The association of hemoglobin a1c with incident heart failure among people without diabetes: the atherosclerosis risk in communities study

Abstract

Objective: This study sought to investigate an association of HbA1c (A1C) with incident heart failure among individuals without diabetes and compare it to fasting glucose.

Research design and methods: We studied 11,057 participants of the Atherosclerosis Risk in Communities (ARIC) Study without heart failure or diabetes at baseline and estimated hazard ratios of incident heart failure by categories of A1C (<5.0, 5.0-5.4 [reference], 5.5-5.9, and 6.0-6.4%) and fasting glucose (<90, 90-99 [reference], 100-109, and 110-125 mg/dl) using Cox proportional hazards models.

Results: A total of 841 cases of incident heart failure hospitalization or deaths (International Classification of Disease, 9th/10th Revision, 428/I50) occurred during a median follow-up of 14.1 years (incidence rate 5.7 per 1,000 person-years). After the adjustment for covariates including fasting glucose, the hazard ratio of incident heart failure was higher in individuals with A1C 6.0-6.4% (1.40 [95% CI, 1.09-1.79]) and 5.5-6.0% (1.16 [0.98-1.37]) as compared with the reference group. Similar results were observed when adjusting for insulin level or limiting to heart failure cases without preceding coronary events or developed diabetes during follow-up. In contrast, elevated fasting glucose was not associated with heart failure after adjustment for covariates and A1C. Similar findings were observed when the top quartile (A1C, 5.7-6.4%, and fasting glucose, 108-125 mg/dl) was compared with the lowest quartile (<5.2% and <95 mg/dl, respectively).

Conclusions: Elevated A1C (> or =5.5-6.0%) was associated with incident heart failure in a middle-aged population without diabetes, suggesting that chronic hyperglycemia prior to the development of diabetes contributes to development of heart failure.

FIG. 1.

Incident rates of heart failure (HF) according to A1C and fasting glucose. The graph shows incidence rates (per 1,000 person-years) and 95% CIs (shaded area) of heart failure with spline terms of A1C (knots at 5.0, 5.5, and 6.0%) (A) and fasting glucose (knots at 5.0, 5.6, and 6.1 mmol/l [90, 100, and 110 mg/dl]) (B) adjusted for age, sex, and race. The histograms represent the frequency distribution of A1C (4.5–6.5%) and fasting glucose (4.2–6.9 mmol/l [75–125 mg/dl]) in the study sample.

FIG. 2.

Hazard ratios (HRs) of heart failure per 1% unit increase in A1C. Hazard ratios overall and within subgroups adjusted for the same covariates as model 2 in Table 2 are shown. Error bars represent 95% CIs. eGFR = estimated glomerular filtration rate.