Prognostic Value of Admission Fasting Glucose Levels in Patients

With Acute Coronary Syndrome

Louis Kolman, MDa, Yu-Chen Hu, MDb, Daniel G. Montgomery, BSc, Kelly Gordonc,
Kim A. Eagle, MDa,c,d, and Elizabeth A. Jackson, MD, MPHa,c,d,*
Data are limited regarding the best prognostic glucose measure for patients admitted for an
acute coronary event. We examined the admission fasting glucose levels among patients
with acute coronary syndrome (ACS) from the University of Michigan ACS registry. The
glucose levels were grouped into 3 categories (>70 to <100, 100 to <126, and >126 mg/dl).
The primary outcome measures included mortality and a composite end point (stroke,
recurrent infarction, and death) in hospital and at 6 months after the ACS event. Of the
1,525 patients (29% with diabetes) for whom glucose levels were available, a fasting glucose
level of >100 mg/dl was associated with increased in-hospital mortality, after adjusting for
the Global Registry of Acute Coronary Events risk score and gender. A fasting glucose level
of >126 mg/dl in patients with no known history of diabetes was associated with in-hospital
adverse events (odds ratio 3.37, 95% confidence interval 1.51 to 7.51). The fasting glucose
level was associated with an increased risk of 6-month mortality among nondiabetics (odds
ratio 3.03, 95% confidence interval 1.35 to 6.81 for patients with a glucose level of 100 to
125 mg/dl; and odds ratio 2.81, 95% confidence interval 1.07 to 7.36 for patients with a
glucose level of >126 mg/dl) but not for diabetic patients. In conclusion, we observed a
strong association between the admission fasting glucose level and mortality, particularly
among nondiabetic patients. Whether improving the diagnosis and treatment of hypergly-
cemia would result in reductions in adverse events after ACS remains unclear. © 2009
Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:470 – 474)

The Acute Coronary Syndrome (ACS) Registry from the
University of Michigan Health System includes information
on the presentation, management, and follow-up of men and
women admitted with ACS, thus providing real-world data
on glucose measures and ACS outcomes. Using these data,
we examined whether the first fasting admission glucose
level was associated with adverse outcomes during the in-
dex hospitalization and 6 months after the ACS event
among diabetic and nondiabetic men and women.
Methods
The study population included all patients who were
admitted to the University of Michigan Health System from
January 1, 1999 to December 31, 2004 with a diagnosis of
ACS, for whom the admission fasting glucose level was
available (n ⫽ 1,541). Information on hemoglobin A1c was
a
Department of Internal Medicine, University of Michigan Health Sys-
tem, Ann Arbor, Michigan; bCalifornia Pacific Medical Center, San Fran-
cisco, California; cDivision of Cardiovascular Medicine, University of
Michigan Health System, Ann Arbor, Michigan; and dUniversity of Mich-
igan Health System, University of Michigan, Ann Arbor, Michigan. Manu-
script received February 16, 2009; revised manuscript received and ac-
cepted April 6, 2009.
This study was partly supported by unrestricted grants from the Mar-
digan Fund, Detroit, Michigan, Sanofi-Aventis, Bridgewater, New Jersey,
and the Hewlett Foundation, Menlo Park, California. Dr. Jackson was
supported by Grant K23 HL073310-01 from the National Heart, Lung, and
Blood Institute, Bethesda, Maryland.
*Corresponding author: Tel: (734) 998-7411; fax: (734) 998-9587.
E-mail address: lisjacks@umich.edu (E.A. Jackson).
not included because of the large numbers of subjects with
missing data. We chose to examine fasting glucose because
this measure also provides information on patients who
have levels consistent with a diagnosis of diabetes, irres-
pective of a history of diabetes. Patients ⬍18 years old
and those with noncardiovascular causes for the ACS
such as trauma, surgery, or aortic aneurysm were ex-
cluded from the present study. Full details of the Univer-
sity of Michigan Health System’s ACS registry have been
previously published.1
Patients were followed up at 6 months by telephone,
clinic charts, and/or medical records. Data were collected by
trained study coordinators using standardized case report
forms. The demographic characteristics, medical history,
presenting symptoms, biochemical and electrocardiographic
findings, and treatment practices and a variety of hospital
outcome data were collected. Standardized definitions of all
patient-related variables, clinical diagnoses, and hospital
complications and outcomes were used.1,2 All cases were
assigned to 1 of the following categories: ST-segment ele-
vation myocardial infarction, non–ST-segment elevation
myocardial infarction, or unstable angina. Patients were
diagnosed with ST-segment elevation myocardial infarction
when they had new or presumed new ST-segment elevation
⬎1 mm seen in any location or new left bundle branch
block on the index or subsequent electrocardiogram with
ⱖ1 positive cardiac biochemical marker of necrosis (including
troponin measurements, whether qualitative or quantitative).
For non–ST-segment elevation myocardial infarction, ⱖ1
positive cardiac biochemical marker of necrosis without
new ST-segment elevation seen on the index or subsequent

