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

Abstract

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 > 7.0 mg/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 b-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.

Hyperuricemia and Its Association With the Severity and Complications of Congestive Heart Failure: A Systematic Review

“…Sympathetic overactivity can also directly produce reactive oxygen species, and hence, both xanthine oxidase and sympathetic overactivity may be interrelated in the pathophysiology of CHF. They concluded that hyperuricemia in a CHF patient in a hyperadrenergic state may be an ominous predictor of worse outcomes [ 27 ]. Thus, beta blockers are indispensable in the treatment of heart failure, and future trials need to be carried out to establish the efficacy of xanthine oxidase inhibitors in the treatment of congestive heart failure.…”

Sympathetic overactivation predicts body weight loss in patients with heart failure

“…All parameters were obtained in resting patients who were awake and in a supine position, as previously described (Joho et al, 2012;Ushijima et al, 2014;Joho et al, 2019). Blood pressure was serially recorded using noninvasive tonometry (Jentow 7700, Colin, Komaki, Japan).…”

“…Blood pressure was serially recorded using noninvasive tonometry (Jentow 7700, Colin, Komaki, Japan). Multiunit recordings of efferent postganglionic sympathetic nerve activity to skeletal muscle regions were captured via a microelectrode inserted directly into the peroneal nerve posterior to the fibular head (Joho et al, 2012;Ushijima et al, 2014;Joho et al, 2019). MSNA is a sympathetic neural activity innervating muscle vascular beds that regulate systemic vascular resistance in order to directly contract arterioles.…”