Lowering Uric Acid May Improve Prognosis in Patients With Hyperuricemia and Heart Failure With Preserved Ejection Fraction
Authors: Nishino Masami , Egami Yasuyuki , Kawanami Shodai , Sugae Hiroki , Ukita Kohei , Kawamura Akito , Nakamura Hitoshi , Matsuhiro Yutaka , Yasumoto Koji , Tsuda Masaki , Okamoto Naotaka , Matsunaga‐Lee Yasuharu , Yano Masamichi , Tanouchi Jun , Yamada Takahisa , Yasumura Yoshio , Tamaki Shunsuke , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Sotomi Yohei , Nakatani Daisaku , Hikoso Shungo , Sakata Yasushi , Sato Taiki , Seo Masahiro , Watanabe Tetsuya , Yamada Takahisa , Hayashi Takaharu , Higuchi Yoshiharu , Masuda Masaharu , Asai Mitsutoshi , Mano Toshiaki , Fuji Hisakazu , Masuda Daisaku , Tamaki Shunsuke , Nagai Yoshiyuki , Yamashita Shizuya , Sairyo Masami , Nakagawa Yusuke , Abe Haruhiko , Ueda Yasunori , Matsumura Yasushi , Nagai Kunihiko , Yano Masamichi , Nishino Masami , Tanouchi Jun , Arita Yoh , Hasegawa Shinji , Ishizu Takamaru , Ichikawa Minoru , Takano Yuzuru , Rin Eisai , Shinoda Yukinori , Tachibana Koichi , Hoshida Shiro , Izumi Masahiro , Yamamoto Hiroyoshi , Kato Hiroyasu , Nakatani Kazuhiro , Yasuga Yuji , Nishio Mayu , Hirooka Keiji , Yoshimura Takahiro , Yasuoka Yoshinori , Tani Akihiro , Okumoto Yasushi , Makino Yasunaka , Onishi Toshinari , Iwakura Katsuomi , Kijima Yoshiyuki , Kitao Takashi , Kanai Hideyuki , Shioyama Wataru , Fujita Masashi , Harada Koichiro , Kumada Masahiro , Nakagawa Osamu , Araki Ryo , Yamada Takayuki , Nakagawa Akito , Yasumura Yoshio , Sato Taiki , Sunaga Akihiro , Oeun Bolrathanak , Kida Hirota , Sotomi Yohei , Dohi Tomoharu , Nakamoto Kei , Okada Katsuki , Sera Fusako , Kioka Hidetaka , Ohtani Tomohito , Takeda Toshihiro , Nakatani Daisaku , Mizuno Hiroya , Hikoso Shungo , Sakata Yasushi 
Published: September 2022

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.