Cardiovascular disease is the leading cause of death in patients with
type 2 diabetes, with more than 77,000 deaths each year. The risk remains high despite normalization of well-known cardiovascular risk factors, and the impact of
glycemic control on risk reduction remains controversial. Deleterious changes in fibrinolysis, platelet function, and coagulation secondary to
insulin resistance and/or the metabolic derangements of
type 2 diabetes have emerged as likely mechanisms underlying increased cardiovascular risk.
Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. Thus, elevated concentrations of
PAI-1 promote persistence of clots. Concentrations of
PAI-1 are elevated in the blood and vessel walls of patients with
type 2 diabetes or other
insulin-resistant states. We have hypothesized that increased
PAI-1 can create conditions favorable to the evolution of unstable,
lipid-laden atherosclerotic coronary plaques, thereby rendering patients with diabetes highly susceptible to
rupture of vulnerable plaques and
acute coronary syndromes. Therapeutic interventions that may alter this evolution by reducing concentrations of
PAI-1 or correct metabolic derangements that promote it are being studied. Antiplatelet
therapy has been directed at the increased platelet reactivity characteristic of patients with diabetes. Its use has reduced complications after
percutaneous coronary intervention following the onset of
unstable angina. Amelioration of
diabetic cardiomyopathy by correction of impaired myocardial energy metabolism and limiting the accumulation of
advanced glycation end products is being evaluated as well.