From the Cardiovascular Health Branch, National Center for Chronic
Disease Prevention and Health Promotion, Centers for Disease Control and
Prevention, Atlanta, Ga (W.H.G., J.B.C.), and the Division of Neurosciences
Critical Care, the Johns Hopkins Hospital, Baltimore, Md (A.I.Q.).
Correspondence to Wayne H. Giles, MD, MS, Cardiovascular Health Branch, CDC, 4770 Buford Hwy, MS K-47, Atlanta, GA 30341. E-mail HWG0{at}CDC.GOV
Methods—We evaluated the association between IGT (defined as a
fasting glucose level of <140 mg/dL and a plasma glucose level of
between 140 and 200 mg/dL 2 hours after administration of 75 grams of
an oral glucose load) and DM (defined as the current use of insulin or
an oral hypoglycemic medication, a fasting plasma glucose level of
>140 mg/dL, or a plasma glucose level of >200 mg/dL 2 hours after
administration of an oral glucose load) with a self-reported physician
diagnosis of stroke and myocardial infarction in 6547 adults aged 40 to
74 years participating in the Third National Health and Nutrition
Examination Survey. Multivariate logistic regression
analyses were used to investigate these relationships.
Results—IGT and DM were observed in 1494 and 1532 adults,
respectively. After adjustment for differences in age, gender,
race/ethnicity, education, hypertension, cholesterol, body
mass index, and cigarette smoking, IGT was not associated with stroke
(odds ratio [OR], 0.9; 95% confidence interval [CI], 0.5 to 1.6)
or myocardial infarction (OR, 1.1; 95% CI, 0.7 to 1.6). DM was
associated with both stroke (OR, 1.6; 95% CI, 1.0 to 2.6) and
myocardial infarction (OR, 1.9; 95% CI, 1.3 to 2.8).
Conclusions—In contrast to DM, IGT was not associated with an
increased likelihood of prevalent nonfatal stroke or myocardial
infarction.
NHANES III participants who were examined at the mobile examination
center and who were not current users of insulin or oral hypoglycemic
medications underwent a 2-hour, 75-g oral glucose tolerance test.
Examinees provided a fasting glucose blood specimen and then were
administered an oral glucose challenge (Dextol-75) containing the
equivalent of 75 g of glucose. A second specimen was drawn 2 hours
after the first.
Participants were judged to have DM if they were current users of
insulin or oral hypoglycemic medication, if they had a fasting plasma
glucose concentration >140 mg/dL, or if they had a plasma glucose
>200 mg/dL 2 hours after administration of the 75-gram glucose
challenge.6 7 Participants were defined as having
IGT if they had a fasting blood glucose <140 mg/dL and a plasma
glucose between 140 and 200 mg/dL 2 hours after administration of the
oral glucose challenge. Normal glucose tolerance (NGT) was defined as a
fasting and 2- hour-postchallenge glucose value < 140 mg/dL.
During the household interview participants were asked whether they had
ever been told by a physician that they had suffered a stroke or heart
attack; persons who answered in the affirmative were defined as having
the condition. Potential confounders in the association between IGT and
stroke and myocardial infarction included age, gender, race/ethnicity,
education, hypertension, cholesterol, body mass index
(weight [kg]/height [m2]), and cigarette
smoking. Subjects were judged to be hypertensive if they were current
users of antihypertensive medication or if they had an average blood
pressure greater than or equal to 140/90 mm Hg. This average
blood pressure was based on 3 blood pressure determinations obtained
during the medical examination.
t tests and
The unadjusted prevalence of nonfatal stroke was higher among the IGT
and DM groups than the NGT group (Table 2
The prevalence of nonfatal myocardial infarction was also higher among
the IGT and DM groups than the NGT group (Table 3
A number of studies have investigated the incidence and prevalence of
CVD in subjects with IGT.9 10 11 12 13 All of these
studies used a standardized glucose tolerance test to evaluate
hyperglycemic status, maintain uniform criteria, and avoid the biases
associated with self-reported diagnosis. Although there are multiple
studies of European origin,9 11 12 13 14 relatively
few studies have been conducted in the United
States.10 A cross-sectional study in Gothenburg
found that only hypertension and heart failure were significantly
associated with IGT; angina pectoris and stroke were not associated
with IGT.9 A Colorado study found an increased
prevalence of coronary heart disease in non-Hispanic white
persons with IGT but no association in persons of Hispanic
origin.10 The Paris Prospective Study evaluated
glucose tolerance among 7038 men aged 43 to 54 with no previous
cardiovascular disease.11 After
11 years of follow-up, persons with IGT at baseline evaluation had
approximately twice the risk of CVD mortality as did those with NGT.
