Prognostic value of admission blood glucose level in patients with and without diabetes mellitus who sustain ST segment elevation myocardial infarction complicated by cardiogenic shock
© Yang et al.; licensee BioMed Central Ltd. 2013
Received: 22 March 2013
Accepted: 20 August 2013
Published: 3 October 2013
Admission blood glucose (BG) level is a predictor of mortality in patients with ST-segment elevation myocardial infarction (STEMI). However, limited data are available relating admission BG to mortality in patients with STEMI complicated by cardiogenic shock, and it is not known whether diabetic status has an independent effect on this relationship.
Between November 2005 and September 2010, 816 STEMI patients with cardiogenic shock were enrolled in a nationwide, prospective, multi-center registry; 239 (29.3%) had diabetes mellitus (DM). Patients were categorized according to BG levels at admission: <7.8, 7.8–10.9, 11.0–16.5 and ≥ 16.6 mmol/L. The primary outcome was 30-day mortality. The added values of BG to the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) scores were assessed by receiver operating characteristic curves and integrated discrimination improvement analyses.
Thirty-day mortality was higher in patients with higher admission BG (20.4%, 23.3%, 39.8%, and 43.1% p < 0.001). Among non-diabetic patients, 30-day mortality was predicted by TIMI scores with a c-statistic of 0.615 (95% confidence interval [CI], 0.561–0.662) and GRACE scores with a c-statistic of 0.652 (95% CI, 0.604–0.695). Incorporation of admission BG increased the c-statistic for TIMI score to 0.685 (95% CI, 0.639–0.720, p < 0.001) and GRACE score to 0.708 (95% CI 0.664–0.742, p < 0.001). Additional predictive values for BG were not observed for diabetes. Integrated discrimination improvements (TIMI vs. additional BG and GRACE vs. additional BG) were 0.041 (p < 0.001) and 0.039 (p < 0.001) in non-diabetic patients.
In a cohort of patients with STEMI complicated by cardiogenic shock, admission BG was an independent predictor of increased risk of mortality only among patients without DM.
Cardiogenic shock complicating ST-segment elevation myocardial infarction (STEMI) remains a leading cause of death with a hospital mortality rate approaching 50% . The identification of risk predictors of mortality is important for tailoring more aggressive therapies that can improve survival in patients with cardiogenic shock . Admission blood glucose (BG) level is an independent predictor of mortality in patients with STEMI, regardless of diabetic status and the occurrence of the no-reflow phenomenon [3–6]. In addition, hyperglycemia is associated with a higher level of cardiac necrosis markers . Elevated BG level is proposed to be caused by a complex interplay between counteracting regulatory hormones such as cortisol, glucagon, growth hormone, and cytokines [8, 9]. In heterogeneous populations of critically ill patients, hyperglycemia is independently associated with mortality [10, 11]. However, limited data are available for stratified analysis of the presence or absence of diabetes mellitus (DM) in patients with cardiogenic shock. We therefore investigated the impact of admission BG level on 30-day mortality among patients with STEMI complicated by cardiogenic shock. Furthermore, to improve the effectiveness of admission BG level as a marker for short-term mortality, we evaluated the additive predictive value of BG level at admission to the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores according to the presence or absence of DM.
Materials and methods
A clinical diagnosis of cardiogenic shock was made if all of the following were present: systolic blood pressure persistently lower than 90 mmHg or vasopressors required to maintain a blood pressure greater than 90 mmHg; signs of hypoperfusion (for example, urine output less than 30 ml/hour or cold/diaphoretic extremities or an altered mental status); and clinical evidence of left ventricular filling pressure (for example, pulmonary congestion on physical examination or chest X-ray scan). Vasopressor use was defined as use of dopamine, norepinephrine, and epinephrine regardless of their minimal dose. Thirty-day mortality was defined as any death during or after the procedure within 30 days and was considered to be of cardiac origin unless documentation indicated another cause. Admission BG was obtained by arterial or venous samples in an emergency room and measured with an arterial blood gas analyzer or laboratory analyzers in routine use at each hospital.
Calculation of the TIMI and GRACE risk scores
Clinical scoring included the TIMI and GRACE risk scores for all enrolled patients. Full details of the design and methods of the TIMI and GRACE risk scores have been previously published [12, 13]. The TIMI risk score consists of age, prior angina, diabetes, hypertension, systolic blood pressure <100 mmHg, heart rate >100 beats/minute, Killip class II to IV, weight <67 kg, anterior ST-segment elevation or left bundle branch block on electrocardiogram, and time to thrombolytics >4 hours. The GRACE risk score consists of age, heart rate, systolic blood pressure, serum creatinine level at presentation, Killip class, cardiac arrest at admission, ST-segment deviation on electrocardiogram, and elevated cardiac enzymes. Values for these variables were entered into the GRACE risk calculator  to obtain estimates of the cumulative risks of all-cause mortality.
