Predictors of incident heart failure hospitalizations among patients with impaired glucose tolerance: insight from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research study

Circ Heart Fail. 2013 Mar;6(2):203-10. doi: 10.1161/CIRCHEARTFAILURE.112.000086. Epub 2013 Feb 6.


Background: Impaired glucose tolerance and metabolic syndrome are associated with increased risk of heart failure (HF). However, predictors associated with the increased risk of incident HF have not been well characterized. We aimed to identify independent predictors of incident HF hospitalization among patients with impaired glucose tolerance.

Methods and results: In Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR), 9306 research participants with impaired glucose tolerance and ≥1 cardiovascular risk factors were randomized to valsartan versus placebo and nateglinide versus placebo in a 2×2 factorial manner, with a median follow-up of 6.5 years. Using a multivariable Cox proportional hazards model, we analyzed the relationships among baseline clinical factors and the outcome of incident HF hospitalization in patients without history of HF. Significant predictors were identified by forward selection. Increasing age, history of coronary heart disease, and atrial fibrillation or flutter were among several known independent predictors of incident HF hospitalization. Increased waist circumference (hazard ratio per 10 cm, 1.37; 95% confidence interval, 1.21-1.55; P<0.001) and increased urinary albumin-creatinine ratio (P<0.001) were identified as novel predictors. The predictive model for incident HF hospitalization showed good discrimination, with an optimism-corrected C-index of 0.79.

Conclusions: Among research participants with impaired glucose tolerance, there are several easily identifiable predictors of incident HF hospitalization, including traditional risk factors and novel indices of central adiposity and increased urinary albumin-creatinine ratio, which enable further risk stratification and help distinguish patients who could benefit from more aggressive risk factor management.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Aged
  • Albuminuria / diagnosis
  • Albuminuria / epidemiology
  • Albuminuria / urine
  • Biomarkers / urine
  • Blood Glucose / drug effects*
  • Creatinine / urine
  • Cyclohexanes / therapeutic use*
  • Double-Blind Method
  • Female
  • Glucose Metabolism Disorders / blood
  • Glucose Metabolism Disorders / diagnosis
  • Glucose Metabolism Disorders / drug therapy*
  • Glucose Metabolism Disorders / epidemiology
  • Heart Failure / epidemiology*
  • Hospitalization*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nateglinide
  • Nonlinear Dynamics
  • Obesity, Abdominal / diagnosis
  • Obesity, Abdominal / epidemiology
  • Obesity, Abdominal / physiopathology
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / therapeutic use
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Tetrazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Valine / analogs & derivatives*
  • Valine / therapeutic use
  • Valsartan
  • Waist Circumference


  • Biomarkers
  • Blood Glucose
  • Cyclohexanes
  • Hypoglycemic Agents
  • Tetrazoles
  • Nateglinide
  • Phenylalanine
  • Valsartan
  • Creatinine
  • Valine