High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P <_ 0.003) and reclassification (P < 0.0001) over a multivariable model. However, the risk of CVM related to high UA (>_5.5 mg/dL, top tertile) was much lower in the subjects with HR _median [2.09 (95% CI 1.75–2.51)]. In the participants stratified by HR tertile, the risk related to hyperuricaemia was 2.38 (95% CI 1.82–3.10) in people with HR >_76 b.p.m. and was 1.24 (95% CI 0.92–1.67) in those with HR <66 b.p.m. Similar results were obtained in the hypertensive patients, in the participants >_65 years, and in the subjects not taking beta-blockers. Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.