title: Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis.
abstract: OBJECTIVE
  People with diabetes have an increased risk of coronary artery disease (CAD). An unanswered question is what portion of CAD can be attributed to insulin resistance, related metabolic variables, and other known CAD risk factors.
  
  
  METHODS
  The Archimedes model was used to estimate the proportion of myocardial infarctions that would be prevented by maintaining insulin resistance and other risk factors at healthy levels. Person-specific data from the National Health and Nutrition Examination Survey 1998-2004 were used to create a simulated population representative of young adults in the U.S. This population was then entered into a series of simulated clinical trials designed to explore the effects of each risk factor. Each trial had a control arm (all risk factors were allowed to progress without interventions) and a treatment arm (a risk factor was held to its value in young healthy adults). The trials continued for 60 years. The effects of these hypothetical "cures" of each risk factor provide estimates of their impact on CAD.
  
  
  RESULTS
  In young adults, preventing insulin resistance would prevent approximately 42% of myocardial infarctions. The next most important determinant of CAD is systolic hypertension, prevention of which would reduce myocardial infarctions by approximately 36%. Following systolic blood pressure, the most important determinants are HDL cholesterol (31%), BMI (21%), LDL cholesterol (16%), triglycerides (10%), fasting plasma glucose and smoking (both approximately 9%), and family history (4%).
  
  
  CONCLUSIONS
  Insulin resistance is likely the most important single cause of CAD. A better understanding of its pathogenesis and how it might be prevented or cured could have a profound effect on CAD.
authors.affiliation: Archimedes Inc., San Francisco, California, USA. author@archimedesmodel.com
authors.forename: David
authors.initials: D
authors.lastname: Eddy
authors.forename: Len
authors.initials: L
authors.lastname: Schlessinger
authors.forename: Richard
authors.initials: R
authors.lastname: Kahn
authors.forename: Barbara
authors.initials: B
authors.lastname: Peskin
authors.forename: Rick
authors.initials: R
authors.lastname: Schiebinger
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control*; D009749:Nutrition Surveys; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult