The Role of Intensive Glycemic Control in the Management of Patients who have Acute Myocardial Infarction

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Stuart W. Zarich, MD, FACC

Division of Cardiovascular Medicine, Department of Medicine, Bridgeport Hospital,

267 Grant Street, Bridgeport, CT 06610, USA Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA

Individuals who have diabetes mellitus (DM) have a twofold to fourfold increased risk of cardiovascular disease and nearly twice the early mortality from acute myocardial infarction (AMI) compared with nondiabetic subjects [1-5]. Furthermore, the mortality difference between diabetics and nondiabetics continues to increase throughout the first year [4]. For more than 70 years it has been recognized that glucosuria is present frequently in nondiabetic patients who have AMI [6]. Acute hyperglycemia is documented in up to half of all patients who have AMI, whereas previously diagnosed DM is present in only 20% to 25% of these patients [7,8].

Elevated plasma glucose and glycated hemoglobin levels at admission are recognized as independent prognosticators of in-hospital and long-term cardiovascular events in diabetics and nondiabetics who have AMI [8-12]. Acute hyperglycemia is associated with an approximate fourfold risk of death with AMI in nondiabetics compared with a nearly twofold increased risk of death in diabetic individuals [10].

It is not clear whether "stress hyperglycemia" predisposes one to a worse prognosis or is simply a marker for more extensive myocardial damage. Acute hyperglycemia in AMI probably is not related simply to stress-mediated release of coun-terregulatory hormones (catecholamines, gluca-gon, and cortisol) because glucose levels that are measured upon hospital admission do not

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correlate necessarily with the extent of myocardial damage as measured by myocardial enzyme release [9,13]. A large, randomized, controlled trial in diabetics who had AMI showed that reduced short- and long-term mortality in low- and high-risk subjects was associated with lowering plasma glucose with insulin [14-16]. This suggests that hyperglycemia is not just a passive by-product of the stress response in the most critically ill patients. Low-risk diabetic individuals and those who had previous insulin use benefited the most from aggressive management of hyperglycemia.

An alternative explanation for the relationship between glucose levels that are measured upon hospital admission and prognosis is the link between insulin resistance, the metabolic syndrome, and cardiovascular (CV) disease. Metabolic syndrome is characterized by insulin resistance and the association with traditional (the "deadly quartet'' of obesity, hypertension, glucose intolerance, atherogenic dyslipidemia) and novel (endothelial dysfunction, proinflamma-tory state, hypercoagulability) risk factors for the development of CV disease and DM [17,18]. The metabolic syndrome is present in approximately 30% of middle-aged men [17] and is associated with a threefold to fourfold increase in CV mortality as compared with controls, even when patients who had known CV disease and DM were excluded from analysis [18]. Patients who have insulin resistance and frank DM also may have a host of associated conditions (Box 1) that may contribute to a poor CV prognosis.

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