0002-9149/09/$ – see front matter © 2009 Elsevier Inc. All rights reserved. www.AJConline.org
doi:10.1016/j.amjcard.2009.04.006
 Coronary Artery Disease/Prognostic Value of Glucose Levels 471

Table 1
Baseline characteristics stratified by admission fasting glucose level
Characteristic Fasting Glucose (mg/dl) p Value

ⱖ70–⬍100 (n ⫽ 631) 100–125 (n ⫽ 499) ⱖ126 (n ⫽ 411)

Age (years) 62.5 ⫾ 14.4 64.1 ⫾ 13.6 65.1 ⫾ 13.5 0.009

Men 215 (34.1%) 162 (32.5%) 162 (39.4%) 0.08
White 503 (79.8%) 393 (78.8%) 334 (81.7%) 0.55
Body mass index (kg/m2) 28.7 ⫾ 9.0 30.0 ⫾ 7.0 30.5 ⫾ 6.8 0.002
Current smoker 161 (25.6%) 128 (25.7%) 86 (21.1%) 0.19
Family history of CAD* 299 (47.4%) 247 (49.6) 155 (37.8%) 0.001
Previous angina pectoris 242 (38.5%) 158 (31.7%) 170 (41.7%) 0.006
Previous heart failure 109 (17.4%) 64 (12.8%) 103 (25.4%) ⬍0.001
Previous myocardial infarction 282 (44.8%) 186 (37.3%) 185 (45.3%) 0.02
Previous revascularization 290 (46.1%) 196 (39.3%) 160 (39.1%) 0.03
Previous stroke 61 (9.7%) 43 (8.6%) 49 (12.0%) 0.23
Hyperlipidemia† 420 (66.7%) 314 (63.1%) 262 (64.2%) 0.43
Diabetes mellitus 89 (14.1%) 101 (20.2%) 269 (65.5%) ⬍0.0001
Peripheral vascular diseases 74 (11.8%) 63 (12.7%) 59 (14.4%) 0.45
Hypertension 418 (66.6%) 361 (72.3%) 333 (81.8%) ⬍0.001
Renal insufficiency 82 (13.0%) 73 (14.6%) 76 (18.6%) 0.05
ACS type
STEMI 132 (20.9%) 145 (29.1%) 96 (23.4%) ⬍0.01
NSTEMI 380 (60.2%) 274 (54.9%) 255 (62.0%) 0.07
Unstable angina pectoris 119 (18.9%) 80 (16.0%) 60 (14.6%) 0.17

Data are presented as mean ⫾ SD or numbers (%).

* Family history of CAD is defined as any direct blood relatives (parents, siblings, children) with a history of angina, myocardial infarction, or sudden
cardiac death without obvious cause.
†
Hyperlipidemia is defined as previously diagnosed hyperlipidemia or use of lipid-lowering medication at hospital admission.
CAD ⫽ coronary artery disease; NSTEMI ⫽ non–ST-segment elevation myocardial infarction; STEMI ⫽ ST-segment elevation myocardial infarction.

Table 2
In-hospital management according to admission fasting glucose
Variable Fasting Glucose (mg/dl) p Value

ⱖ70–⬍100 (n ⫽ 631) 100–125 (n ⫽ 499) ⱖ126 (n ⫽ 411)

Management
Thrombolytics 24 (3.8%) 26 (5.2%) 20 (4.9%) 0.50
Percutaneous coronary intervention 302 (47.9%) 257 (51.5%) 194 (47.4%) 0.38
Coronary artery bypass graft 57 (9.0%) 59 (11.8%) 50 (12.2%) 0.18
Admission medications
Aspirin 353 (55.9%) 263 (52.7%) 245 (59.6%) 0.11
␤ blockers 300 (47.5%) 246 (49.3%) 229 (55.7%) 0.03
Clopidogrel/ticlopidine 133 (21.1%) 86 (17.2%) 82 (20.0%) 0.25
Statins 300 (47.6%) 208 (41.7%) 201 (49.1%) ⬍0.05
Angiotensin-converting enzyme inhibitors 259 (41.1%) 215 (43.1%) 194 (47.4%) 0.13
(or angiotensin receptor blockers)
Discharge medications
Aspirin 605 (95.9%) 470 (94.2%) 375 (91.2%) 0.008
␤ blockers 563 (89.2%) 456 (91.4%) 352 (85.6%) 0.022
Statins 544 (86.2%) 418 (83.8%) 326 (79.3%) 0.013
Angiotensin-converting enzyme inhibitors 409 (64.8%) 334 (66.9%) 273 (66.4%) 0.74
(or angiotensin receptor blockers)

