A Test in Context: Hemoglobin A_1c and Cardiovascular Disease

Measurement of glycated hemoglobin (HbA_1c), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of HbA_1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA_1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA_1c reduction and cardiovascular disease prevention in patients with diabetes is more complex, with data from large randomized trials published over the past decade providing clear evidence that lowering of HbA_1c per se is an inadequate marker for a therapeutic regimen's impact on cardiovascular outcomes and patient survival. Recent revisions in professional society guidelines moved away from uniform recommendations and toward a more nuanced, patient-centered approach to HbA_1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA_1c contemporary assays and their limitations.