HbA1c and CVD: Important Considerations for the Interpretation and Use of HbA1c Assays
Hemoglobin A covalently bound to glucose (HbA1c) is the most abundant form of glycated hemoglobin, and its levels are increased in the presence of persistent hyperglycemia. HbA1c has lower biological variability than glucose, does not require fasting or timed collections, and provides a better reflection of longer-term glycemic exposure. However, a number of physiological and pathophysiological factors may influence HbA1c levels, including race, conditions that affect erythrocyte age or lifespan, and conditions that affect hemoglobin production. In addition, the values of HbA1c in children and adolescents and in gestational diabetes remain unclear. Contemporary HbA1c assays have largely overcome early challenges, with advances in standardization underpinned by the ongoing NGSP program. Remaining measurement-related challenges include possible assay interference by hemoglobin variants (such as HbS, HbC, HbE, HbD, HbF) or by naturally occurring chemical modifications of hemoglobin (such as carbamyl Hb). When HbA1c values are used for diabetes diagnosis, prognosis, and therapeutic monitoring, it is important to consider that, although therapeutic interventions that reduce HbA1c also decrease the risk of diabetic microvascular complications, HbA1c reduction per se is a poor predictor of a therapeutic regimen’s impact on macrovascular complications and survival. Use of personalized HbA1c targets is emerging as essential for CVD prevention in diabetes. CVD = cardiovascular disease; HbA1c = glycated hemoglobin A1c; NGSP = National Glycohemoglobin Standardization Program.