All continuous values were presented as the mean with standard deviation or the median with interquartile range. Categorical variables were presented as frequencies and percentages. Comparisons between continuous variables were tested using analysis of variance or the Kruskal–Wallis test, as appropriate. Categorical data were tested using the chi-squared test or Fisher’s exact test, as appropriate. Event-free survival was estimated by the Kaplan–Meier method and compared using the log-rank test within 30 days. Covariates statistically significant on univariate analysis (P <0.05) and those clinically relevant were considered candidate variables in multivariate models. Cox proportional-hazards models were adjusted by covariates as follows: age >75 years, sex, body weight <67 kg, systolic blood pressure (per 10 mmHg increase), anterior wall infarction on electrocardiography, serum creatinine >1.5 mg/dl, mechanical ventilation, intra-aortic balloon pump and admission BG level (group). Binary logistic regression was employed to measure the predictive probabilities of the combination of BG level and established risk score models for 30-day mortality. Comparisons among the various risk models of the predictive accuracy with the c-statistic, a measure of the area under the receiver-operator characteristic curve, were carried out using the procedure proposed by DeLong and colleagues according to the presence or absence of DM . The 95% confidence intervals (CIs) were calculated using the bootstrapping procedure (n = 1,000 bootstrap samples) for area under the receiver-operator characteristic curve estimations and the differences between model areas under the receiver-operator characteristic curve. Furthermore, we estimated the integrated discrimination improvement to examine whether predictions based on the TIMI and GRACE risk models without admission BG level were significantly improved after inclusion of the admission BG level as a continuous parameter . Statistical analyses were performed with SAS 9.2 (SAS Institute Inc., Cary, NC, USA) or Stata version 11.0 (StataCorp, College Station, TX, USA). All tests were two tailed and P <0.05 was considered statistically significant.
Baseline and procedural characteristics
Baseline patient characteristics
Serum glucose level on admission
7.8 to 10.9 mmol/l
11.0 to 16.5 mmol/l
(group 1, n= 181)
(group 2, n= 215)
(group 3, n= 216)
(group 4, n= 204)
67.0 (56.0 to 76.0)
67.0 (56.0 to 76.0)
68.0 (56.0 to 76.0)
67.0 (58.0 to 75.0)
Body weight (kg)
61.0 (53.0 to 70.0)
61.0 (55.0 to 69.5)
61.0 (55.0 to 69.3)
61.5 (55.0 to 69.0)
Oral hypoglycemic agent
Life style modification
Family history of CAD
Systolic blood pressure (mmHg)
90 (75 to 120)
80 (70 to 104)
80 (60 to 110)
75 (50 to 100)
Diastolic blood pressure (mmHg)
60 (50 to 71)
51 (40 to 70)
50 (40 to 70)
50 (34 to 60)
Heart rate (beats/minute)
74 (55 to 95)
66 (46 to 89)
68 (48 to 100)
68 (37 to 104)
Infarct location on electrocardiogram
Anterior or LBBB
Left ventricular ejection fraction
46.5 (39.0 to 57.0)
47.0 (39.0 to 56.0)
46.0 (36.0 to 57.0)
44.0 (35.0 to 52.5)
Serum creatinine (mg/dl)
1.1 (0.9 to 1.4)
1.1 (1.0 to 1.4)
1.2 (1.0 to 1.5)
1.3 (1.1 to 1.6)
TIMI risk score
8 (6 to 10)
8 (6 to 10)
8 (7 to 10)
8 (7 to 10)
GRACE risk score
227.0 (205.0 to 245.0)
228.0 (208.0 to 248.0)
230.5 (210.0 to 250.3)
230.0 (216.8 to 248.5)
Treatment during hospitalization
Serum glucose level on admission
7.8 to 10.9 mmol/l
11.0 to 16.5 mmol/l
(group 1, n= 181)
(group 2, n= 215)
(group 3, n= 216)
(group 4, n= 204)
Low molecular weight heparin
Glycoprotein IIb/IIIa inhibitor
Angiotensin receptor blocker
Intra-aortic balloon pump
Predictors of 30-day mortality in patients with and without diabetes
Significant predictors of 30-day mortality with and without diabetes
Nondiabetes (n= 577)
Diabetes (n= 239)
Hazard ratioa(97.5% CI)
Adjusted P value
Hazard ratioa(97.5% CI)
Adjusted P value
Age ≥75 years
1.10 (0.74 to 1.56)
1.80 (1.00 to 3.23)
1.93 (1.29 to 2.90)
1.97 (1.07 to 3.62)
Body weight <67 kg
1.03 (0.67 to 1.60)
0.76 (0.39 to 1.46)
Systolic blood pressure, per 10 mmHg increase
0.96 (0.93 to 1.01)
0.94 (0.87 to 0.99)
