Abstract and Introduction
Background Patients with diabetes have increased in-hospital mortality following acute myocardial infarction (AMI), with studies suggesting higher risk with both hypoglycemia and hyperglycemia. We assessed whether a J-shaped relation exists between hemoglobin A1c (A1C) in patients with diabetes and AMI.
Methods We assessed the associations between A1C and in-hospital mortality using data from a nationwide sample of AMI patients who had both prior diabetes and measurement of A1C (N = 15,337).
Results When evaluated continuously, we observed no evidence of a J-shaped relation between A1C and in-hospital mortality in multivariable analysis (test for linearity P = .89). Patients with lowest (<5.5%) and highest A1C (≥9.5%) had a crude mortality rate of 4.6% and 2.8%, respectively, compared with 3.8% among those in the referent A1C category (6.5% to <7%). In multivariable regression, we observed no association between low A1C (<5.5%, odds ratio 0.81, 95% CI 0.47–1.39) or high A1C (A1C ≥9.5, odds ratio 1.31, 95% CI 0.94–1.83) and mortality as compared with the referent group. These findings can only be generalized to the subset of patients with diabetes who had A1C assessed during their hospitalization; these patients tended to be healthier than those in whom A1C was not assessed.
Conclusion In this large contemporary cohort of patients with diabetes presenting with AMI, we did not observe a J-shaped association between A1C and mortality.
Observational studies have consistently demonstrated an association between higher levels of hemoglobin A1c (A1C) and adverse cardiovascular disease outcomes and mortality among patients with diabetes in the outpatient setting. A recent study has shown an association between low values of A1C and all-cause mortality among outpatients with diabetes treated with either oral agents or insulin therapy.
In the acute myocardial infarction (AMI) setting, multiple studies have examined the association between glucose levels and mortality; and a J-shaped relationship has been demonstrated between glucose and mortality among patients both with and without diabetes. However, it has been postulated that the association between both hyperglycemia and hypoglycemia and mortality may be explained by glucose levels serving as a marker of illness severity. This hypothesis is also supported by a recent post-hoc analysis of the Action in Diabetes and Vascular Disease (ADVANCE) trial. Episodes of severe hypoglycemia were associated with both an increased risk of cardiovascular outcomes and mortality, but also a range of non-cardiovascular outcomes. Thus, glucose may be less useful in providing insight into the actual association of glycemic control and outcomes in AMI.
Hemoglobin A1c reflects longer-term glycemic control and is less influenced by acute stress. Therefore, A1C levels may provide insight into the relation between chronic glucose control and patient outcomes. However, available studies that have assessed the relationship between A1C and mortality in the AMI setting have not explicitly examined the association between low A1C levels and mortality. The Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry–Get With The Guidelines provides a large sample of patients with diabetes presenting with MI. The present analyses were designed to assess whether a J-shaped relationship exists between categories of A1C and hospital mortality among patients with diabetes and MI. We hypothesized that low, in addition to high, A1C levels would be associated with higher in-hospital mortality in the AMI setting.