Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: The ARIC Study

Background. Chronic kidney disease (CKD) has been linked to higher stroke risk. Anemia is a common consequence of CKD, and recent evidence suggests anemia may increase risk of cardiovascular events. The combined effect of CKD and anemia on stroke risk, however, has not been investigated thoroughly. We analyzed data from a middle-aged, community-based cohort to determine if CKD and anemia interacted to affect stroke risk. Methods. Data on 13,716 participants in the prospective Atherosclerosis Risk in Communities (ARIC) Study were analyzed to assess the joint effect of CKD and anemia on risk of incident stroke during a 9-year follow-up period. CKD was defined as a creatinine clearance of <60 mL/min. Anemia was defined as hemoglobin levels of <13 g/dL for men or <12 g/dL for women. Results. Overall, CKD was associated with an increase in stroke risk after adjustment for other factors [hazard ratio HR) 1.81; 95% CI 1.26 to 2.02]. However, this association was modified substantially by anemia. In the presence of anemia, CKD was associated with a substantially higher risk of stroke compared to no CKD (HR 5.43; 95% CI 2.04 to 14.41). In contrast, when anemia was not present, CKD was associated with only a modest, nonsignificant elevation in stroke risk (HR 1.41; 95% CI 0.93 to 2.14). The interaction between CKD and anemia on risk of stroke was statistically significant (P < 0.01). Conclusion. Among middle-aged, community-based persons, the combination of CKD and anemia was associated with a substantial increase in stroke risk, independent of other known risk factors for stroke.