Original Article

Diabetes Mellitus and Glucose as Predictors of Mortality in Primary

Coronary Percutaneous Intervention
Renato Budzyn David, Eduardo Dytz Almeida, Larissa Vargas Cruz, Juliana Cañedo Sebben, Ivan Petry Feijó, Karine
Elisa Schwarzer Schmidt, Luísa Martins Avena, Carlos Antonio Mascia Gottschall, Alexandre Schaan de Quadros

Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS - Brazil

Abstract
Background: Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment
elevation myocardial infarction patients, but their relative and individual role remains on debate.
Objective: To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment
elevation myocardial infarction patients submitted to primary coronary percutaneous intervention.
Methods: Prospective cohort study including every ST segment elevation myocardial infarction patient submitted
to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012.
We collected clinical, angiographic and laboratory data during hospital stay, and performed a clinical follow‑up
30 days after the ST segment elevation myocardial infarction. We adjusted the multivariate analysis of the
studied risk factors using the variables from the GRACE score.
Results: Among the 740 patients included, reported diabetes mellitus prevalence was 18%. On the univariate analysis,
both diabetes mellitus and admission blood glucose were predictors of death in 30 days. However, after adjusting for
potential confounders in the multivariate analysis, the diabetes mellitus relative risk was no longer significant (relative risk:
2.41, 95% confidence interval: 0.76 – 7.59; p-value: 0.13), whereas admission blood glucose remained and independent
predictor of death in 30 days (relative risk: 1.05, 95% confidence interval: 1.02 – 1.09; p-value ≤ 0.01).
Conclusion: In ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous
intervention, the admission blood glucose was a more accurate and robust independent predictor of death than the
previous diagnosis of diabetes. This reinforces the important role of inflammation on the outcomes of this group of
patients. (Arq Bras Cardiol. 2014; 103(4):323-329)
Keywords: Diabetes Mellitus; Blood Glucose; Biological Markers; Myocardial Infarction; Percutaneous Coronary
Intervention.

Introduction outcomes after STEMI are scarce and do not reflect the current
practice of interventional cardiology18-20.
Diabetes mellitus (DM) is an important risk factor for
mortality in patients with ST-segment elevation myocardial The pathophysiological characteristics of hyperglycemia
infarction (STEMI)1-3. In addition, high blood glucose levels in STEMI patients are distinct from those observed in DM
on admission are directly related to short-term mortality after patients in stable clinical conditions21. The most recent
STEMI4-9, regardless of previous diagnosis of DM10-14 or the guidelines of the European Society of Cardiology reveal some
reperfusion therapy used15. Primary percutaneous coronary controversies in the acute management of blood glucose
intervention (PPCI) is currently the reperfusion therapy of levels in STEMI patients and indicate the need for further
assessment of this variable during contemporary medical
choice in STEMI patients when performed in a timely manner
practice22. The present study aimed to evaluate the effect of
and by experienced cardiologists16,17. However, previous
DM and admission hyperglycemia on short-term mortality
studies on the effect of admission glucose levels on clinical
in STEMI patients subjected to PPCI.

Methods
Mailing Address: Alexandre Schaan de Quadros •
Avenida Princesa Isabel, 370, Santana. Postal Code 90620-000, Porto Alegre,
Rio Grande do Sul, Brazil Experimental design
E-mail: [email protected]; [email protected]
Manuscript received February 12, 2014; revised manuscript May 06, 2014;
This unicentric prospective cohort study evaluated
accepted May 09, 2014. all STEMI patients subjected to PPCI at our institution
between December 2010 and May 2012. Our hospital
DOI: 10.5935/abc.20140130 is a high-volume tertiary referral center for interventional

323
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Blood Glucose Levels and Mortality after Primary Angioplasty