electrocardiogram had to be present. Unstable angina was
diagnosed when the serum biochemical markers indicative
of myocardial necrosis were within the normal range. The
major end points of the present study were the in-hospital
and 6-month mortality and major adverse cardiovascular
events (MACEs). In-hospital MACEs included death,
stroke, repeat myocardial infarction, ventricular fibrillation,
and cardiac arrest. The 6-month follow-up MACEs included
repeat myocardial infarction, cardiac-related rehospitaliza-
tion, and death. The University of Michigan institutional
review board approved the protocol, and all patients pro-
vided informed consent.
The Statistical Package for Social Sciences, version 15.0
(SPSS, Chicago, Illinois) was used for statistical analysis. A
total of 1,541 patients were stratified into 3 categories ac-
cording to the admission glucose level: ⬎70 mg/dl but
⬍100, 100 to ⬍126 mg/dl, and ⱖ126 mg/dl. The fasting
admission glucose level was also analyzed as a continuous
472 The American Journal of Cardiology (www.AJConline.org)
Table 3
First fasting glucose level and in-hospital outcomes
In-hospital outcome* OR (95% CI)
Fasting Glucose Fasting Glucose
100–125 mg/dl ⱖ126 mg/dl
Total cohort (n ⫽ 1,538)
Mortality 12.68 (1.62–98.93) 24.50 (3.26–184.63)
MACEs 1.56 (0.80–3.04) 3.00 (1.62–5.55)
Diabetes mellitus (n ⫽ 456)
Mortality 1.88 (0.17–21.30) 3.55 (0.45–28.11)
MACEs 1.24 (0.27–5.72) 2.39 (0.69–8.29)
No diabetes mellitus
(n ⫽ 1,081)
Mortality — —
MACEs 1.65 (0.79–3.45) 3.37 (1.51–7.51)
CI ⫽ confidence interval; OR ⫽ odds ratio.
* Adjusted for Global Registry of Acute Coronary Events risk score and
gender.
variable. Univariate analysis included chi-square tests for
comparisons between categorical variables, t tests for con-
tinuous variables, and receiver operating characteristic
curves. Statistical significance was set at p ⬍0.05. Multi-
variate logistic regression analyses were performed for in-
hospital and 6-month mortality and MACEs, adjusting for
gender and Global Registry of Acute Coronary Events study
risk scores. The in-hospital Global Registry of Acute Cor-
onary Events study risk score variables include age, Killip
class, systolic blood pressure, ST-segment deviation, car-
diac arrest, elevated creatinine level, positive cardiac en-
zymes, and heart rate.3,4 The 6-month Global Registry of
Acute Coronary Events study risk scores include age, his-
tory of congestive heart failure, history of myocardial in-
farct, heart rate, systolic blood pressure, initial creatinine
level, elevated cardiac enzymes, and no in-hospital percu-
taneous coronary intervention.5
Results
The clinical characteristics of the 1,541 patients admitted
for an ACS event across the fasting admission glucose
groups are listed in Table 1. Of the 1,541 patients, 631 had
a fasting glucose level of ⬍100 mg/dl, 499 had a fasting
glucose level of 100 to 125 mg/dl, and 411 had a fasting
glucose level of ⱖ126 mg/dl. Thirty-five percent of the
patients were men, and no significant differences in gender
distribution among the 3 glucose groups were observed. The
cohort was predominately white. Of the entire cohort, 29%
had a history of diabetes, and a history of diabetes was
observed most often in those with the greatest fasting glu-
cose levels. An increasing glucose level correlated posi-
tively with age and body mass index, history of hyperten-
sion, and renal insufficiency. The rates of unstable angina
and non–ST-segment elevation myocardial infarction were
similar among the 3 glucose groups; however, ST-segment
elevation myocardial infarction was observed more fre-
quently among those with a fasting glucose level of 100 to
125 mg/dl.
Hospital management was similar for the 3 glucose
groups, with the exception of the medications prescribed at
Table 4
First fasting glucose level and 6-month outcomes
6-mo Outcome* OR (95% CI)
Fasting Glucose Fasting Glucose
100–125 mg/dl ⱖ126 mg/dl
Total cohort (n ⫽ 1,493)
Mortality 2.19 (1.09–4.39) 2.70 (1.37–5.31)
MACEs 1.02 (0.77–1.37) 1.50 (1.10–2.03)
Diabetes mellitus (n ⫽ 436)
Mortality 0.77 (0.16–3.57) 1.85 (0.60–5.72)
MACEs 1.10 (0.56–2.17) 1.10 (0.62–1.95)
No diabetes mellitus (n ⫽ 1,056)
Mortality 3.03 (1.35–6.81) 2.81 (1.07–7.36)
MACEs 0.98 (0.71–1.36) 1.49 (0.96–2.33)
* Adjusted for Global Registry of Acute Coronary Events risk score and
gender.
Abbreviations as in Table 3.
discharge (Table 2). The rates of thrombolytics and revas-
cularization were similar among the 3 glucose groups. The
