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

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.

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.

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.

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