Red cell distribution width in patients with diabetes and myocardial infarction: An analysis from the EXAMINE trial

AIM: To determine the clinical correlates of increased red blood cell distribution width (RDW), its potential mechanistic association with multiple circulating biomarkers, and its prognostic value in patients with type 2 diabetes (T2D) who had a recent acute coronary syndrome. METHODS: We used time-updated Cox models applied to patients enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. RESULTS: A total of 5380 patients were included, the median age was 61 years and 32% were women. Patients with higher RDW were older, more frequently women, with a longer diabetes duration and increased co-morbidities. An RDW of more than 16.1% (both baseline and time-updated) was independently associated with the study primary composite outcome of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death (time-updated adjusted HR = 1.36, 95% CI = 1.16-1.61, p < .001), all-cause death (time-updated adjusted HR = 2.01, 95% CI = 1.60-2.53, p < .001), as well as mortality from non-cardiovascular causes (time-updated adjusted HR = 2.67, 95% CI = 1.72-4.15, p < .001). RDW had a weak-to-moderate correlation with haemoglobin and circulating markers that reflected inflammation, apoptosis, fibrosis and congestion. Alogliptin did not alter RDW values. CONCLUSIONS: RDW is a marker of disease severity associated with a multitude of poor outcomes, including both cardiovascular and non-cardiovascular death. RDW correlated modestly with inflammatory, pro-apoptotic, pro-fibrotic and congestion markers, and its levels were not affected by alogliptin during the course of the trial.