The prevalence of admission hyperglycemia (glucose levels of >140
mg/dL) in different epidemiological studies ranges from 51% to >58% of patients admitted with AMI [6
]. In patients with AMI, hyperglycemia at the time of admission regardless of diabetic status has been tied to both long- and short-term negative outcomes [7
]. A number of contemporary investigators, however, have challenged this notion and demonstrated that hyperglycemia after hospital admission may yield a more important prognostic role than admission hyperglycemia in terms of morbidity and mortality [9
]. Suleiman and colleagues, for instance, were able to demonstrate that fasting glucose was superior to admission glucose in predicting 30-day mortality in 735 nondiabetic AMI patients [11
]. Loomba and Arora performed an extensive systemic review and were able to demonstrate that persistent glucose levels offer a better model to predict ACS mortality than on-admission glucose levels [12
]. It has been demonstrated that the use of insulin to lower glucose concentrations decreased negative outcomes in patients with hyperglycemia and myocardial infarction (see Section 3
); however, a mechanism by which hyperglycemia may be a causal factor in poor outcomes in AMI remains a topic of debate. It has been proposed that in AMI patients, decreased levels of blood insulin associated with hyperglycemia may lead to a decrease of glycolytic substrate for cardiac muscle. As a result, the heart has to depend on alternate substrates such as free fatty acids for its metabolism. The accumulation of excessive free fatty acids results in the reduction of myocardial contractility and increases the risk of pump failure and arrhythmias ().
This challenges the assumption that hyperglycemia is simply a “marker” of the stress response mediated by cortisol and noradrenaline [13
]. A meta-analysis by Capes and colleagues in 2000 supported this hypothesis by demonstrating that among nondiabetic patients, those with glucose concentrations between 110 and 143
mg/dL had a 3.9-fold higher risk of death and that those with glucose values between 144 and 180
mg/dL had a 3-fold higher risk of heart failure or cardiogenic shock. Similarly, diabetics with glucose concentrations between 180 and 196
mg/dL had an increased risk of death (relative risk 1.7) [7
Hyperglycemia and its effect on cardiac function.
In addition to decreased contractility, pump failure, and arrhythmia, hyperglycemia in AMI may affect coronary perfusion prior to and following percutaneous coronary intervention (PCI). A 2005 observational analysis by Timmer and colleagues sought to determine how hyperglycemia affected coronary perfusion prior to revascularization in ST-segment elevation myocardial infarction (STEMI) [14
]. In 460 consecutive patients with STEMI who were treated with PCI, 70% had serum glucose levels
mmol/L) on admission, but only 14 percent had a history of diabetes. They were able to demonstrate that the patients with hyperglycemia were significantly less likely to have TIMI grade
(normal) flow prior to PCI compared to those with normoglycemia (). This finding complements those by Lazerri and colleagues in 2010, who were able to demonstrate that glucose serum levels measured after mechanical revascularization were independent predictors of in-hospital mortality in STEMI patients without previously-known diabetes [15
]. Indeed, acute hyperglycemia has been associated with increased platelet activation in diabetic and nondiabetic patients [16
]; coupled with evidence that acute hyperglycemia increases inflammatory responses during STEMI [17
], these findings could explain an impairment in coronary flow that reflects a prothrombotic state and/or endothelial dysfunction associated with hyperglycemia, leading to a greater stress response.
Initial TIMI flow grade according to admission glucose. Worse initial Thrombolysis in Myocardial Infarction (TIMI) flow grade is demonstrated in those with hyperglycemia.
Another interesting aspect of the prognostic value of hyperglycemia in AMI is the differences observed in nondiabetic and diabetic patients. In their 2011 study, Lazerri and colleagues observed that in a cohort of STEMI patients undergoing mechanical revascularization, in-hospital peak glycemia was an independent predictor for early death in patients without previously known diabetes, but not in diabetic STEMI patients. At followup, in hospital peak glycemia was able to affect long-term survival in both diabetic and nondiabetic patients. This data underscores the clinical importance of the prognostic role of in-hospital glucose values and strongly suggests that different glucose targets and thresholds may be pursued in diabetic and nondiabetic STEMI patients [19