medications used at admission differed for some medica-
tions but not for all. Patients in the greatest glucose group
had been prescribed ␤ blockers and statins more often
before admission for ACS than the patients with a normal
fasting glucose or a level of 100 to 125 mg/dl. In contrast,
patients in the greatest glucose group were discharged less
often with aspirin or statins compared with the other glucose
groups. The receipt of ␤ blockers at discharge occurred
most often among those with a fasting glucose level of 100
to 125 mg/dl, followed by those in the normoglycemic
group and least often among those with the highest admis-
sion glucose level.
Of the 1,541 patients, 27 died during hospitalization. An
increasing fasting glucose level was associated with an
increased rate of in-hospital mortality, from 0.5% (n ⫽ 2)
for the patients with an admission fasting glucose of ⬎70
but ⬍100 mg/dl to 3.0% (n ⫽ 11) for those with a fasting
glucose of 100 to 125 mg/dl and 3.8% (n ⫽ 14) for those
with a fasting glucose level of ⱖ126 (p ⬍0.001 for trend).
In multivariate models, after adjustment for the Global
Registry of Acute Coronary Events study risk score and
gender, the fasting glucose level at admission was signifi-
cantly associated with in-hospital death (Table 3). For the
total cohort, both the group with a fasting glucose level of
100 to 125 mg/dl and the group with a level of ⱖ126 mg/dl
were at a significantly increased risk of in-hospital death
compared with the group with a level ⬍100 mg/dl. A
similar pattern was observed for the outcome of in-hospital
MACEs, with a trend toward increased risk in those with a
level of 100 to 125 mg/dl and a significantly increased risk
in patients with a fasting glucose level of ⱖ126 mg/dl. A
subgroup analysis, separating patients with known diabetes
and those without known diabetes, demonstrated increased
risk among patients with no known diabetes for in-hospital
MACEs at the greatest glucose level. Among those with
diabetes, a trend toward an increased risk of both in-hospital
mortality and in-hospital MACEs was observed, which did
not reach statistical significance. We were not able to ex-
amine in-hospital mortality in those without diabetes be-
cause no deaths occurred in this subgroup.
 Coronary Artery Disease/Prognostic Value of Glucose Levels
During the 6-month follow-up period, 71 patients died.
As with in-hospital mortality, a positive association was
observed for 6-month mortality and the fasting glucose
level, with a mortality rate of 3.5% (n ⫽ 13) for the nor-
moglycemic group and 6.9% (n ⫽ 25) for the group with a
fasting glucose level of 100 to 125 mg/dl, to 9.0% (n ⫽ 33)
for the group with the greatest glucose level (p ⬍0.001 for
trend). A total of 404 MACEs occurred during the 6-month
follow-up period. The rate of 6-month MACEs was posi-
tively associated with the glucose level, with a rate of 28.8%
(n ⫽ 83) in the normoglycemic group, 32.8% (n ⫽ 97) in
the group with levels of 100 to 125 mg/dl, and 44.1% (n ⫽
113) in the group with the greatest glucose levels (p ⫽ 0.002
for trend).
The fasting glucose level on admission was indepen-
dently associated with the 6-month outcomes (Table 4). For
the total cohort, an increased risk of 6-month mortality was
observed for both groups with glucose levels of ⱖ100 mg/dl
compared with those with normal glucose levels. A similar
pattern was noted for the 6-month MACE outcome that did
not reach statistical significance for patients with impaired
glucose levels but was significant for those with hypergly-
cemia. A similar trend was observed for patients with
known diabetes for both 6-month mortality and 6-month
MACEs. For patients with no known diabetes, both im-
paired glucose and hyperglycemia were independently pre-
dictive of 6-month mortality. No such trend was observed
for 6-month MACEs in relation to impaired glucose; how-
ever, a trend toward an increased risk was observed for
patients whose admission fasting glucose was ⱖ126 mg/dl.
Discussion
In the present study of patients with ACS, we observed
that an elevated fasting admission glucose level was asso-
ciated with adverse events both in-hospital and at the
6-month follow-up point. Furthermore, the risk of adverse
events associated with the fasting glucose level at admission
was often greatest for nondiabetic patients with ACS.
Our results are consistent with previous investigations in
ACS cohorts demonstrating a relation between mortality
