| The finding of abnormally elevated blood glucose is common amongpatients with acute myocardial infarction (AMI). Although several studieshave shown that high blood glucose levels on admission are associated withincreased mortality, the relationship is not well defined. Because of limitedsample sizes, previous studies only evaluated the association betweenglucose level and mortality in patients with very high blood glucose,instead of across the full spectrum of glucose values. Some previousstudies were not undertaken to assess the association between acutehyperglycemia and adverse outcome after AMI in the contemporarymanagement era. Although recommendations of strict glucose control inthe guidelines of the management of patients with ST-ElevationMyocardial Infarction (STEMI) has been made for all hospitalized patients,glucose measurement is not included in the list of AMI risk factors, and nospecific therapeutic target in glucose control was recommended in currentAMI guidelines. The relative lack of guidance concerning the riskstratification and management of AMI patients with elevated glucose mayreflect the fact that many aspects of the relationship between glucose levelsand mortality in AMI patients have not been adequately defined. Patientswith known history of diabetes mellitus (DM) have a higher risk ofadverse cardiovascular events after AMI than those non-diabetic patients.However, the limitation using diabetes history for risk stratification afterAMI is obvious. Little is known about the prognostic impact of theinteraction of acute hyperglycemia and diabetes history in Chinese patients.Whether diabetes history remains useful in AMI risk assessment afteraccounting for admission glucose levels is unclear. To address these gapsin knowledge, the present study was designed with four parts:Part 1: The impact of admission blood glucose on the prognosis ofpatients with ST-segment elevation myocardial infarction.Part 2: The analysis of different classification methods according to admission glucose levels on the prognosis of patients with ST-segmentelevation myocardial infarction.Part 3: The impact of mean blood glucose level on the prognosis ofpatients with ST-segment elevation myocardial infarction.Part 4: The comparison of glucose levels with history of diabetes inthe risk assessment of the prognosis in patients with ST-segmentelevation myocardial infarction.Part 1: The impact of admission blood glucose on theprognosis of patients with ST-segment elevationmyocardial infarctionObjective: To evaluate the association of the admission blood glucoselevel and the short term mortality and combined end point events inpatients with ST-segment elevation acute myocardial infarction (STEMI)with or without history of DM.Methods: This is an observational analysis of 7446 Chinese STEMIpatients from a global randomized controlled trial which included patientspresented within 12 hours of symptom onset. Plasma glucose was measuredprospectively at hospital admission, 6 and 24 hours after hospitalization,respectively. The patients were grouped by the admission blood glucoselevel of:＜4.5mmol/l (defined as the hypoglycemia group), 4.5～5.5mmol/L (as control group), 5.6～7.0 mmol/L (as borderline group),7.1～8.5 mmol/L(as mild hyperglycemia group), 8.6～11.0mmol/L (asmoderate hyperglycemia group),＞11.0 mmol/L(as severe hyperglycemiagroup). The incidence of all-cause mortality and combined end pointevents of death, re-infarction, cardiogenic shock, recurrence ischemia, andstroke within 7 days and 30 days were analyzed in patients of variousadmission glucose groups.Results: Compared with the glucose of 4.5～5.5mmol/L group, seven-daymortality and combined end point events increased as plasma glucoseincreased. There was significant difference in mortality and combined endpoint events in patients with various admission glucose groups (P＜0.001).The lowest mortality and combined end point events occurred in the control group (5.2%, 11.7%, respectively). The highest mortality and combinedend point events occurred in the severe hyperglycemia group (15.3%,24.1%, respectively). 30-day mortality and combined end point eventsincreased as plasma glucose increased also. There were significantdifferences in mortality and combined end point events in patients withdifferent admission glucose groups (P＜0.001). Compared with the glucoseof 4.5～5.5mmol/L group, 30-day mortality and combined end point eventsincreased in patients with hypoglycemia(10.2% vs. 6.3%, P=0.020, 14.2%vs. 9.3%, p=0.013, respectively), The lowest mortality and combined endpoint events occurred in the control group (6.3%, 9.3%, respectively). Thehighest mortality and combined end point events occurred in the severehyperglycemia group (18.6%, 24.8%, respectively).Multivariate logistic regression analysis showed that, as compared withglucose of 4.5～5.5mmol/L, the moderate and the severe hyperglycemiagroups had an increased mortality within 7-day of 56% (OR=1.56, 95%CI1.07-2.26, P=0.002) and 164% (OR=2.64, 95%CI 1.82-3.83, P＜0.001)respectively; the moderate and the severe hyperglycemia groups had aincreased combined end point events within 7-day of 34% (OR=1.34,95%CI 1.03-1.74,P=0.027) and 84% (OR=1.84, 95%CI 1.41-2.41, P＜0.001)respectively; the