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cardiology. It performs approximately 2,500 percutaneous Statistical analysis

coronary interventions (PCI) per year, and PPCI is the routine Statistical analysis was performed using the Statistical
reperfusion strategy for STEMI patients. The Research Ethics Package for the Social Sciences (SPSS) software version
Committee of this institution reviewed the present study, and 16.0 (SPSS, Inc., Chicago, Illinois). The study power was
all patients enrolled signed a free informed consent form. calculated using the comparison of proportions. Considering
The authors are solely responsible for the design and conduct the sample size, the power to detect a difference in the
of the study, including the analyses, design, manuscript 30‑day outcome of death between patients with and
revisions, and approval of the final manuscript. No external without DM was 82% using Fisher’s exact test. Categorical
funding was provided to support this study. variables were reported as frequency and percentage.
Continuous data were presented as the mean and standard
Patients deviation. Variables were considered normal on the basis of
STEMI patients hospitalized in our institution and the values of central tendency, kurtosis, and skewness in the
referred to PPCI by the attending physician were included frequency histograms, in addition to statistical analysis used
in the study. For most patients, this was their first contact in previous studies. The chi-square or Fisher’s exact test
with our institution. STEMI was defined as chest pain at rest was used for comparisons between categorical variables.
for > 30 min, associated with (1) ST-segment elevation of The t test was used for comparisons between continuous
>1 mm in ≥2 contiguous electrocardiographic leads or variables. A p value of <0.05 was considered significant.
(2) new left bundle branch block. Exclusion criteria were Multivariate analysis with stepwise and backward logistic
as follows: chest pain for >12 h, age of <18 years, and regression models was used to identify independent predictors
patient refusal to enroll in the study. of cardiovascular mortality 30 days after hospital discharge.
PPCI was performed as recommended in the literature17. Initially, a model including only DM and the GRACE score was
Upon admission, all patients were treated with 300 mg adopted to assess the contribution of DM in the rate of events,
of acetylsalicylic acid and 300–600 mg of clopidogrel. corrected by a robust score and including comorbidities and
Unfractionated heparin (60–100 U/kg) was administered clinical variables. Subsequently, a second multivariate analysis
before PPCI. The technical aspects of the procedure, such was performed, including DM, GRACE score26,27, and other
as type and number of stents, use of adjunct devices, and variables with statistical significance. The dependent variables
administration of glycoprotein IIb/IIIa inhibitors, were decided included in this model were as follows: GRACE score, post-PCI
by the cardiologist responsible for PPCI. TIMI flow grade 3, DM, delta T, blood glucose, and cholesterol.
Blood samples were collected in the emergency room and
analyzed in the hemodynamics room. Results
Clinical outcomes and patient follow-up During the study period, 740 patients underwent PPCI
within the first 12 h after STEMI. DM was present in 134 patients
Patients were monitored during hospitalization and
(18%). Table 1 compares the basic characteristics of patients
by phone contact 1 month after hospital discharge.
with and without DM. DM patients were older, predominantly
Coronary flow before and after the procedure was
women, with a higher frequency of hypertension, dyslipidemia,
assessed according to the guidelines established by
and previous angina. In DM Patients, smoking was less
the Thrombolysis in Myocardial Infarction (TIMI) study
common, whereas chronic use of aspirin was more frequent.
group 23. Myocardial perfusion was evaluated using the
Approximately 40% infarctions occurred on anterior artery
myocardial blush grade24. Stent thrombosis was defined
walls, with no significant difference between the groups with
according to the criteria established by the Academic
and without DM. Patients with DM had an increased body mass
Research Consortium25. Delta T was defined as the time
index and waist circumference compared with those without.
between the onset of chest pain and hospital admission.
Door-to-balloon time was defined as the time between DM patients had higher glucose levels on admission and
hospital admission and the first balloon inflation procedure lower plasma cholesterol levels.
in the artery associated with acute myocardial infarction In general, the angiographic profile of patients with and
(AMI). The definition of DM was based on patients’ without DM was similar. However, DM patients exhibited
information and use of hypoglycemic therapy. a lower Blush 3 score after the procedure (57% vs. 69%;
With regard to follow-up, major adverse cardiac events p < 0.01). Most of the stents implanted (99.3%) were of
(MACE) were defined as the combination of death from the conventional type.
all causes, new AMI, or stroke. New AMI was defined During hospital follow-up, the rates of severe arrhythmia
as recurrent chest pain with an elevation of serum or cardiac arrest (11.5% vs. 7.7%; p = 0.15) and stent
biomarkers, following an initial decline in the natural thrombosis (3.1% vs. 3%; p = 0.96) in patients with DM
curve, with ST-segment elevation or new Q waves. Urgent were similar to those in patients without DM. However,
revascularization was defined as both an unplanned the occurrence of acute renal failure (8.5% vs. 2.5%;
revascularization procedure within 30 days after STEMI, p < 0.01), the need for mechanical ventilation (11.5% vs.
and PCI or a coronary artery bypass grafting procedure for 6.5%; p = 0.04), and the development of congestive heart
the treatment of recurrent ischemia. failure (13.7% vs. 6.5%; p = 0.01) were more frequent

