Background: The CHA2DS2-VASc score has been widely used to predict stroke in patients with atrial fibrillation (AF). Recently, it was reported that the CHA2DS2-VASc score helps predict cardiovascular disease (CVD) or all-cause mortality in patients with or without AF. However, few reports have examined the association between this score and mortality in hemodialysis (HD) patients. Methods: We analyzed 557 consecutive patients who initiated HD at our facilities between February 2005 and October 2017. The CHA2DS2-VASc score was calculated at the time of initiation of HD. Patients were then categorized into three groups according to their CHA2DS2-VASc scores: 0–1 (low), 2–3 (intermediate), and 4–9 (high). Multivariate Cox proportional hazards analysis was used to assess independent risk factors for 3-year all-cause mortality. Results: During the 3-year follow-up period, 153 (27.5%) patients died (cardiovascular death: n = 88). According to multivariate analysis, serum albumin (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43–0.85, p = 0.003), creatinine (HR 0.91, 95% CI 0.84–0.99, p = 0.049), and CHA2DS2-VASc score (HR 1.33, 95% CI 1.20–1.46, p < 0.001) were associated with 3-year all-cause mortality. Compared with patients in the low CHA2DS2-VASc score group, those in the intermediate- and high-score groups had a higher risk for all-cause and CVD mortality (all-cause mortality: HR 1.77, 95% CI 1.23–2.55, p = 0.002 and HR 2.94, 95% CI 1.90–4.53, p < 0.001, respectively; CVD mortality: HR 1.82, 95% CI 1.27–2.59, p = 0.001 and HR 2.85, 95% CI 1.88–4.31, p < 0.001, respectively). Conclusion: The CHA2DS2-VASc score is a valuable predictor of 3-year all-cause and CVD mortality in incident HD patients.

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