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

The study population was selected from the Korea Acute Myocardial Infarction Registry between November 2005 and December 2007 and from the registry series Korea Working Group on Myocardial Infarction Registry between January 2008 and September 2010. Data are from a prospective multicenter, online registry in Korea, with 53 hospitals registering consecutive patients with acute myocardial infarction. Between November 2005 and September 2010, 20,344 patients were enrolled in the registries. Data were collected by trained study coordinators using a standardized case report form and protocol. This registry was sponsored by the Korean Society of Cardiology. The institutional review board of all participating centers approved the study protocol (see Appendix). All participating patients provided written informed consent. Inclusion criteria were: consecutive patients 18 years of age or older; ST-segment elevation of 1 mm or more in two or more contiguous leads and new left bundle-branch block with at least one positive cardiac biochemical marker of necrosis; and diagnosis of cardiogenic shock. Exclusion criteria were: unavailable BG level at admission; and mechanical complications such as ventricular septal defect or mitral regurgitation from myocardial infarction. Patients were stratified according to BG levels at admission into group 1 (<7.8 mmol/l; n = 181), group 2 (7.8 to 10.9 mmol/l; n = 215), group 3 (11.0 to 16.5 mmol/l; n = 216) or group 4 (≥16.6 mmol/l; n = 204) (Figure 1). Patients with a previous history of DM treated with insulin, oral antihyperglycemic agents, or lifestyle modification at index hospital admission were classified as patients with DM. The patient flow of the study is shown in Figure 1. Clinical, laboratory, and outcome data were collected using a Web-based reporting system. Additional information was documented by contacting general practitioners and by review of hospital records. The primary outcome was 30-day mortality.

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.

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 [14] 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 [15]. 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 [16]. 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.

Between November 2005 and September 2010, 844 patients presented with STEMI complicated by cardiogenic shock. Of these, 816 (96.7%) had complete admission BG data (Figure 1). The mean admission BG level was 13.2 ± 7.0 mmol/l. Baseline clinical characteristics are presented in Table 1; 239 patients (29.3%) were classified as having DM, including 21 patients treated with insulin. Overall, patients with higher admission BG levels were higher-risk subjects. This group had a higher prevalence of females, DM, low systolic and diastolic blood pressure, anterior wall myocardial infarction, and elevated serum creatinine and TIMI risk score. Treatment during hospitalization is shown in Table 2; 644 (78.9%) underwent primary percutaneous coronary intervention. Similarly, patients with higher admission BG levels had higher use of mechanical ventilation and intra-aortic balloon pumps, and were less likely to receive aspirin, clopidogrel, and statins.

Figure 2 shows the cumulative 30-day mortality of the study population stratified by admission BG level and presence or absence of diabetes. Total 30-day mortality was 32.0%; 30-day mortality in patients with diabetes was 36.0% compared with 30.3% for patients without diabetes (P = 0.115). In the total study population, 30-day mortality rates were higher in patients with higher admission BG levels (20.4% for patients with admission BG level <7.8 mmol/l, 23.3% for 7.8 to 10.9 mmol/l, 39.8% for 11.0 to 16.5 mmol/l, and 43.1% for ≥16.6 mmol/l, P <0.001). Similarly, among nondiabetic patients, 30-day mortality rates were higher in patients with higher admission BG levels (20.0%, 22.6%, 40.1%, and 48.9%, P <0.001). However, diabetic patients showed no significant difference in 30-day mortality according to admission BG level (23.1%, 28.0%, 39.2%, and 38.6%, P = 0.404).

Cox regression analysis was performed to determine predictors of 30-day mortality (Table 3). In nondiabetic patients, independent predictors for the occurrence of 30-day mortality were female, anterior wall myocardial infarction, serum creatinine >1.5 mg/dl, mechanical ventilation support, use of intra-aortic balloon pump, and admission BG level group. In diabetic patients, the independent predictors for the occurrence of 30-day mortality were age ≥75 years, female, and low systolic blood pressure.

Receiver operating characteristic curves for admission BG level, TIMI risk score, GRACE risk score, and the combination of admission BG and TIMI or GRACE score are shown in Figure 3. Among nondiabetic patients, admission BG level and TIMI and GRACE scores predicted 30-day mortality, with c-statistics of 0.652 (95% CI, 0.600 to 0.691) for admission BG level, 0.615 (95% CI, 0.561 to 0.662) for TIMI score, and 0.652 (95% CI, 0.604 to 0.695) for GRACE score. The c-statistics scores increased significantly to 0.685 (95% CI, 0.639 to 0.720, P <0.001) for TIMI and to 0.708 (95% CI 0.664 to 0.742, P <0.001) for GRACE when the admission BG level was added. Additionally, improvements in discrimination were confirmed by the integrated discrimination improvement (0.041 (95% CI, 0.022 to 0.059), P <0.001 for TIMI vs. incorporation of BG into TIMI; and 0.039 (95% CI, 0.021 to 0.057), P <0.001 for GRACE vs. incorporation of BG into GRACE).

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).