Arq Bras Cardiol. 2014; 103(4):323-329 324

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Table 1 – Clinical profile of patients (n = 740) according to the presence or absence of diabetes mellitus

DM Absence of DM
Characteristic p value
(N = 134) (N = 606)
Age (years) 63 ± 11 60 ± 12 < 0.01
Female (%) 38 29 0.04
Caucasian (%) 90 87 0.43
Hypertension (%) 80 61 < 0.01
Dyslipidemia (%) 47 30 < 0.01
Current smoking (%) 28 45 < 0.01
Family history (%) 26 33 0.13
Medical history
AMI (%) 27 20 0.06
CABG (%) 5 2 0.19
CRF (%) 3 2 0.63
Angina (%) 48 36 0.01
Daily use of ASA (%) 41 23 < 0.01
ECC, mL/min/1.73 m 2
86 ± 37 87 ± 31 0.81
Total cholesterol (mg/dL) 192 ± 52 204 ± 57 0.02
BMI, (kg/m )
2
27.6 ± 4.3 26.8 ± 4.1 0.05
AC (cm) 96 ± 14 93 ± 15 0.05
SBP (mmHg) 136 ± 32 135 ± 29 0.86
Delta T (hours) 5.2 ± 5.3 4.6 ± 4.3 0.12
DBT (hours) 1.7 ± 1.3 1.56 ± 1.3 0.30
Admission glucose levels (mg/dL) 253 ± 124 143 ± 51 < 0.01
AMI: acute myocardial infarction; CABG: coronary artery bypass grafting procedure; CRF: chronic renal failure; ASA: acetylsalicylic acid; ECC: endogenous creatinine
clearance; BMI: body mass index; AC: abdominal circumference; SBP: systolic blood pressure; DBT: door-to-balloon time; DM: diabetes mellitus.