and hyperglycemia.6 –12 A meta-analysis of 15 studies, with
limited sample sizes, demonstrated that in-hospital death
was positively associated with the glucose level for both
diabetics and nondiabetics.13 Although our study used an
admission fasting glucose level, most studies of glucose in
relation to ACS have used the admission glucose levels,
which could have included both random and fasting mea-
surements. The admission glucose levels in patients with
ACS reflect a component of the physiologic stress incurred
during ACS, in contrast to the fasting glucose, which might
also reflect a component of glucose tolerance.14 –16 Re-
cently, data have suggested that the fasting admission glu-
cose might be more prognostic than random admission
glucose levels during an ACS hospitalization. Two prospec-
tive studies have indicated that the fasting admission glu-
cose obtained within 24 hours improved the ability to pre-
dict in-hospital mortality and 30-day mortality compared
with random admission glucose levels.9,10 In contrast, a
retrospective study of ⬎16,000 patients with ACS found
that the mean hospital glucose was a better discriminator of
473
mortality than the admission glucose alone, with a greater
risk observed among nondiabetics.17 However, the mean
glucose level, calculated from multiple nonfasting hospital
glucose values during the course of an admission, might be
more difficult than a single fasting admission glucose mea-
surement to use in a clinical setting.
Our results are consistent with previous studies that have
shown an increased incidence of adverse outcomes in pa-
tients with no known diabetes comparable to that seen in
diabetic patients.6,8,14,15,18 –20 The phenomenon might re-
flect an underdiagnosis of diabetes; patients with ACS with
no known diabetes might have experienced elevated glucose
levels, with resulting micro- and macrovascular damage for
years before their ACS event. Furthermore, compared with
those with known diabetes, this subgroup is less likely to be
treated with insulin for hyperglycemia in the hospital during
the ACS event, even in the presence of very high glucose
levels.21 Although the beneficial effect of glucose-lowering
therapy in large prospective trials of patients with ACS has
been admittedly mixed, benefits have been seen in other
critically ill populations.22,23
The present study had several limitations. Patients with
documented ACS who were a part of a large ongoing
registry in 1 academic medical center were used for the
present analysis. This cohort included a wide spectrum of
patients with ACS and, as such, offers a “real life” perspec-
tive of patients with ACS and the related outcomes by
including a heterogeneous study population compared with
randomized control trial study populations. However, the
study design was observational, which is associated with
inherent limitations and potential biases (including selection
bias), and were likely to exist in the present study. Data for
hemoglobin A1c was not available, nor was detailed infor-
mation on oral hypoglycemic agents or insulin treatment.
The use of intravenous fluids containing dextrose was pos-
sible for some subjects and might have affected the fasting
glucose levels; however, we have clinically observed that
normal saline is used preferentially for patients with ACS at
our institution. The multivariate analysis of in-patient death
and MACEs was limited by the numbers of deaths. Cate-
gorizing glucose into 3 groups did not allow us to discrim-
inate between the prognostic significance of more discrete
glucose levels. However, owing to our sample size, we
lacked the power to examine more narrow glucose catego-
ries, particularly when separating the subgroups of patients
with and without diabetes. Also, data for several factors,
including in-hospital outcomes, were determined by chart
review and, as such, might have been subject to documen-
tation errors. We operated under a conservative approach in
which we only assumed an act or outcome to have occurred
if it was specifically documented in the chart. The training
of study staff, in addition to periodic quality reviews, likely
resulted in the reduction of these errors.
A strong association between the admission fasting glu-
cose level and adverse outcomes was observed in our ACS
cohort. Additional research regarding the prognostic signif-
icance of glucose levels, particularly among patients with no
known history of diabetes, is warranted.
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