INSULIN AND CORONARY-ARTERY DISEASE - IS SYNDROME-X THE UNIFYING HYPOTHESIS

OBJECTIVE: TO review data supporting the hypothesis that syndrome X pl ays a major role in the pathogenesis of coronary artery disease (CAD), and the effects of lifestyle factors and pharmacologic interventions on insulin, other metabolic parameters, and outcomes. DATA SOURCES: ME DLINE (January 1966-August 1997) and Current Contents database searche s identified applicable English-language experimental trials, epidemio logic studies, reviews, and editorials. STUDY SELECTION AND DATA EXTRA CTION: Studies that were included addressed the role of insulin resist ance and hyperinsulinemia in the pathogenesis of CAD or the effects of lifestyle factors and pharmacologic interventions on metabolic parame ters and outcomes. DATA SYNTHESIS: The main characteristics of syndrom e X are hyperinsulinemia and insulin resistance. These result in secon dary syndrome X features, including hyperglycemia, increased very-low- density lipoprotein concentrations, decreased high-density lipoprotein cholesterol, and hypertension. Insulin resistance is worsened by obes ity, and insulin has been shown to contribute to the development of hy pertension. Other studies demonstrate that smoking adversely affects g lucose and insulin concentrations. Animal studies have linked hyperins ulinemia and atherogenesis. These animal data have been confirmed by s everal large prospective and population studies that have identified a ssociations between hyperinsulinemia and CAD. CONCLUSIONS: Strong evid ence links insulin resistance and hyperinsulinemia to CAD. Lifestyle m odifications play an important role in decreasing cardiovascular risk, and clinicians should strongly encourage such changes. Clinicians mus t also carefully consider the effects of antihypertensive, antihypergl ycemic, and antidyslipidemic agents on patients' metabolic profiles wh en choosing appropriate therapeutic regimens. However, outcome data on many potentially beneficial agents, including calcium antagonists, al pha(1)-adrenergic antagonists, angiotensin-converting enzyme inhibitor s, metformin, acarbose, and troglitazone, are not yet available.