Association Between Age at Diagnosis of Atrial Fibrillation and Subsequent Risk of Ischemic Stroke

Abstract

Background: Atrial fibrillation (AF) significantly increases the ischemic stroke risk. However, the relationship between age at diagnosis of AF and subsequent stroke risk remains poorly understood.

Methods and results: We analyzed data from 5 prospective cohorts: ARIC (Atherosclerosis Risk in Communities) study, CHS (Cardiovascular Health Study), CARDIA (Coronary Artery Risk Development in Young Adults), MESA (Multi-Ethnic Study of Atherosclerosis), and Framingham Heart Study (including Offspring cohort and the Third-Generation cohorts). Cox regression models and competing risk survival analyses were used to assess incidence rates and hazard ratios (HRs) for ischemic stroke stratified by age groups. Among 47 239 participants (median follow-up: 21.1 years), 6689 (14.2%) developed AF, and 536 (8.0%) subsequently experienced ischemic stroke. Younger age at AF diagnosis was significantly associated with a higher ischemic stroke risk. Fully adjusted HRs for ischemic stroke were 5.35 (95% CI, 3.56-8.03), 2.99 (95% CI, 2.32-3.86), 2.13 (95% CI, 1.75-2.58), and 1.93 (95% CI, 1.59-2.34) for AF diagnosed at ages 55, 65, 75, and 85, respectively. Compared with participants without AF at age 55, HRs for ischemic stroke were 7.30 (95% CI, 3.27-16.31) for AF diagnosed >10 years earlier, 4.98 (95% CI, 2.99-8.29) for 6 to 10 years earlier, and 4.60 (95% CI, 1.48-14.34) for ≤5 years earlier (P-trend <0.001). The presence of AF yielded a 13.9 years earlier occurrence of ischemic stroke among those with AF diagnosis at 55 years compared with 1.5 years earlier at age 85.

Conclusions: Younger age at AF diagnosis was associated with a higher risk of subsequent ischemic stroke.

Keywords: age at diagnosis; atrial fibrillation; ischemic stroke.

Figure 1. Cumulative hazards (nonadjusted Nelson–Aalen) of ischemic stroke in relation to age at diagnosis of atrial fibrillation.

A, At age 55, individuals diagnosed with AF before this age have the highest risk of ischemic stroke (HR, 6.41 [95% CI, 4.28–9.59]); B, at age 65, stroke risk remains elevated (HR, 3.26 [95% CI, 2.53–4.19]); C, at age 75, the risk decreases further (HR, 2.13 [95% CI, 1.76–2.58]); and (D) at age 85, individuals diagnosed with AF still exhibit an elevated cumulative risk (HR, 1.92 [95% CI, 1.58–2.32]). For adjusted HR, please see Table 2. AF indicates atrial fibrillation; and HR, hazard ratio.

Figure 2. Expected age of ischemic stroke in relation to age at diagnosis of atrial fibrillation.

The differences of expected ischemic stroke age between individuals with and without AF at ages 55, 60, 65, 70, 75, 80, and 85 years were 13.9, 11.7, 8.2, 5.3, 4.0, 2.4, and 1.5 years, respectively. AF indicates atrial fibrillation.

Figure 3. The relative risk of ischemic stroke in relation to elapsed time since AF index date in patients with AF compared with age‐matched individuals without AF among different age categories.

AF indicates atrial fibrillation.