BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Eur J Heart Fail. 2018 Mar;20(3):514-522. doi: 10.1002/ejhf.1056. Epub 2017 Nov 30.
Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF.
The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1-Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m ), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004], and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration.
Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.
血清尿酸浓度（SUA）升高与心血管疾病风险增加相关，但这可能是由于未测量的混杂因素所致。我们在 PARADIGM-HF 研究中检查了 SUA 与射血分数降低的心力衰竭（HFrEF）患者结局之间的关系，以及 sacubitril/valsartan 对 SUA 的影响。
使用 Cox 回归分析，在调整了基线预后变量（包括估计肾小球滤过率[eGFR]、利尿剂剂量和 N 末端脑钠肽前体的对数）的情况下，对 8213 例患者按 SUA 的五分位数（Q1-Q5）进行了 SUA 与主要复合终点（心血管死亡或心力衰竭[HF]住院）、其组成部分和全因死亡率之间关系的评估。还评估了每个治疗组中 12 个月时 SUA 从基线的变化。与 Q1（<5.4mg/dL）相比，Q5（SUA≥8.6mg/dL）患者年龄更小（62.8 岁 vs. 64.2 岁），男性更多（88.7% vs. 63.1%），收缩压更低（119mmHg vs. 123mmHg），eGFR 更低（57.4 vs. 76.6mL/min/1.73m ），利尿剂使用更多。较高的 SUA 与主要结局（调整后的危险比）的风险更高相关（Q5 与 Q1 相比，调整后的 HR 为 1.28[95%置信区间（1.09-1.50]，P=0.003），心血管死亡（1.44[1.11-1.77]，P=0.001），HF 住院（1.37[1.11-1.70]，P=0.004）和全因死亡率（1.36[1.13-1.64]，P=0.001）。与依那普利相比， sacubitril/valsartan 在 12 个月时使 SUA 降低了 0.24（0.17-0.32）mg/dL（P<0.0001）。 sacubitril/valsartan 改善了结局，而与 SUA 浓度无关。
在 HFrEF 患者的多变量调整后，血清尿酸浓度是结局恶化的独立预测因子。与依那普利相比， sacubitril/valsartan 降低了 SUA 并改善了结局，而与 SUA 无关。
