LAUSR

Sirs, We appreciate Dr Kawada’s interest [1] in our study [2] and careful consideration of the design. Kawada suggests that design considerations may limit the precision of our estimates and causal interpretation. Specifically, Dr Kawada states that the 1:1 matching ratio employed in our study may limit the precision of observed estimates. Whilst we agree that increasing a matching ratio can improve precision, this gain is most clearly apparent when the number of cases is small [3]. In our study which utilized a nested case control design of 460 case control pairs, little gain in precision would have been obtained by increasing the matching ratio. Additional concerns are raised regarding the causal interpretation of these findings. We agree that further work is needed, such as a randomized control trial, to provide evidence to support causality; however, meta-analyses or systematic review would not be sufficient to infer causality given these would simply be secondary data analysis of observational data. To provide the strongest data available we reported previous findings from eight observational studies, given that clinical trial data examining the role of uric acid on incident stroke events are not currently available. Moreover, we found it important to distinguish between total and incident stroke; however, information regarding incidence versus mortality was not readily available for each study. We agree that this additional information would have been useful in framing the previous literature. In conclusion, we agree with Dr Kawada that further work is necessary to understand the role of uric acid in risk of ischaemic stroke and the potential for developing novel cost-effective interventions.