Fujihashi Takahide, Sakata Yasuhiko, Nochioka Kotaro, Miura Masanobu, Abe Ruri, Kasahara Shintaro, Sato Masayuki, Aoyanagi Hajime, Yamanaka Shinsuke, Hayashi Hideka, Shiroto Takashi, Sugimura Koichiro, Takahashi Jun, Miyata Satoshi, Shimokawa Hiroaki
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Big Data Medicine Center, Tohoku University, Sendai, Japan.
ESC Heart Fail. 2021 Apr;8(2):1027-1038. doi: 10.1002/ehf2.12765. Epub 2020 Dec 30.
Prognostic impacts of serum uric acid (UA) levels in patients with chronic heart failure (CHF) remain inconclusive, especially for the whole range of serum UA levels.
In the Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) study, we enrolled 4652 consecutive patients with CHF and classified them into four groups based on baseline serum UA levels by the Classification and Regression Tree: G1 (<3.8 mg/dL, N = 313), G2 (3.8-7.1 mg/dL, N = 3070), G3 (7.2-9.2 mg/dL, N = 1018), and G4 (>9.2 mg/dL, N = 251). Mean age was 71 ± 12, 69 ± 12, 68 ± 13, and 69 ± 15 years in G1, G2, G3, and G4, respectively (P < 0.001). During the median follow-up of 6.3 years, in G1, G2, G3, and G4, 111 (35%), 905 (29%), 370 (36%), and 139 (55%) patients died and 79 (25%), 729 (24%), 300 (29%), and 115 (46%) experienced heart failure hospitalization, respectively (both P < 0.001). G1 was characterized by a significantly high prevalence of women as compared with G2, G3, and G4 (59%, 32%, 24%, and 23%, respectively). Serum creatinine levels (0.8 ± 0.4, 0.9 ± 0.4, 1.2 ± 0.6, and 1.4 ± 0.8 mg/dL, respectively), prevalence of atrial fibrillation (34%, 39%, 45%, and 50%, respectively), and diuretics use (36%, 45%, 67%, and 89%, respectively) increased from G1, G2, G3 to G4 (all P < 0.001), while left ventricular ejection fraction decreased from G1, G2, G3 to G4 (59 ± 15, 58 ± 15, 54 ± 15, and 52 ± 17%, respectively, P < 0.001). Multivariable Cox proportional hazards models showed that, as compared with G2, both G1 and G4 had increased incidence of all-cause death [adjusted hazard ratio (aHR) 1.34, 95% confidence interval (CI) 1.08-1.67, P = 0.009; aHR 1.28, 95% CI 1.02-1.61, P = 0.037, respectively] and heart failure admission (aHR 1.39, 95% CI 1.09-1.78, P = 0.008 and aHR 1.35, 95% CI, 1.06-1.71, P = 0.014, respectively). This U-shaped relationship was evident in the elderly patients. Furthermore, abnormal transitions to either higher or lower levels of serum UA from G2 were associated with increased mortality (aHR 1.29, 95% CI 1.06-1.57, P = 0.012; aHR 1.57, 95% CI 1.12-2.20, P = 0.009).
These results demonstrate that serum UA levels have the U-shaped prognostic effects and abnormal transitions to either higher or lower levels are associated with poor prognosis in the elderly patients with CHF.
血清尿酸（UA）水平对慢性心力衰竭（CHF）患者预后的影响尚无定论，尤其是对于整个血清UA水平范围。
在东北地区慢性心力衰竭登记与分析-2（CHART-2）研究中，我们连续纳入了4652例CHF患者，并根据分类回归树将他们按基线血清UA水平分为四组：G1（<3.8mg/dL，N = 313）、G2（3.8 - 7.1mg/dL，N = 3070）、G3（7.2 - 9.2mg/dL，N = 1018）和G4（>9.2mg/dL，N = 251）。G1、G2、G3和G4组的平均年龄分别为71±12、69±12、68±13和69±15岁（P<0.001）。在6.3年的中位随访期内，G1、G2、G3和G4组分别有111例（35%）、905例（29%）、370例（36%）和139例（55%）患者死亡，以及79例（25%）、729例（24%）、300例（29%）和115例（46%）患者发生心力衰竭住院（均P<0.001）。与G2、G3和G4组相比，G1组女性患病率显著较高（分别为59%、32%、24%和23%）。血清肌酐水平（分别为0.8±0.4、0.9±0.4、1.2±0.6和1.4±0.8mg/dL）、心房颤动患病率（分别为34%、39%、45%和50%）以及利尿剂使用情况（分别为36%、45%、67%和89%）从G1、G2、G3到G4组均升高（均P<0.001），而左心室射血分数从G1、G2、G3到G组降低（分别为59±15、58±15、54±15和52±17%，P<0.001）。多变量Cox比例风险模型显示，与G2组相比，G1组和G4组全因死亡发生率均升高[调整后风险比（aHR）1.34，95%置信区间（CI）1.08 - 1.67，P = 0.009；aHR 1.28，95%CI 1.02 - 1.61，P = 0.037]，心力衰竭入院发生率也升高（aHR 1.39，95%CI 1.09 - 1.78，P = 0.008；aHR 1.35，95%CI 1.06 - 1.71，P = 0.014）。这种U型关系在老年患者中很明显。此外，从G2组向更高或更低血清UA水平的异常转变与死亡率增加相关（aHR 1.29，95%CI 1.06 - 1.57，P = 0.012；aHR 1.57，95%CI 1.12 - 2.20，P = 0.009）。
这些结果表明，血清UA水平具有U型预后效应，在老年CHF患者中，向更高或更低水平的异常转变与不良预后相关。