mild, moderate and the severe hyperglycemia groups hada mortality within 30-day increasing of 46% (OR=1.46, 95%CI1.03-2.07,P=0.010) , 58% (OR=1.58, 95%CI 1.13-2.22,P=0.002) and126% (OR=2.26, 95%CI 1.62-3.14, P＜0.001) respectively; the mild,moderate and the severe hyperglycemia groups had a combined end pointevents within 30-day increasing of 42% (OR=1.42, 95%CI 1.06-1.91,P=0.018) , 53% (OR=1.53, 95%CI 1.14-2.06, P=0.005)and 130%(OR=2.30, 95%CI 1.71-3.09, P＜0.001) respectively.Conclusion: Moderate and severe hyperglycemia were associated withincreased 7-day mortality and combined end point events. Mild, moderateand severe hyperglycemias were associated with 30-day mortality andcombined end point events. Admission blood glucose level is an importantindependent risk factor of short-term prognosis. Part 2: The analysis of different classification methodsaccording to admission glucose levels on the prognosis ofpatients with ST-segment elevation myocardial infarction.Objective: To compare the different classification methods by admissionblood glucose levels on the short term mortality and major combined endpoint events in patients with ST-segment elevation acute myocardialinfarction (STEMI).Methods: Based on the same patients database of part 1, the relationbetween quartile groups and short term mortality and combined end pointevents of death, re-infarction, cardiogenic shock, recurrence ischemia, andstroke within 7-day and 30-day was analyzed. Comparing nested modelsfor mortality and combined end point events within 7-day and 30-day wereconstructed to evaluate the prognostic value of two classification methodsof quartile and six groups (in Part 1) for admission blood glucose levels.Results: Patients were stratified into quartiles groups (Q1 to Q4) byadmission blood glucose concentrations of Q1 (≤5.9mmol / L), Q2(6.0-7.3mmol / L), Q3 (7.4-9.7mmol / L) and Q4 (≥9.8mmol / L). Themortality and combined end point events within 7-day increasedincrementally across the quartile groups, from 4.9% in Q2 to 14.0% in Q4(p＜0.001), 11.6% in Q1 to 22.6% in Q4(p＜0.001), respectively. Themortality and combined end point events within 30-day increasedincrementally across the quartile groups, from 7.7% in Ql to 17.1% in Q4(p＜0.001), 10.6% in Q1 to 22.2% in Q4(p＜0.001), respectively.Multivariate logistic regression analysis showed that, as compared with Q1,the Q3 and the Q4 had an increased mortality within 7-day of 50%(OR=1.50, 95%CI 1.14-1.96,P=0.003) and 131% (OR=2.31, 95%CI1.78-3.01,P＜0.001) respectively; the Q3 and the Q4 had an increasedcombined end point events within 7-day of 45% (OR=1.45, 95%CI1.19-1.76,P＜0.001) and 78% (OR=1.78, 95%CI 1.46-2.17,P＜0.001)respectively; the Q3 and the Q4 had an increased mortality within 30-dayof 39% (OR=1.39, 95%CI 1.09-1.77,P=0.008) and 107% (OR=2.07,95%CI 1.63-2.63,P＜0.001) respectively; the Q3 and the Q4 had an increased combined end point events within 30-day of 39% (OR=1.39,95%CI 1.12-1.72,P=0.003) and 75% (OR=1.75, 95%CI 1.42-2.17,P＜0.001)respectively. Nested models were compared to determine whether logisticregression models that included the method of six groups provided asignificantly better fit than did logistic regression models includedquartile groups. It showed that both classification methods can be used toanalyze the relation of AG and adverse outcomes. The admission bloodglucose classified by six groups is superior in perdiction of prognosis forcombined end point events compared to quartile grouping.Conclusion: Mild admission hyperglycemia (≥7.4mmol/L) wasindependent predictors of 7-day and 30-day mortality and combined endpoint events. Admission hyperglycemia was an independent predictor ofshort term mortality and combined end point events regardless ofclassification methods defined by admission blood glucose.Part 3: The impact of mean blood glucose level on theprognosis of patients with ST-segment elevation myocardialinfarction.Objective: To evaluate the association of the first 24 hour mean bloodglucose (MBG) level during hospitalization and the short term mortalityand combined end point events in patients with ST-segment elevationacute myocardial infarction (STEMI). To compare the prognostic valueof AG and MBG in patients with STEMI.Methods: This is an observational analysis of 7446 Chinese STEMIpatients from a global randomized controlled trial which included patientspresented within 12 hours of symptom onset. Plasma glucose was measuredat hospital admission and 6 and 24 hours after admission, respectively. Themean blood glucose level through the first 24 hours for each patient wascalculated. Patients were stratified into six groups according to their MBGlevels of＜4.50mmol/l (defined as the hypoglycemia group), 4.5～ 5.5mmol/l (control group), 5.6～7.0 mmol/L (borderline group), 7.1～8.5mmolL (mild hyperglycemia group), 8.6～11.0 mmol/L (moderatehyperglycemia group) and＞11.0 mmol/L (severe hyperglycemia group).The incidence of all-cause mortality and combined end point of death,re-infarction, cardiogenic shock, recurrence ischemia, and stroke within 7days and 30 days in patients with various hyperglycemia levels wereanalyzed. Nested models were compared to determine whether logisticregression models that included