Association of long-term change and variability in glycemia with risk of incident heart failure among patients with type 2 diabetes: A secondary analysis of the ACCORD trial

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 HbA_1c was assessed from stabilization of HbA_1c 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 HbA_1c 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 hos-pitalization. Substantial changes in HbA_1c 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 HbA_1c). Greater long-term variability in HbA_1c 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 HbA_1c were independently associated with risk of HF among patients with T2DM.