Matthew W Segar1, Kershaw V Patel1, Muthiah Vaduganathan2, Melissa C Caughey3, Javed Butler4, Gregg C Fonarow5, Justin L Grodin1, Darren K McGuire1, Ambarish Pandey6. 1. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 2. Brigham and Women's Hospital Heart and Vascular Center, Department of Medicine, Harvard Medical School, Boston, MA. 3. Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC. 4. Department of Medicine, University of Mississippi Medical Center, Jackson, MS. 5. Ahmanson-UCLA Cardiomyopathy Center, Division of Cardiology, Ronald Reagan UCLA Medical Center, Los Angeles, CA. 6. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX ambarish.pandey@utsouthwestern.edu.
Abstract
OBJECTIVE: To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF. RESULTS: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability. CONCLUSIONS: Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.
OBJECTIVE: To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF. RESULTS: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability. CONCLUSIONS: Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.
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