entry. ACIP diabetic and nondiabetic patients had similar ejection fractions, numbers of occluded vessels, and prevalences of myocardial infarction, angina, and surgical and nonsurgical revascularization before enrollment. Although ACIP patients were selected on the basis of specific ETT and AECG criteria and eligibility for coronary revascularization, their baseline clinical and angiographic variables are similar to reported natural history studies of diabetic and nondiabetic patients.
Asymptomatic Ischemia in Diabetic
Patients
Since Bradley and Schonfeld11 first reported
comparisons of clinical manifestations of acute myocardial infarction
in diabetic and nondiabetic patients in 1962, it has been generally
accepted that diabetic patients often present with less severe
chest pain than nondiabetic patients and that their presenting
symptoms of cardiac events are frequently unrelated to chest
pain.8 The data from the Framingham study confirmed that
truly silent myocardial infarction, as documented by biennial ECGs,
occurs in 12% of patients and is more common in diabetic
patients.6 9 These clinical findings are supported by
autopsy data from patients without a clinical history of myocardial
infarction, showing that myocardial scar is more likely to be
present in diabetics than nondiabetics.7 10
Histological changes in intracardiac sympathetic and
parasympathetic afferent fibers18 are often cited as a
potential mechanism for the diminished, altered, or absent sensation of
chest pain experienced by diabetic patients with acute myocardial
infarction.
As an extension of these data, several investigators have reported that diabetics with known coronary disease and in unselected series have a higher prevalence of asymptomatic ischemia during ETT than do nondiabetic patients.12 13 14 15
ETT Data
Nesto et al14 compared 50 diabetic patients with 50
nondiabetic patients, all of whom had evidence of myocardial
ischemia by exercise thallium scintigraphy.
Although clinical characteristics, total exercise duration, and peak
work double product were similar in the two groups, only 28% of
the diabetic patients experienced angina during the treadmill test
compared with 68% of the nondiabetic patients. However, in 20% of the
diabetic and 8% of the nondiabetic patients, the test was terminated
when 1 mm of ST-segment depression was reached. Additional patients in
both groups might have developed angina if they had exercised
longer.
The relationship between the time to 1-mm ST-segment depression and the
total exercise time has been compared in diabetic and nondiabetic
patients with known coronary artery disease.39 40
Defined as the anginal perceptual threshold, the perception of angina
after the onset of ischemic ST-segment depression was
significantly delayed in diabetics and was manifested by a
significantly shorter time to 1-mm ST-segment depression in the
diabetic group, with similar time to angina onset and total exercise
time in both groups.39 40 In ACIP, 60% of
patients in both the diabetic and nondiabetic groups experienced angina
during the exercise test. Because the time to onset of 1-mm ST-segment
depression and the time to onset of angina (for those patients who
experienced angina) were similar in both groups, the anginal perceptual
threshold was not prolonged.
The ACIP ETT data are supported by data from the CASS registry.41 Among 1434 CASS registry patients with documented coronary disease who had symptom-limited exercise testing within 1 month of cardiac catheterization, there were 113 patients with a clinical history of treated diabetes mellitus and 1321 nondiabetic patients. Although the diabetic group had more severe coronary disease, the prevalence of exercise-induced asymptomatic ischemia was similar in the diabetic and nondiabetic groups (40% and 33%, respectively).
In unselected series of patients without known coronary
disease, Naka et al13 compared the prevalence of
asymptomatic ischemia in 132 diabetic and 140
nondiabetic patients during a symptom-limited ETT. None of the
patients in either group experienced chest pain, although 30% of
patients in both groups had ischemic ST-segment changes.
However, 39% of the diabetic group had angiographic coronary
disease, which was significantly greater than the 18% in the
nondiabetic group. However, two retrospective studies did not find such
differences. Chipkin et al17 reported that the prevalence
of asymptomatic ischemia during ETT was not
significantly different in diabetic and nondiabetic patients (54% and
47%, respectively). Similarly, Callaham et al16 reported
that 62% of diabetic patients with an ischemic ST response
during ETT had no chest pain, similar to the 60% of nondiabetic
patients.
AECG Data
Many patients with coronary disease and a positive
exercise test have episodes of ST-segment depression during ambulatory
monitoring, the majority of which are silent.42 43 44 45 46 47 48 49
Surprisingly, ambulatory ischemia monitoring has not been
widely applied in the assessment of asymptomatic
ischemia in diabetics. Chiariello et al15 compared
the incidence of ambulatory ischemia during 24-hour AECG
monitoring among 51 patients with diabetes (74% of whom had evidence
of coronary disease), 70 nondiabetic patients with
coronary disease, and 40 nondiabetic patients without overt
coronary disease. They reported that 36% of the diabetic
patients had at least one episode of asymptomatic
ischemia, significantly higher than the 17% of patients in the
nondiabetic group with coronary disease. Additionally, 73% of
the total episodes of ST-segment deviation in the diabetic group were
asymptomatic, significantly higher than the 60% of
episodes in the nondiabetic group. These data cannot be directly
compared with ACIP patients, who all had at least one episode of
asymptomatic ST-segment deviation by study design. In
ACIP, 90% of patients had only asymptomatic
ST-segment depression during the qualifying 48-hour AECG
recording. There was no difference in the prevalence of
asymptomatic ST-segment depression in the diabetic and
nondiabetic ACIP groups.
