title: Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort Study From the Women's Health Initiative.
abstract: BACKGROUND
  Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors.
  
  
  RESULTS
  We identified 15,288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification.
  
  
  CONCLUSIONS
  Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus.
  
  
  BACKGROUND
  URL: http://www.clinicaltrial.gov. Unique identifier: NCT00000611.
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.). mdschmiegelow@gmail.com.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Schmiegelow
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Haley
authors.initials: H
authors.lastname: Hedlin
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: From the The Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (M.D.S., M.A.H.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M.D.S.); The Department of Medicine, Stanford University School of Medicine, Stanford, CA (H.H., M.L.S., M.A.H.); Department of Epidemiology Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (R.H.M.); Department of Family and Preventive Medicine, University of California, San Diego (M.A.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (J.G.R.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hlatky
mesh_terms: D000368:Aged; D015992:Body Mass Index; D002318:Cardiovascular Diseases; D015331:Cohort Studies; D015444:Exercise; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D017698:Postmenopause; D018570:Risk Assessment; D012307:Risk Factors; D016387:Women's Health
keywords: coronary heart disease; insulin resistance; ischemic stroke; women