Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota.
J Am Coll Cardiol. 2014 May 20;63(19):2016-25. doi: 10.1016/j.jacc.2014.02.581. Epub 2014 Mar 26.
This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).
In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.
A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.
In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p < 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p < 0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44 ± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to 2.75), and 15 ± 2% with BNP ratio of ≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survival was confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNP clinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio of ≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p = 0.54) with BNP ratio of <2 (HR: 0.68; 95% CI: 0.52 to 0.89; p = 0.003) or BNP ratio of >2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).
In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.
本研究旨在确定血清 B 型利钠肽（BNP）激活与主动脉瓣狭窄（AS）诊断后生存之间的关系。
在 AS 中，BNP 水平与临床结局之间的联系存在争议。未能考虑到男女 BNP 范围随年龄正常变化，未使用硬性终点（生存），以及未纳入大量患者，导致了这种不确定性。
在同一次医疗过程中，进行了前瞻性测量 BNP 水平和多普勒超声心动图 AS 评估的计划。BNP 比值（测量的 BNP/特定年龄和性别的最大正常 BNP 值）>1 定义为 BNP 临床激活。
在 1953 例至少中度 AS（主动脉瓣面积 1.03 ± 0.26 cm²；平均梯度 36 ± 19 mm Hg）的连续患者中，中位 BNP 水平为 252 pg/ml（四分位距：98 至 592 pg/ml）；BNP 比值 2.46（四分位距 1.03 至 5.66）；射血分数（EF）为 57% ± 15%，60%的患者有症状。在调整所有生存决定因素后，BNP 临床激活（BNP 比值>1）独立预测诊断后的死亡率（p<0.0001；危险比[HR]：1.91；95%置信区间[CI]：1.55 至 2.35），并为生存预测模型提供了增量能力（p<0.0001）。正常 BNP 水平的 8 年生存率为 62% ± 3%，BNP 比值为 1 至 2 的为 44% ± 3%（调整后的 HR：1.49；95%CI：1.17 至 1.90），BNP 比值为 2 至 3 的为 25% ± 4%（调整后的 HR：2.12；95%CI：1.63 至 2.75），BNP 比值≥3 的为 15% ± 2%（调整后的 HR：2.43；95%CI：1.94 至 3.05）。这一与生存的强烈关联在 EF 正常的无症状患者中得到了证实（调整后的 HR：BNP 临床激活为 2.35 [95%CI：1.57 至 3.56]，BNP 比值为 1 至 2 的为 2.10 [95%CI：1.32 至 3.36]，BNP 比值为 2 至 3 的为 2.25 [95%CI：1.31 至 3.87]，BNP 比值≥3 的为 3.93 [95%CI：2.40 至 6.43]）。主动脉瓣置换术与 BNP 比值<2（HR：0.68；95%CI：0.52 至 0.89；p=0.003）或 BNP 比值>2（HR：0.56；95%CI：0.47 至 0.66；p<0.0001）同样具有较高的生存改善边际相关。
在这一系列大型 AS 患者中，BNP 临床激活与长期死亡率的增加呈正相关，且独立于所有基线特征。即使在无症状患者中，随着 BNP 临床激活水平的升高，死亡率也更高，这强调了在管理 AS 患者时，对 BNP 水平进行适当临床解读的重要性。