in DM patients. Figure 1 shows a 30-day follow-up as a Discussion

function of DM. The incidence of MACE (20.1 vs. 11.6; The present study confirms the increased risk of adverse
p < 0.01) and death (16.4% vs. 7.3%; p < 0.01) were events for diabetic patients with STEMI subjected to PPCI.
higher in patients with DM than in those without. Furthermore, it showed that DM is a predictor of short‑term
The multivariate analysis for the 30-day outcome of death events when corrected for the multiple comorbidities
was initially performed using DM and GRACE score variables, represented in the GRACE risk score26,27. However, DM lost its
both of which proved to be predictors of this outcome: statistical significance when other variables, e.g., admission
GRACE risk score [relative risk (RR): 1.048, 95% confidence glucose levels, were added to the multivariate model used
interval (CI): 1.037–1.059; p < 0.01] and DM (RR: 1.926, for predicting 30-day mortality. These results demonstrate
95% CI: 1.016–3.650; p = 0.04). The complete model, the importance of hyperglycemia on admission as a risk
including other variables and admission glucose levels, is factor for short-term events in this context, and suggest
shown in Table 2. We observed that when considering the that a significant proportion of the risk represented by DM
variables representing the baseline risk of the patient as a is mediated by admission hyperglycemia, which is more
result of PPCI and admission glucose levels, DM lost statistical frequent and pronounced in patients with DM compared
significance. Nevertheless, admission glucose levels were an with those without DM.
important predictor of the 30-day outcome of death because Hyperglycemia in DM patients is caused by resistance
an increase of 10 mg/dL in the glucose levels was observed for to insulin and decreased insulin production in pancreatic
every 5% increase in RR events (RR: 1.05, 95% CI: 1.02–1.09; cells, whereas stress hyperglycemia during AMI and in other
p < 0.01). The cutoff glucose level for the optimal prediction serious acute diseases is caused by a complex mechanism
of the primary outcome was evaluated using the receiver of secretion of hormones, including adrenaline, glucagon,
operating characteristic curve, which yielded a glucose level growth hormone, and cytokines. In addition to being a marker
of 159 mg/dL, a sensitivity of 63%, a specificity of 68%, and of the severity of clinical conditions, myocardial damage
an area under the curve of 0.65 (95% CI: 0.61–0.69). from stress hyperglycemia may be due to adverse effects

325 Arq Bras Cardiol. 2014; 103(4):323-329

 David et al.
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Original Article

25%
p < 0.01 Patients with DM
20.1 Patients without DM
20% p < 0.01
16.4
15%
11.6
p = 0.16
10% p = 0.94
7.3 7.3
6.2 6.3
5% 3.8

0%
MACE Deaths New AMI Revasc

Figure 1 – Clinical outcomes during a 30-day follow-up (n = 740) as a function of DM. MACE:major adverse cardiac events; new AMI: acute myocardial infarction;
Revasc: new revascularization.

Table 2 – Multiple logistic regression analysis for 30-day mortality

Predictor Relative risk 95% CI p value

GRACE score 1.04 1.03 – 1.06 < 0.01
Post-PCI TIMI flow grade 3 0.30 0.12 – 0.71 < 0.01
DM 2.41 0.77 – 7.60 0.13
Delta T 1.08 1.02 – 1.15 < 0.01
Admission blood glucose levels* 1.05 1.02 – 1.09 < 0.01
Total cholesterol 0.99 0.98 – 1.00 0.05
*Admission glucose levels were included in the model in increments of 10 mg/dL.
PCI: percutaneous coronary intervention; Diabetes mellitus: DM

including increased oxidative stress, platelet activation, and the results of previous studies34. Even with a TIMI flow grade
endothelial dysfunction, leading to increased infarct size21. 3 after PPCI, DM patients exhibit less complete resolution of
Previous studies have shown that hyperglycemia induces an the ST segment after stent implantation, which also indicates
inflammatory response during AMI28 and that its resolution impaired microvascular flow35. These results corroborate the
can restore this response29. Two cohort studies of AMI patients worse cardiovascular outcomes that DM patients exhibit
(with and without ST-segment elevation) demonstrated that after STEMI.
admission hyperglycemia was an independent predictor of Recent studies have suggested that DM is primarily
in-hospital mortality30,31 but was not significant for long-term associated with worse long-term outcomes in STEMI
mortality30. In addition, admission hyperglycemia had distinct patients, whereas the increased cardiovascular risk was
effects on mortality when patients were subdivided into age primarily due to hyperglycemia. Ishihara et al 18 and
groups31. The analysis of the CARDINAL study indicated Hoebers et al 19 demonstrated that hyperglycemia, but
that the decreased blood glucose levels in the first 24 h after not DM, is associated with short-term adverse events in
infarction was associated with decreased 30-day mortality in STEMI patients subjected to PCI. Ergelen et al 20 analyzed
patients without DM32. the clinical outcome of STEMI patients as a function
DM patients have impaired microvascular structure of DM and blood glucose levels: DM with admission
and diffuse endothelial dysfunction, which contributes to hyperglycemia, DM without admission hyperglycemia,
decreased blood perfusion, particularly in the context of absence of DM with admission hyperglycemia, and
acute hypoperfusion, such as STEMI33. In the present study, absence of DM without admission hyperglycemia. It was
the percentage of patients who achieved a Blush 3 score after observed that patients without DM and with admission
the procedure was lower in the group with DM, corroborating hyperglycemia had a higher risk of in-hospital mortality,