Anterior wall infarction on electrocardiography
1.94 (1.34 to 2.82)
1.47 (0.85 to 2.57)
Wide QRS tachycardia on admission
1.55 (0.95 to 2.53)
1.64 (0.69 to 3.91)
Serum creatinine >1.5 mg/dl
1.56 (1.09 to 2.25)
1.61 (0.92 to 2.81)
2.36 (1.59 to 3.48)
1.81 (0.99 to 3.32)
Intra-aortic balloon pump
1.54 (1.06 to 2.23)
1.04 (0.57 to 1.87)
Admission glucose level (vs. group 1)
Group 2 (7.8 to 10.9 mmol/l)
1.19 (0.69 to 2.06)
2.40 (0.62 to 9.31)
Group 3 (11.0 to 16.5 mmol/l)
1.76 (1.06 to 2.94)
1.74 (0.59 to 5.18)
Group 4 (≥16.6 mmol/l)
1.72 (1.02 to 3.00)
1.74 (0.60 to 5.04)
Additive prognostic value of admission glucose level to TIMI and GRACE scores
In contrast, in diabetic patients the admission BG level performed poorly, with a c-statistic of 0.581 (95% CI, 0.513 to 0.651), while the GRACE risk score predicted the occurrence of 30-day mortality with a c-statistic of 0.720 (95% CI, 0.661 to 0.776) (glucose vs. GRACE, P = 0.011). Performances were not improved by the addition of admission BG level to TIMI and GRACE risk score with a nonsignificant increase in the c-statistic of 0.06 for TIMI (P = 0.585) and 0.08 for GRACE score (P = 0.450). Furthermore, significant improvements in discrimination were not observed with the integrated discrimination improvement (0.012 (95% CI, 0.003 to 0.027), P = 0.104 for TIMI vs. incorporation of BG into the TIMI; or 0.014 (95% CI, 0.002 to 0.031), P = 0.084 for GRACE vs. incorporation of BG into GRACE).
We investigated the impact of admission BG level on 30-day mortality and evaluated the additional predictive value of admission BG to the TIMI and GRACE risk scores among patients with STEMI complicated by cardiogenic shock stratified by the presence or absence of DM. Subjects were enrolled from a nationwide, prospective, multicenter registry in Korea. The major findings of this study were that the 30-day mortality rates were higher in patients with higher admission BG levels in nondiabetic patients but not in diabetic patients, and that the admission BG level had an additional predictive value to TIMI and GRACE risk score models in nondiabetic patients but not in diabetic patients.
Acute hyperglycemia on admission and during hospital stay is associated with adverse outcome in patients with acute myocardial infarction regardless of diabetic status [7, 9, 17, 18]. In cardiogenic shock, gluconeogenesis from acute stress could be more prominent. In our study, the mean admission BG level (13.2 mmol/l) was considerably higher than a previous study of STEMI patients with mainly no hemodynamic compromise (7.8 mmol/l). In patients with STEMI complicated by cardiogenic shock, our study found that higher BG levels at admission were associated with higher mortality in the nondiabetic population but not the diabetic population. Similarly, a recent study failed to find a significant relationship between hyperglycemia and mortality in diabetic patients with acute myocardial infarction . In addition, Ishihara and colleagues described a different relationship between admission BG and in-hospital mortality in nondiabetic and diabetic patients, and a hyperglycemia-associated risk that was more obvious in nondiabetic patients than in patients with diabetes . In a heterogeneous population of critically ill patients, mean BG is related to ICU mortality in the nondiabetic cohort but not in the diabetic cohort . These findings suggest that the toxic effect of hyperglycemia on short-term mortality may be less in known diabetic patients. One possible explanation is that the definition and severity of stress hyperglycemia is difficult in diabetic patients because they are more likely to receive insulin or oral hypoglycemic agents before admission for myocardial infarction . These treatments might mitigate the toxic effects of stress hyperglycemia and could disturb the BG level proportionate to the increase in acute stress in diabetic patients. Another possible explanation is that diabetes patients may develop a resistance to hyperglycemia, and a moderate or severe degree of hyperglycemia and glycemic variability that might exert toxicity in a patient without diabetes may be well tolerated in a patient with diabetes .
