Elevated red cell distribution width (RDW) and adverse outcomes in patients with atrial fibrillation: new insights from a contemporary prospective study

Abstract Background Red blood cell distribution width (RDW) is a marker of anisocytosis available in standard complete blood counts. Elevated RDW values reflect abnormalities in erythropoiesis but are also associated with aging, systemic inflammation, and chronic diseases. Increasing evidence suggests a prognostic role for higher RDW levels in cardiovascular diseases. Purpose This study aimed to investigate the association between RDW levels and clinical outcomes in patients with atrial fibrillation (AF). Methods We used data from a prospective observational study of patients with AF. Patients were stratified into tertiles based on RDW values at baseline: (i) lowest (RDW ≤ 13.5%), (ii) intermediate (RDW 13.6%-14.6%), and (iii) highest tertile (RDW ≥ 14.7%). All-cause death was the primary outcome. The composite outcome of any thromboembolic event (TE), acute coronary syndrome (ACS), or hospitalization for heart failure (HF) (i.e. Major Adverse Cardiovascular Events - MACE) was also evaluated. Results A total of 940 AF patients were included (median age of 75 years). Baseline comparison between the three groups based on RDW values are shown in the Table. The median age, CHA2DS2-VA score, and burden of comorbidities- such as heart failure, coronary artery disease, hypertension, diabetes, CKD, cancer and cognitive impairment - were significantly and progressively higher across the tertiles. Overall, the use of oral anticoagulants (OAC) was substantially high in the cohort (89.7%) with no significant differences among groups. After a median follow-up of 665 days, we observed significant differences in all-cause mortality rates among the RDW tertiles with the highest tertile showing the highest mortality (10.5% in the lowest vs 12.2% in the intermediate vs 26.4% in the highest tertile, p < 0.001). Kaplan-Meier survival curves are shown in the Figure. Additionally, the rates of MACE were significantly and progressively higher among the tertiles, reaching up to 16.7% in the highest tertile (p = 0.04). At the adjusted Cox regression analysis, the highest RDW tertile was independently associated with a higher risk of all-cause mortality compared with the lowest tertile (adjusted HR 2.01, 95% CI 1.30-3.12). ROC analysis yielded an area under the curve (AUC) of 0.657 (95% CI 0.606-0.707) for RDW in predicting all-cause death. Conclusions In a contemporary cohort of patients with AF, elevated RDW values were significantly associated with an increased risk of all-cause mortality. Our findings suggest that this inexpensive and readily available biomarker may help identify patients at higher risk for adverse outcomes, aiming to improve AF clinical management.