Arq Bras Cardiol. 2014; 103(4):323-329 326

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whereas DM patients with admission hyperglycemia had this limitation has occurred in other observational studies on
the worst long-term outcomes. These results agree with AMI patients subjected to PPCI.
those of Kosiborod et al7 who, in a large study of AMI
patients, showed that the risk of mortality of patients with
admission hyperglycemia was higher for those without a Conclusion
DM history, compared with DM patients. This effect is This contemporary analysis with consecutive patients,
not restricted to STEMI cases because patients admitted representative of the clinical practice in a tertiary interventional
to intensive care units with severe acute illnesses and cardiology hospital, corroborates the increased risk for DM
admission hyperglycemia had worse clinical outcomes patients subjected to primary angioplasty. It demonstrates
compared with those having lower glucose levels36. the important prognostic role of admission hyperglycemia
Our study reinforces the results reported above and in predicting short-term adverse cardiovascular events.
demonstrates that the unfavorable prognostic role of Furthermore, the latter variable does not depend on other
hyperglycemia in short-term adverse events is more relevant comorbidities or clinical diagnoses, including the diagnosis
and independent than the role of DM 18. An important of DM, and is more important than DM.
advantage of the present study is the inclusion of unselected
and consecutive patients, representative of real-world clinical Author contributions
practice. The percentage of DM patients was 18%, which was
similar to that reported in other studies (17–21%)2,34,37. Conception and design of the research: David RB, Sebben
JC, Gottschall CAM, Quadros AS; Acquisition of data: David
Limitations RB, Almeida ED, Sebben JC, Feijó IP, Schmidt KES, Avena
LM; Analysis and interpretation of the data AND Writing of
One limitation of the present study involves the lack of data
the manuscript: David RB, Almeida ED, Cruz LV, Quadros AS;
on glycosylated hemoglobin (HbA1c). Approximately 50% of
Statistical analysis: David RB, Quadros AS; Critical revision of
STEMI patients experience changes in glucose metabolism38,
the manuscript for intellectual content: David RB, Almeida
and HbA1c can be a diagnostic criterion of DM39. Moreover,
ED, Cruz LV, Sebben JC, Feijó IP, Schmidt KES, Avena LM,
it was demonstrated that the prognostic role of admission
Gottschall CAM, Quadros AS.
hyperglycemia is more important than increased HbA1c
levels40, and that HbA1c assumes greater significance in
predicting long-term events instead of predicting short-term Potential Conflict of Interest
events9,11. The criteria used for the diagnosis of DM (reported No potential conflict of interest relevant to this article
by the patient) may have underestimated the number of was reported.
DM patients. However, it is important to highlight that the
percentage of DM patients found herein was similar to that in
previous studies, and the blood glucose levels was significantly Sources of Funding
higher in patients with DM than in those without. Moreover, There were no external funding sources for this study.
the assessment of ventricular function during hospitalization
was performed by the medical staff, and the study protocol
did not include the routine and prospective collection of such Study Association
data. The large amount of missing data on ventricular function This study is not associated with any thesis or
(>25%) prevented the accurate analysis of this variable, and dissertation work.

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