Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study

Eur J Heart Fail. 2016 Jan;18(1):94-102. doi: 10.1002/ejhf.455. Epub 2015 Dec 13.


Aims: Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c ). Using the time-weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF.

Methods and results: A time-weighted mean HbA1c was calculated using all HbA1c measurements following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1-7.0%, 7.1-8.0%, 8.1-9.0%, and >9.0%). The relationship between time-weighted mean HbA1c and all-cause death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the study criteria. During a median follow-up of 2.8 years, there were 826 (57.1%) deaths, with a crude death rate of 155 deaths per 1000 person-years [95% confidence interval (CI) 144-166]. A Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1-8.0%) as the reference, showed a U-shaped relationship between HbA1c and outcome [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8-3.4; HbA1c 6.1-7.0%, HR 1.4, 95% 1.1-1.7; HbA1c 8.1-9.0%, HR 1.3, 95% CI 1.0-1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4-2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 0.61-0.93) but not other drug classes.

Conclusions: In patients with T2DM and CHF, our study shows a U-shaped relationship between HbA1c and mortality, with the lowest risk in patients with modest glycaemic control (HbA1c 7.1-8.0%) and those treated with insulin sensitizers.

Keywords: Diabetes; HbA1c; Heart failure; Metformin; Outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Female
  • Glycated Hemoglobin A / analysis*
  • Heart Failure* / blood
  • Heart Failure* / complications
  • Heart Failure* / diagnosis
  • Heart Failure* / mortality
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Monitoring, Physiologic / methods*
  • Mortality
  • Outcome Assessment, Health Care
  • Proportional Hazards Models
  • Risk Assessment / methods
  • United Kingdom / epidemiology


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Metformin