Identifying high-risk individuals with STEMI complicated by cardiogenic shock remains a challenge. The most widespread tool is the GRACE risk score, which was developed from a large unselected population of patients with all forms of acute coronary syndrome . The TIMI risk score for STEMI is a simple alternative, derived from patients treated with fibrinolytics [12, 23]. Although recent studies suggested variable risk-prediction models for cardiogenic shock, a robust risk model applicable to cardiogenic shock with wide range of mortality rates has not been developed [24, 25]. In our study, incorporation of the admission BG level to the widely accepted TIMI and GRACE risk scores improved its predictive values. Moreover, admission BG level alone was comparable with the TIMI and GRACE risk scores for short-term mortality in nondiabetic patients. Accordingly, an addition of admission BG level to existing risk models could be helpful for developing a new risk model in cardiogenic shock and could improve initial bedside risk stratification.
Our study has several limitations. DM was defined as known diabetic status on admission. Many STEMI patients are known to have undetected DM, and they would not have been excluded in our study [7, 17]. Major weakness of this study is the lack of identification data to distinguish nondiabetes from undetected diabetes. There is therefore no way to discern differential impact on mortality between true nondiabetes and undetected diabetes. We did not routinely measure glycosylated hemoglobin or test for diabetes during admission. Another limitation might be that although admission BG will be responsive to the acute stress associated with a STEMI, many other factors such as prior meals or diurnal variation can contribute to the variability of admission BG levels. Association of the higher admission BG with higher mortality within 30 days might continue in nondiabetic patients. However, the mechanism of this finding is unclear. In addition, we could not identify the impact of BG lowering therapy on mortality because data on BG levels during the course of hospitalization and therapeutic BG targets were not available in our registries. The initial treatment strategy on presentation of a high BG level was left to the operator’s discretion. Large-scale, randomized trials are needed to investigate a relationship between BG lowering therapy and mortality among patients with STEMI complicated by cardiogenic shock. Lastly, the low 30-day mortality of 32.0% in our trial might suggest that our investigation included a relatively high percentage of patients with mild or moderately severe cardiogenic shock. In fact, only 33% of the patients needed mechanical ventilation and 26% underwent insertion of an intra-aortic balloon pump.
In STEMI complicated by cardiogenic shock, the admission BG level was independently associated with increased risk of 30-day mortality and had an additional predictive value for established risk score models in nondiabetic patients but not in diabetic patients.
In nondiabetic patients with STEMI complicated by cardiogenic shock, 30-day mortality rates were higher in patients with higher admission BG levels.
In diabetic patients with STEMI complicated by cardiogenic shock, there is no significant difference in 30-day mortality according to admission BG level.
In a cohort of patients with STEMI complicated by cardiogenic shock, the admission BG level had an additional predictive value to TIMI and GRACE risk score models in nondiabetic patients but not in diabetic patients.
All institutional review boards that approved the study include Samsung Medical Center, Seoul National University Hospital, Gachon University Gil Hospital, Pusan National University Hospital, Chungnam National University Hospital, Chonbuk National University Hospital, Dong-A University Medical Center, Korea University Anam Hospital, Kosin University Gospel Hospital, Eulji Medical Center, Kyungpook National University Hospital, Inje University Busan Paik Hospital, Yeungnam University Medical Center, Korea University Guro Hospital, Seoul National University Bundang Hospital, Gyeongsang National University Hospital, Ewha Womans University Mokdong Hospital, Chonnam National University Hospital, Soon Chun Hyang University Hospital, Buncheon, Kyung Hee University Hospital, Wonkwang University Hospital, Konyang University Hospital, Wonju Christian Hospital, Hallym University Sacred Heart Hospital, Dankook University Hospital, Konkuk University Medical Center, Ulsan University Hospital, Daegu Catholic University Medical Center, Soon Chun Hyang University Hospital, Cheonan, Soon Chun Hyang University Hospital, Seoul, Chosun University Hospital, The Catholic University of Korea, Uijeongbu St. Mary’s Hospital, Inje University Sanggye Paik Hospital, Kangdong Sacred Heart Hospital, Chungbuk National University Hospital, Hanyang University Guri Hospital, Kyung Hee University Hospital at Gangdong, Korea University Ansan Hospital, St. Carollo Hospital, The Catholic Univerity of Korea, Daejeon St. Mary’s Hospital, Presbyterian Medical Center, Veterans Hospital, Dongguk University Ilsan Hospital, Chung-Ang University Hospital, Daejeon Sun Hospital, Jeju National University Hospital, Dongguk University Gyengju Hospital, Inje University Haeundae Paik Hospital, The Catholic University of Korea, St. Paul’s Hospital, SM Christianity Hospital, Kangwon National University Hospital, Best Hanseo Hospital, and Keimyung University Dongsan Medical Center.
Global registry of acute coronary events
ST-segment elevation myocardial infarction
Thrombolysis in myocardial infarction.
The authors appreciate the excellent statistical support of Seonwoo Kim, PhD, and Joonghyun Ahn, MS, at Samsung Biomedical Research Institute.
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