Background:Albuminuria predicts adverse events in heart failure with preserved ejection fraction. No therapies to date have reduced albuminuria in heart failure with preserved ejection fraction.Methods and Results:We analyzed 1175 participants from the Americas from the TOPCAT study (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) with urinary albumin:creatinine ratio (UACR) measurements at baseline. We examined the association of UACR with the primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) and its individual components, all-cause mortality, and several safety end points using multivariable-adjusted Cox regression. We evaluated whether spironolactone reduced albuminuria at the 1-year visit in a subpopulation (N=744). Thirty-five percent had microalbuminuria, 13% had macroalbuminuria, and 80% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Increasing UACR was associated with male sex, higher systolic blood pressure, diabetes mellitus, and renal dysfunction. Macroalbuminuria (hazard ratio, 1.67; 95% CI, 1.22–2.28) and microalbuminuria (hazard ratio, 1.47; 95% CI, 1.15–1.86) were independently associated with the TOPCAT primary end point (compared with normoalbuminuria). Adjusting for placebo response, spironolactone reduced albuminuria by 39% in all participants at the 1-year visit compared with baseline (geometric mean ratio, 0.61; 95% CI, 0.49–0.77) and by 76% (geometric mean ratio, 0.24; 95% CI, 0.10–0.56) among those with macroalbuminuria. Reducing UACR by 50% was independently associated with a reduction in heart failure hospitalization (hazard ratio, 0.90; P=0.017) and all-cause mortality (hazard ratio, 0.91; P=0.019). The change in UACR was significantly associated with change in systolic blood pressure (P=0.001).Conclusions:In TOPCAT, albuminuria was independently associated with worse cardiovascular outcomes. Spironolactone significantly reduced albuminuria compared with placebo. Reducing albuminuria was independently associated with improved outcomes.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

中文翻译：

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蛋白尿的预后价值及螺内酯对射血分数保留的心力衰竭的影响


背景：白蛋白尿可预测射血分数保留的心力衰竭的不良事件。迄今为止，还没有任何治疗方法能够减少射血分数保留的心力衰竭患者的白蛋白尿。方法和结果：我们分析了 TOPCAT 研究（用醛固酮拮抗剂治疗保留心脏功能的心力衰竭）中来自美洲的 1175 名参与者的尿白蛋白：肌酐比（ UACR）基线测量。我们使用多变量调整的 Cox 回归检查了 UACR 与主要结局（心血管死亡、心搏骤停或心力衰竭住院治疗）及其各个组成部分、全因死亡率和几个安全终点的关联。我们评估了亚群 (N=744) 在 1 年访视时是否可以减少螺内酯的蛋白尿。 35% 的人患有微量白蛋白尿，13% 的人患有大量白蛋白尿，80% 的人正在接受血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂。 UACR 增加与男性、收缩压升高、糖尿病和肾功能障碍相关。大量白蛋白尿（风险比，1.67；95% CI，1.22-2.28）和微量白蛋白尿（风险比，1.47；95% CI，1.15-1.86）与 TOPCAT 主要终点独立相关（与正常白蛋白尿相比）。调整安慰剂反应后，与基线相比，螺内酯在 1 年访视时使所有参与者的蛋白尿减少了 39%（几何平均比，0.61；95% CI，0.49–0.77）和 76%（几何平均比，0.24；95） % CI, 0.10–0.56) 存在大量白蛋白尿的患者。将 UACR 降低 50% 与心力衰竭住院率（风险比，0.90； P = 0.017）和全因死亡率（风险比，0.91； P = 0）的减少独立相关。019）。 UACR 的变化与收缩压的变化显着相关（ P =0.001）。结论：在 TOPCAT 中，蛋白尿与较差的心血管结局独立相关。与安慰剂相比，螺内酯显着减少蛋白尿。减少蛋白尿与改善结果独立相关。临床试验注册：URL：https://www.clinicaltrials.gov。唯一标识符：NCT00094302。