The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Background: A progressive relationship between hemoglobin A(1c) (HbA(1c)) levels and cardiovascular (CV) events has been observed in persons with and without diabetes. To our knowledge, the nature of such a relationship in patients with symptomatic chronic heart failure (HF) has not been studied.

Methods: A total of 2412 participants (907 with prior diabetes) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program with at least 1 HbA(1c) level were followed up for a median of 34 months. The incidence of the primary outcome (CV death or HF hospitalization), CV death, and total mortality was calculated according to eighths of the usual HbA(1c) level ranging from 5.8% or less to greater than 8.6%. Adjusted and unadjusted hazard ratios per 1% rise in HbA(1c) levels were also calculated.

Results: A total of 99.6% of eligible participants were followed up until they developed an outcome or the study finished. The risk of the primary composite outcome, CV death, hospitalization for worsening HF, and total mortality rose progressively with higher levels of usual HbA(1c) (P for trend <.001). After age and sex were adjusted for, hazards of these outcomes per 1% higher HbA(1c) level were 1.25 (95% confidence interval [CI ], 1.20-1.31), 1.24 (95% CI, 1.17-1.31), 1.25 (95% CI, 1.19-1.31), and 1.22 (95% CI, 1.16-1.29), respectively. This relationship was evident in patients with and without diabetes and with reduced or preserved ejection fraction and persisted after adjustment for diabetes, other risk factors, and allocation to candesartan.

Conclusion: In diabetic and nondiabetic patients with symptomatic chronic HF, the HbA(1c) level is an independent progressive risk factor for CV death, hospitalization for HF, and total mortality.