Myocardial infarction and hyperglycemia

We read with interest the report of Cao and coworkers1 J.J. Cao, M. Hudson, M. Jankowski, F. Whitehouse and W.D. Weaver, Relation of chronic and acute glycemic control on mortality in acute myocardial infarction with diabetes mellitus, Am J Cardiol 96 (2005), pp. 183–186. Article | PDF (62 K) | View Record in Scopus | Cited By in Scopus (45)1 describing the existence of a relation between elevated admission glucose levels and adverse outcome and mortality in diabetic patients during myocardial infarction (MI). Although it has been described in other patient populations, the question of whether hyperglycemia is a mediator or marker of adverse outcomes remains unclear. Recommendations are being developed for strict glucose management in all hospitalized patients; however, glucose measurement has not been included in MI risk indexes, and current MI guidelines do not suggest specific therapeutic targets for glucose control. This relative lack of guidance concerning the risk management of patients with MI and hyperglycemia may be because many aspects of the relation between glucose levels and mortality in patients with MI have not been adequately defined, nor have the pathogenetic mechanisms responsible for adverse outcomes. This gap in knowledge may limit treatment of elevated glucose levels in hospitalized patients with acute MI and hyperglycemia. However, an active inflammatory infiltrate in the peri-infarct area and in unaffected viable myocardium has been described in patients with recent MI.2 The inflammatory burden in the peri-infarct region is associated with worse short- and mid-term outcomes. This is not surprising because the inflammatory response in this region probably amplified myocardial necrosis. In this context, we have shown that hyperglycemic stress during MI is associated with increased levels of some inflammatory markers, including C-reactive protein and interleukin-18, and enhanced expression of natural killer cells (CD16/CD56) associated with reduced expression of some T cells (CD152) known to limit the immune process in patients presenting with acute MI.3 These results fit with animal studies showing increased levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-18) and peroxynitrite (an index of oxidative stress) in the heart tissue of hyperglycemic mice. These correlated strictly with the glucose levels,4 leading to myocardial apoptosis and greater infarct size. Finally, analysis of ventricular biopsy specimens obtained from type 2 diabetic patients presenting with acute coronary syndromes and undergoing coronary bypass surgery have shown reduced expression of some important angiogenic factors, such hypoxia-inducible factor-1α and vascular endothelial growth factor, compared with nondiabetic patients with ischemia.5 The results of these studies suggest that hyperglycemia amplifying oxidative stress and the inflammatory responses to myocardial ischemia, as well as impairing angiogenesis factors, may affect the prognosis of patients presenting with MI.