BACKGROUND - Red blood cell distribution width (RDW) is a measure of size variability in the red blood cell population (anisocytosis). Increased RDW may arise from any condition that affects erythropoiesis or the survival of erythrocytes. RDW has been associated with poor prognosis in patients with type 2 diabetes (T2D). Whether RDW is a risk marker for adverse cardiovascular outcomes or also a marker of non‐cardiovascular health concerns is of clinical importance.

AIMS - To determine the clinical correlates of increased RDW, its potential mechanistic association with multiple circulating biomarkers, and its prognostic value, in patients with (T2D) who had a recent acute coronary syndrome.

METHODS - We used time‐updated Cox models applied to patients enrolled in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) 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 longer duration of diabetes duration, and increased comorbidities. An RDW >16.1% (both baseline and time‐updated) was independently associated with the study primary composite outcome of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death (time‐updated adjusted HR =1.36, 95%CI =1.16–1.61, p < 0.001), all‐cause death (time‐updated adjusted HR =2.01, 95%CI =1.60–2.53, p < 0.001), as well as mortality from non‐CV causes (time‐updated adjusted HR =2.67, 95%CI =1.72–4.15, p < 0.001). RDW had a weak‐to‐moderate correlation with hemoglobin 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.

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