Changes over Time in Hemoglobin A1C (HbA1C) Levels Predict Long-Term Survival Following Acute Myocardial Infarction among Patients with Diabetes Mellitus

Abstract

Frequent fluctuations of hemoglobin A1c (HbA_1C) values predict patient outcomes. However, data regarding prognoses depending on the long-term changes in HbA_1C among patients after acute myocardial infarction (AMI) are scarce. We evaluated the prognostic significance of HbA_1C levels and changes among diabetic patients (n = 4066) after non-fatal AMI. All the results of HbA_1C tests up to the 10-year follow-up were obtained. The changes (∆) of HbA_1C were calculated in each patient. The time intervals of ∆HbA_1C values were classified as rapid (<one year) and slow (≥one year) changes. The outcome was all-cause mortality. The highest mortality rates of 53.8% and 35.5% were found in the HbA_1C < 5.5-7% and ∆HbA_1C = -2.5-(-2%) categories. A U-shaped association was observed between HbA_1C and mortality: adjOR = 1.887 and adjOR = 1.302 for HbA_1C < 5.5% and ≥8.0%, respectively, as compared with 5.5-6.5% (p < 0.001). Additionally, ∆HbA_1C was associated with the outcome (U-shaped): adjOR = 2.376 and adjOR = 1.340 for the groups of <-2.5% and ≥2.5% ∆HbA_1C, respectively, as compared to minimal ∆HbA_1C (±0.5%) (p < 0.001). A rapid increase in HbA_1C (but not decrease) was associated with a greater risk of mortality. HbA_1C values and their changes are significant prognostic markers for long-term mortality among AMI-DM patients. ∆HbA_1C and its timing, in addition to absolute HbA_1C values, should be monitored.

Keywords: acute myocardial infarction; diabetes mellitus; hemoglobin A1c; mortality; prognosis.

Figure A1

The mean values of HbA_1C throughout the follow-up (by follow-up year) among patients who died and among survivors.

Figure A2

Mortality rates (%) according to the ∆HbA_1C category in the rapid- and slow-changing groups. Rapid change—time interval of ∆HbA_1C values < one year; slow change—time interval of ∆HbA_1C values ≥ one year.

Figure 1

(a) The rates and the relative risks of mortality by HbA_1C (adjusted odds ratios and 95% CI) categories; (b) The rates and the relative risks of mortality (adjusted odds ratios and 95% confidence intervals) by HbA_1C categories. (a,b) are the results of separate models. Abbreviations: adjOR—adjusted odds ratio (adjusted for repeated measures), CI—confidence interval, HbA_1C—hemoglobin A1C, ∆HbA_1C—the difference between two HbA_1C tests (later–earlier).

Figure 1

(a) The rates and the relative risks of mortality by HbA_1C (adjusted odds ratios and 95% CI) categories; (b) The rates and the relative risks of mortality (adjusted odds ratios and 95% confidence intervals) by HbA_1C categories. (a,b) are the results of separate models. Abbreviations: adjOR—adjusted odds ratio (adjusted for repeated measures), CI—confidence interval, HbA_1C—hemoglobin A1C, ∆HbA_1C—the difference between two HbA_1C tests (later–earlier).

Figure 2

The associations (adjusted odds ratios and 95% confidence intervals): (a) Between HbA_1C and mortality; (b) Between HbA_1C change (∆HbA_1C) and mortality, adjusted for the potential confounders. The results of the combined model included HbA_1C levels and ∆HbA_1C, adjusted for: repeated measures, time from hospital discharge, age, sex, supraventricular arrhythmias, congestive heart failure, chronic ischemic heart disease, history of myocardial infarction, history of percutaneous coronary intervention, history of a coronary artery bypass graft, atrioventricular block, renal failure, diabetes mellitus, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, neurological disorders, malignancy, anemia, gastrointestinal bleeding, alcohol/drug addiction, type of acute myocardial infarction, severe left ventricular dysfunction, left ventricular hypertrophy and three-vessel/left-main coronary arteries disease. Abbreviations: AdjOR—adjusted odds ratio, HbA_1C—hemoglobin A_1C, HbA_1C change (∆HbA_1C)—the difference between two HbA_1C tests (later–earlier).

Figure 2

The associations (adjusted odds ratios and 95% confidence intervals): (a) Between HbA_1C and mortality; (b) Between HbA_1C change (∆HbA_1C) and mortality, adjusted for the potential confounders. The results of the combined model included HbA_1C levels and ∆HbA_1C, adjusted for: repeated measures, time from hospital discharge, age, sex, supraventricular arrhythmias, congestive heart failure, chronic ischemic heart disease, history of myocardial infarction, history of percutaneous coronary intervention, history of a coronary artery bypass graft, atrioventricular block, renal failure, diabetes mellitus, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, neurological disorders, malignancy, anemia, gastrointestinal bleeding, alcohol/drug addiction, type of acute myocardial infarction, severe left ventricular dysfunction, left ventricular hypertrophy and three-vessel/left-main coronary arteries disease. Abbreviations: AdjOR—adjusted odds ratio, HbA_1C—hemoglobin A_1C, HbA_1C change (∆HbA_1C)—the difference between two HbA_1C tests (later–earlier).

Figure 3

The relative risk (adjusted odds ratios) for mortality according to HbA_1C changes in the rapid- and slow-changing groups. Rapid change—time interval of ∆HbA_1C values < one year; slow change—time interval of ∆HbA_1C values ≥ one year. The numbers represent the p-values for disparity (p for interaction) between the rapid- and slow-changing HbA_1C (separately for each ∆HbA_1C category). Adjusted for: repeated measures, HbA1C levels, time from hospital discharge, age, sex, supraventricular arrhythmias, congestive heart failure, chronic ischemic heart disease, history of myocardial infarction, history of percutaneous coronary intervention, history of a coronary artery bypass graft, atrioventricular block, renal failure, diabetes mellitus, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, neurological disorders, malignancy, anemia, gastrointestinal bleeding, alcohol/drug addiction, type of acute myocardial infarction, severe left ventricular dysfunction, left ventricular hypertrophy and three-vessel/left-main coronary arteries disease. Abbreviations: AdjOR—adjusted odds ratio, HbA_1C—hemoglobin A_1C, HbA_1C change (∆HbA_1C)—the difference between two HbA_1C tests (later–earlier).