Relation between prognostic impact of hyperuricemia and sympathetic overactivation in patients with heart failure.

BACKGROUND: Uric acid (UA), which could provide additional prognostic information in patients with heart failure (HF), can activate sympathetic nerve activity and vice versa, thus creating a vicious cycle in the cardiovascular system. However, it remains unclear whether hyperuricemia (UA>7.0mg/dl) can provide prognostic information independent of sympathetic nerve activity.

METHODS: UA and potential prognostic variables including sympathetic nerve activity using microneurography (MSNA) were evaluated in 139 patients with HF (ejection fraction<45%). Primary composite cardiovascular endpoints included cardiovascular death and hospitalization due to HF. Predictors for outcomes were analyzed using univariate, multivariable, and Kaplan-Meier analyses. To determine whether the negative impact of hyperuricemia on outcomes is homogenous, prognostic impacts of hyperuricemia were compared in subgroups of HF. Ejection fraction was followed for 9 months after MSNA measurement in 102 patients.

RESULTS: During a follow-up period of 1636 days, 54 patients fulfilled the primary composite endpoint of cardiovascular death or HF hospitalization. Patients with hyperuricemia had a higher cardiovascular event rate than those with normouricemia (p=0.006). On multivariable Cox proportional hazard analysis, hyperuricemia, higher MSNA, and β-blocker dose were independent predictors of cardiovascular events. In subgroup analyses, impact of hyperuricemia on outcome was similar in all subgroups except sympathetic nerve activity (interaction, p=0.033). Hyperuricemia had negative impact on cardiovascular event rates (hazard ratio=3.44) in group with higher MSNA (p=0.0002), but not in those with lower MSNA. Additionally, the change in LVEF was also significantly lower in patients who had a higher MSNA burst incidence and hyperuricemia.

CONCLUSION: Hyperuricemia might have detrimental effect on prognosis and cardiac function in HF patients with sympathetic overactivation.