Lowering Uric Acid May Improve Prognosis in Patients With Hyperuricemia and Heart Failure With Preserved Ejection Fraction

Abstract

Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.

Serum uric acid: A risk factor for right ventricular dysfunction and prognosis in heart failure with preserved ejection fraction

“…Multiple studies in HFrEF have shown that UA-lowering treatment with benzbromarone or allopurinol failed to improve clinical outcomes, exercise capacity, quality of life, and left ventricular systolic function ( 47 , 48 ). Research in patients with hyperuricemia and HFpEF showed that UA was a predictor for the composite of all-cause mortality and HF rehospitalization and that lowering UA may improve prognosis ( 49 ). This suggests that UA-lowering therapy might help improve the prognosis of the patient.…”

Development and validation of a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in heart failure preserved ejection fraction (HFpEF) patients

“…In this study, we found that NLR was independently associated with the HFpEF, consistent to the report that NLR might be useful to stratify the risk of patients hospitalized with HFpEF 37 . Moreover, previous studies have revealed elevated UA could lead to in ammation and oxidative stress in vascular endothelial cells 19 , and UA was an independent predictor of adverse outcomes in patients with HFpEF [18][19][20]38 . Lowering UA might have a bene cial effect on the prognosis of patients with hyperuricemia and HFpEF 19 .…”

“…Moreover, previous studies have revealed elevated UA could lead to in ammation and oxidative stress in vascular endothelial cells 19 , and UA was an independent predictor of adverse outcomes in patients with HFpEF [18][19][20]38 . Lowering UA might have a bene cial effect on the prognosis of patients with hyperuricemia and HFpEF 19 . In this study, we found the elevation of UA was a diagnostic predictor for HFpEF, suggesting that UA may be a relevant target for clinical prevention and treatment in HFpEF.…”

“…In addition, it is common that patients with HFpEF have hyperuricemia, and elevated uric acid (UA) has been considered as a marker of in ammatory cytokine activation 17 . Several studies have revealed the correlation of elevated UA level with adverse outcomes of HFpEF [18][19][20] . Moreover, renal dysfunction 21 and liver diseases, such as nonalcoholic fatty liver disease 22 and liver stiffness 23 , were clinical co-morbidities for HFpEF.…”

Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice

“…Hyperuricemia mainly occur in higher primates, including in humans, because the gene encoding urate oxidase is inactivated in higher primates [ 2 ]. Elevated serum uric acid has been found to be associated with adverse outcomes in heart failure patients [ 3 ]. The most common lifestyle risk factor for hyperuricosuria is dietary imbalance, especially consumption of high amounts of fructose, purine meats and beer [ 4 ].…”