Although the distribution of ischemic episodes was similar in
the ACIP diabetic and nondiabetic groups, the diabetic group tended to
have less measurable ischemia. An explanation for this trend is
not readily apparent. Angiographically, more patients in the diabetic
group had three-vessel disease and more diffuse coronary
disease than in the nondiabetic group. Hemodynamically,
the elevated systolic blood pressure recorded in the
diabetic group at study enrollment may have been postulated, a priori,
to contribute to a greater magnitude of ambulatory ischemia in
the diabetic group. Clinically, the diabetic group was initially judged
likely to be as active as the nondiabetic group, since both groups had
similar exercise capacity, work double product, and maximum heart
rate during the ETT. Additionally, there were no differences in the
mean heart rate or maximum heart rate during the entire 48-hour
monitoring session. However, in the diabetic group, the maximal heart
rate during the AECG as a percentage of the heart rate at
ischemia onset during the ETT was lower, suggesting that
perhaps the diabetic group was, in fact, less active than the
nondiabetic group (Table 6).
A number of investigations have focused on the possible mechanism of ambulatory ischemia. An increase in heart rate preceding ST-segment depression has been reported by some42 43 50 51 52 53 but not all15 48 54 investigators, suggesting increased myocardial oxygen demand. Similarly, an increase in systolic blood pressure preceding ST-segment depression has also been reported.43 55 Deedwania and Nelson43 showed that although the majority of ambulatory ischemic events were preceded by an increase in both the heart rate and systolic blood pressure, a significant number of events occurred without an increase in the two major measurable determinants of myocardial oxygen demand and thus were assumed to occur from coronary vasomotion. Andrews et al50 extended these findings by showing that the likelihood of developing ischemia was predicted by heart rate variables, including the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate. Additionally, they showed that the efficacy of ß-adrenergic blocking therapy was in general related to reducing these same heart variables, whereas nifedipine was more effective in reducing the number of ischemic episodes not associated with preceding periods of increased heart rate. The contribution of vasomotor tone to the genesis of ambulatory ischemia is further supported by the observation that the onset of ST-segment depression during AECG monitoring is lower than the heart rate at the onset of ST-segment depression during exercise testing.43 44 45 46 47 48 49
Study Limitations
The ACIP population constitutes a well-defined cohort of
patients with documented ischemia during both ETT and
ambulatory monitoring and coronary disease amenable to
revascularization. During screening for ACIP,
36% of patients with an ischemic response during AECG
monitoring were ineligible for ACIP. Since the clinical history of
diabetes mellitus was obtained only on randomization, the diabetic
state of these additional ACIP-ineligible patients is unknown.
ACIP data may not be comparable to previous studies, since all patients enrolled in ACIP had stable documented coronary disease and asymptomatic cardiac ischemia. The ETT and AECG data were retrospectively analyzed by the presence or absence of diabetes mellitus. A study of ACIP patients is not equivalent to a study comparing unselected patients with and without diabetes mellitus without a previous history of coronary disease or chest pain.
Clinical Implications
ACIP patients with diabetes mellitus have more extensive and
diffuse coronary disease, a similar prevalence of
asymptomatic ischemia during both ETT and
48-hour AECG monitoring, and less measurable ischemia during
AECG monitoring than do nondiabetic ACIP patients. Although these data
are not generalizable to diabetic patients without documented
coronary disease, our study shows that diabetic ACIP patients
become ischemic at a similar rate-pressure product and
have a similar exercise capacity but do not have a higher prevalence of
asymptomatic ischemia and may be less active
throughout the day. In light of their predominantly
asymptomatic manifestation of coronary disease,
these patients may require closer clinical surveillance to alleviate
myocardial ischemia.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by research contracts HV-90-07, HV-90-08, and HV-91-05 to HV-91-14 from the National Heart, Lung, and Blood Institute, Bethesda, Md.
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Footnotes |
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Reprint requests to ACIP Clinical Coordinating Center, Maryland Medical Research Institute, 600 Wyndhurst Ave, Baltimore, MD 21210.
1 A list of participating centers and investigators appears in Reference 26.26 
Received September 20, 1995; revision received January 24, 1996; accepted January 29, 1996.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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