title: Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in caucasian subjects from the general population: the Bruneck study.
abstract: OBJECTIVE
  The purpose of this study was to evaluate whether insulin resistance is associated to cardiovascular disease (CVD) and to understand whether this association can be explained by traditional and novel CVD risk factors associated with this metabolic disorder.
  
  
  METHODS
  We examined a sample representative of the population of Bruneck, Italy (n = 919; aged 40-79 years). Insulin-resistant subjects were those with a score in the top quartile of the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR). Risk factors correlated with insulin resistance included BMI, A1C, HDL cholesterol, triglycerides, blood pressure, high-sensitivity C-reactive protein (hsCRP), fibrinogen, oxidized LDL, vascular cell adhesion molecule-1 (VCAM-1), and adiponectin. Subjects without CVD at baseline were followed up for 15 years for incident CVD, a composite end point including fatal and nonfatal myocardial infarction and stroke, transient ischemic attack, and any revascularization procedure.
  
  
  RESULTS
  During follow-up, 118 subjects experienced a first symptomatic CVD event. Levels of HOMA-IR were higher at baseline among subjects who developed CVD (2.8) compared with those remaining free of CVD (2.5) (P < 0.05). Levels of HOMA-IR also were significantly correlated (P < 0.05) with most CVD risk factors we evaluated. In Cox proportional hazard models, insulin-resistant subjects had an age-, sex-, and smoking-adjusted 2.1-fold increased risk (95% CI 1.3-3.1) of incident symptomatic CVD relative to non-insulin-resistant subjects. After sequential adjustment for physical activity and classic risk factors (A1C, LDL cholesterol, and hypertension) as well as BMI, HDL cholesterol, triglycerides, and novel risk factors, including fibrinogen, oxidized LDL, hsCRP, VCAM-1, and adiponectin, the association between HOMA-IR and incident CVD remained significant and virtually unchanged (hazard ratio 2.2 [95% CI 1.4-3.6], P < 0.001).
  
  
  CONCLUSIONS
  HOMA-estimated insulin resistance is associated with subsequent symptomatic CVD in the general population independently of all classic and several nontraditional risk factors. These data suggest that insulin resistance may be an important target to reduce CVD risk.
authors.affiliation: Endocrinologia e Malattie del Metabolismo, Ospedale Maggiore, Piazzale Stefani 1, 37126 Verona, Italy. enzobonora@virgilio.it
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Friedrich
authors.initials: F
authors.lastname: Oberhollenzer
authors.forename: Georg
authors.initials: G
authors.lastname: Egger
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Riccardo C
authors.initials: RC
authors.lastname: Bonadonna
authors.forename: Michele
authors.initials: M
authors.lastname: Muggeo
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012307:Risk Factors; D044465:White People / Q000706:statistics & numerical data*
chemical_list: D006442:Glycated Hemoglobin