The Whitehall study, which followed 18 403 men aged 40 to 60 years for
18 to 20 years, also found that subjects with IGT had approximately
twice the risk of CVD mortality as those with
NGT.12 However, because 2% to 16% of persons
with IGT progress into overt DM annually,14 15
the increased risk for CVD noted in prospective studies, especially
those of long duration, is likely to be confounded by the undocumented
development of DM during follow-up. This finding is supported by
results from a Finnish study of elderly men aged 65 to 84 years, which
reported no excess risk for CVD mortality in persons with IGT during a
5-year follow-up.13 In addition to study
duration, another potential explanation for the lack of an association
between IGT and CVD may be subject age. Our study population included
elderly persons, a subgroup in which two other Finnish studies also
failed to demonstrate any association between IGT and
CVD.13 16
The present study reported a higher prevalence of hypertension and
a higher mean cholesterol level in those with IGT compared
with those who had NGT. These findings are consistent with
previous studies that have demonstrated an increased frequency of CVD
risk factors in persons with IGT.17 18 The
increased prevalence of CVD risk factors among persons with IGT may
have confounded the association between IGT and CVD reported in other
studies. This finding is further supported by our observation–before
the adjustment for age and CVD risk factors–of an increased prevalence
of both stroke and myocardial infarction in persons with IGT. This
association disappeared after we adjusted for the confounding of age
and other CVD risk factors.
This report is subject to a number of potential limitations. The
definition of stroke and myocardial infarction used in the NHANES III
survey was based on a self-reported physician diagnosis. O'Mahony et
al19 validated the accuracy of assessing lifetime
history of stroke in a random sample of 2000 persons aged 45 years and
older using a mailed questionnaire. In that study, the accuracy of the
participants' self-reports of stroke was confirmed by a review of
their medical records. The sensitivity of the question was 95%,
and the specificity was 96%. Similarly high sensitivities (74% to
100%) and specificities (94% to 99%) have been reported for
estimations of prevalent myocardial
infarction.20 21 The questions on myocardial
infarction and stroke in the NHANES III survey may in fact be more
specific because not only was a physician diagnosis inquired, but the
information was acquired during a personal interview rather than a
mailed survey. Finally, the methodology used in this study did not
permit us to evaluate the likelihood for fatal stroke and myocardial
infarction. Fatal strokes and myocardial infarctions represent
less than one third of all cardiovascular disease
events.22 23 24 25 The exclusion of fatal events may
have reduced our ability to detect significant differences; it is
possible that IGT could be associated with only fatal
cardiovascular disease events. However, previous
studies have failed to demonstrate an association between diabetes
mellitus and fatal stroke.26 27
In conclusion, we were unable to demonstrate any association between
IGT and either prevalent stroke or myocardial infarction in a
nationally representative sample of US adults although
the relationship between DM and cardiovascular disease
was clearly demonstrable. Previous studies reporting such a
relationship may not have fully taken into account many of the
cardiovascular disease risk factors that may have
confounded this association.
Received January 22, 1998;
revision received April 17, 1998;
accepted April 17, 1998.
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© 1998 American Heart Association, Inc.
Original Contributions
Impaired Glucose Tolerance and the Likelihood of Nonfatal Stroke and Myocardial Infarction
The Third National Health and Nutrition Examination Survey
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and
Purpose—Although diabetes mellitus (DM) is known to increase the
risk of cardiovascular disease (CVD), the effect of
impaired glucose tolerance (IGT) on the risk remains unclear. We
determined whether IGT was associated with an increased likelihood for
stroke and myocardial infarction in a nationally
representative sample of US adults.
Key Words: diabetes mellitus • glucose tolerance • myocardial infarction • stroke
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
An association
between asymptomatic hyperglycemia and CVD was suggested in
1979 in a series of papers by the International Collaborative Group,
including a collective analysis of 15 studies, that examined
the relationship between IGT and CVD.1 2 More
recently, it has been hypothesized that hyperglycemia below the level
characteristic of DM may also be associated with an increased risk of
CVD.3 However, most of the studies describing an
association between IGT and CVD were performed in populations of
European origin in which CVD was found to be more prevalent in subjects
with IGT than in normoglycemic controls.3
Controversy exists regarding whether the relationship between IGT and
CVD is causal or results from common
antecedents.3 Because the prevalence of IGT and
the rate of progression to DM varies widely among
populations,4 we performed this study to
analyze the independent association between IGT and nonfatal
stroke and myocardial infarction in a nationally
representative sample of US adults.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The Centers for Disease Control and Prevention conducted the
Third National Health and Nutrition Examination Survey between 1988 and
1994 to estimate the prevalence of common chronic conditions and
associated risk factors among a nationally
representative sample of the civilian,
noninstitutionalized US population.5 NHANES III
included a household interview; a medical examination at a mobile
examination center; and phlebotomy to measure a number of hematologic
factors, including glucose and cholesterol. The study
sample included 6547 persons aged 40 to 74 years who participated in
the NHANES III survey at the mobile examination center. 
2 tests were used to
compare groups defined by glucose tolerance.
Multivariate logistic regression analyses were
used to determine whether the likelihood of myocardial infarction or
stroke differed by glucose tolerance. The logistic regression model
adjusted for the following CVD risk factors: age, gender,
race/ethnicity, education, hypertension, cholesterol, body
mass index, and smoking status. To take into account the complex
sampling design in the NHANES III survey, SUDAAN8
was used to obtain standard errors for the prevalence estimates and
ORs.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
A total of 6547 adults aged 40 to 74 years either had DM or
underwent the oral glucose tolerance test. A total of 1494 persons had
IGT and 1532 had DM. Compared with persons with NGT, those with IGT or
DM were older and had fewer years of education; had higher mean body
mass index, cholesterol, and serum glucose values; and were
more likely to be hypertensive (Table 1
).
The IGT and DM groups were less likely to be current smokers, while the
NGT group was more likely to include men. The racial/ethnic composition
of persons with IGT was similar to that for persons with NGT; by
contrast, there was a higher proportion of Hispanics among the DM group
than the NGT group.
View this table:
[in a new window]
Table 1. Characteristics of Subjects by Glucose Tolerance:
NHANES III, 1988–1994 ). However, the age-adjusted likelihood
of stroke was similar for the IGT and the NGT groups (OR, 0.9; 95% CI,
0.5 to 1.7). By contrast, persons with DM had a significantly greater
likelihood of nonfatal stroke than did persons with NGT (OR, 1.8; 95%
CI, 1.1 to 3.0). Adjustment for other CVD risk factors did not
substantially alter the risk estimates.
View this table:
[in a new window]
Table 2. Association Between Abnormal Glucose Tolerance and
Nonfatal Stroke: NHANES III, 1988–1994 ). However, the age-adjusted likelihood
of myocardial infarction for persons with IGT (OR, 1.1; 95% CI, 0.7 to
1.6) was similar to that for persons with NGT. In contrast, persons
with DM had a significantly greater likelihood of myocardial infarction
than did persons with NGT (OR, 2.0; 95% CI, 1.4 to 3.0). These
relationships remained after adjusting for CVD risk factors.
View this table:
[in a new window]
Table 3. Association Between Abnormal Glucose Tolerance and
Nonfatal Myocardial Infarction: NHANES III, 1988–1994
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Since the introduction of IGT as a diagnostic
category, there has been considerable interest in the possibility that
IGT might be associated with an increased risk of CVD, similar to the
relationship between diabetes mellitus and CVD. This study in a
nationally representative sample of US adults was
unable to demonstrate any association between IGT and nonfatal stroke
and myocardial infarction after the adjustment for age and CVD risk
factors.
Selected Abbreviations and Acronyms
CI
=
confidence interval
CVD
=
cardiovascular disease
DM
=
diabetes mellitus
IGT
=
impaired glucose tolerance
NGT
=
normal glucose tolerance
NHANES III
=
Third National Health and Nutrition Examination Survey
OR
=
odds ratio
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Alberti KG. The clinical implications of impaired
glucose tolerance. Diabet Med. 1996;13:927–937.[Medline]
[Order article via Infotrieve]
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