CHA₂DS₂VASc score and adverse outcomes in middle-aged individuals without atrial fibrillation

Aims: The CHA₂DS₂VASc score is used to evaluate the risk of thromboembolic events in patients with non-valvular atrial fibrillation. We assessed the prognostic yield of CHA₂DS₂VASc for new-onset atrial fibrillation, cardiovascular morbidity and mortality in a non-atrial fibrillation population. Methods: We analysed a population-based cohort of 22,179 middle-aged individuals with (n = 3542) and without (n = 18,367) a history of atrial fibrillation; we grouped the population into five CHA₂DS₂VASc strata (0–1–2–3–≥4), and compared the risk of major adverse cerebro-cardiovascular events and mortality. Furthermore, we analysed the annual incidence of atrial fibrillation across different CHA₂DS₂VASc strata. Results: Over a median follow-up of 15 years, 1572 patients (6.9%) had ischaemic strokes, 2162 (9.5%) coronary events and 5899 (26%) died. The cumulative incidence of ischaemic stroke in CHA₂DS₂VASc ≥ 4 subjects without atrial fibrillation was similar to patients with atrial fibrillation and CHA₂DS₂VASc 2, with a 10-year crude incidence rate of 0.91 (95% confidence interval (CI) 0.68–1.19) and 1.13 (95% CI 0.93–1.36) ischaemic strokes per 100 patient-years, respectively. CHA₂DS₂VASc in a non-atrial fibrillation population showed higher predictive accuracy for ischaemic stroke compared with an atrial fibrillation population (area under the curve 0.60 vs. 0.56; P = 0.001). In multivariable Cox regression analysis, CHA₂DS₂VASc ≥ 2 was an independent predictor of all-cause death (adjusted hazard ratio (aHR) 2.58; 95% CI 2.42–2.76), cardiovascular death (aHR 3.40; 95% CI 2.98–3.89), ischaemic stroke (aHR 2.20; 95% CI 1.92–2.53) and coronary events (aHR 1.83; 95% CI 1.63–2.04). The cumulative incidence of atrial fibrillation was greater with increasing CHA₂DS₂VASc strata, with an absolute annual incidence of more than 2% per year if CHA₂DS₂VASc ≥ 4. Conclusion: The CHA₂DS₂VASc score is a sensitive tool for predicting new-onset atrial fibrillation and adverse outcomes in subjects both with and without atrial fibrillation.