MBG provided a significantly better fitthan did logistic regression models included AG.Results: Compared with the MBG of 4.5～5.5mmol/L group, 7-daymortality and combined end point events increased as plasma MBG levelsincreased. There were significant differences in mortality and combinedend point events in patients with various MBG groups (P＜0.001). Thelowest 7-day mortality occurred in the control group (4.7%). The lowest7-day combined end point events occurred in the hypoglycemia group(14.3%). The highest 7-day mortality and combined end point eventsoccurred in the severe hyperglycemia group (16.9%, 25.6%, respectively).30-day mortality and combined end point events increased as MBG levelsincreased. There were significant differences in mortality and combinedend point events in patients with various MBG groups (P＜0.001).Compared with the control group, 30-day combined end point eventsincreased in patients with hypoglycemia (P=0.013). The lowest 30-daymortality and combined end point events occurred in the control group(6.8%, 9.7%, respectively). The highest 30-day mortality and combined endpoint events occurred in the severe hyperglycemia group (20.6%, 25.7%,respectively).Multivariate logistic regression analysis showed that, as compared withMBG of 4.5～5.5mmol/L, the mild, moderate and the severehyperglycemia groups had an increased mortality within 7-day of 56%(OR=1.56, 95%CI 1.07-2.29,P=0.022), 61% (OR=1.61, 95%CI 1.09-2.38,P=0.018) and 230% (OR=3.30, 95%CI 2.24-4.84,P＜0.001), respectively;the mild, moderate and the severe hyperglycemia groups had an increasedcombined end point events within 7-day of 56% (OR=1.56, 95%CI1.09-2.05,P=0.001), 66% (OR=1.66, 95%CI 1.26-2.20,P＜0.001), and154% (OR=2.54, 95%CI 1.92-3.36, P＜0.001), respectively; the mild, moderate and the severe hyperglycemia groups had an increased mortalitywithin 30 days increasing of 41% (OR=1.41, 95%CI 1.00-1.97, P=0.048),43% (OR=1.43, 95%CI 1.03-1.98, P=0.032) and 185% (OR=2.85, 95%CI2.04-3.97, P＜0.001), respectively; the moderate and the severehyperglycemia groups had an increased combined end point events within30-day of 59% (OR=1.59, 95%CI 1.19-2.12, P=0.002) , 148% (OR=2.48,95%CI 1.85-3.33, P＜0.001), respectively. The prognostic value of the AGand MBG using nested models showed that MBG is a superior predictor ofprognosis than AG (P＜0.001).Conclusion: Elevated MBG (≥7.1mmol/L) level is an independentpredictor of 7-day and 30-day mortality and combined end point events.MBG is superior to AG in the assessment of short-term risk.Part 4: The comparison of glucose levels with history ofdiabet in the risk assessment of the prognosis in patients withST-segment elevation myocardial infarctionObjective: To compare the predictive value of the admission blood glucoselevel and history of diabetes in patients with ST-segment elevation acutemyocardial infarction (STEMI).Methods: This is an observational analysis of 7446 Chinese STEMIpatients from a global randomized controlled trial which included patientspresented within 12 hours of symptom onset. Patients were divided by thepresence or absence of known history of diabetes mellitus (DM). Eachgroup was sub-grouped by quartile. The predictive value and the interactionof AG by quartile grouping and history of DM on mortality and combinedend point events were analyzed.Results: In diabetes group, 7-day mortality increased significantly asplasma glucose increased (p＜0.001), but not in combined end point events(P=0.133) . 30-day combined end point events significantly increased asplasma glucose increased (p=0.029), but not in mortality (P=0.065). 7-dayand 30-day mortality and combined end point events increased as plasmaglucose increased with significance in patients without diabetes (p＜0.001). There was no difference on mortality and combined end point eventsbetween diabetic group and nondiabetic group with each AG group.Multivariate logistic regression analysis showed that diabetes history alonepredicted 7-day and 30-day mortality (OR= 1.47, 95%CI=1.14-1.90,p=0.003, OR=1.40,95%CI=1.12-1.75, p=0.0013, respectively). Theprognostic value both on mortality and combined end point events fordiabetes was eliminated after adjusting for admission glucose level.Conclusion: Hyperglycemia on admission is an independent risk factor forthe short-term outcomes in patients with STEMI with and without historyof diabetes. Diabetes mellitus is not a predictor of adverse outcomes afteradjusting for admission glucose.Final conclusions: Admission blood glucose level is an importantindependent predictor of mortality and combined end point events of death,re-infarction, cardiogenic shock, recurrence ischemia, and stroke within7-day and 30-day in patients with and without known diabetes regardless ofthe mechanism of admission hyperglycemia and classification methodsdefined by admission blood glucose. Mild hyperglycemia(AG≥7.1mmol/L ) had already increased significantly the 30-day mortality. 24hhMBG is superior to AG in the assessment risk, but AG should be remainedpredictor for prognosis. The prognostic value both on mortality andcombined end point events for diabetes was eliminated after adjusting foradmission glucose level.
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