Research Unit on Ageing, AGAPLESION Bethesda Clinic, Ulm, Germany.
Geriatric Center Ulm/Alb-Donau, Ulm, Germany.
ESC Heart Fail. 2022 Jun;9(3):1703-1712. doi: 10.1002/ehf2.13834. Epub 2022 Feb 23.
Available upper reference levels (URLs) in older adults for N-terminal pro brain natriuretic peptide (NT-proBNP), an established biomarker for heart failure, are mainly based on small samples. We aimed to identify NT-proBNP URL in a population-based reference sample of individuals aged ≥65 years.
We analysed established NT-proBNP predictors using quantile regression among 2459 participants of two-independent population-based cohorts located in Germany, the Activity and Function in the Elderly Study (ActiFE, n = 1450) and the Study of Health in Pomerania (SHIP-TREND-0, n = 1009). Based on predictors a reference population of 441 subjects (ActiFE, n = 227; SHIP-TREND-0, n = 214) without history of diabetes, cardiovascular, or pulmonary diseases and with systolic blood pressure (BP) <140 mmHg, diastolic BP ≥60 and ≤90 mmHg, haemoglobin in men ≥14 and ≤18 g/dL and in women ≥12 and ≤16 g/dL, GFR ≥60 mL/min/1.73 m , CRP <5 mg/L, BMI ≥18 and ≤33 kg/m , and hs-cTnI <40 ng/L were built with NT-proBNP median levels and 97.5% quantiles reported stratified by sex and age. In a secondary analysis the URL among 97 SHIP-TREND-0 participants with a left ventricular ejection fraction (LVEF) ≥50 and no diastolic dysfunction were estimated. The median age in the identified reference sample was 70 years, with 41.9% and 40.2% male participants in ActiFE and SHIP-TREND-0, respectively. We observed an age-dependent increment of NT-proBNP levels with higher values in women compared to men. Notably, NT-proBNP levels were >125 ng/L in 165 participants (37.4%), with NT-proBNP URL (97.5% quantiles) equal to 663, 824, 592, and 697 ng/L in men, and 343, 463, 2641, 1276 ng/L in women for ages 65-69, 70-74, 75-79, and 80+ years, respectively. In the secondary analysis with a LVEF ≥50 and no diastolic dysfunction (35 men and 62 women) NT-proBNP levels >125 ng/L were still observed in 38 (39.2%) participants.
This reference sample of apparently healthy asymptomatic older adults showed an age-related increment of NT-proBNP levels with URL markedly higher than the European Society of Cardiology recommended cut-off of 125 ng/L for the diagnosis of heart failure in ambulatory settings. Identifying URL in those ≥80 years remains complex. Our results attempt to provide a frame for the further investigation of age-specific NT-proBNP cut-offs in older adults. Considering the demographic changes, further evaluation of NT-proBNP URL in larger samples of older adults followed by the validation of age-specific cut-off values for the identification of heart failure in those 65 years or older are urgently needed.
目前，用于心力衰竭的生物标志物 N 端脑利钠肽前体（NT-proBNP）的老年人群体的上参考值（URL）主要基于小样本。我们旨在确定一个基于人群的参考样本中≥65 岁个体的 NT-proBNP URL。
我们使用位于德国的两个独立人群队列（年龄和功能研究，ActiFE，n=1450；什未林健康研究，SHIP-TREND-0，n=1009）中的已建立的 NT-proBNP 预测因子，使用分位数回归分析了 2459 名参与者。基于预测因子，我们构建了一个无糖尿病、心血管或肺部疾病史且收缩压（BP）<140mmHg、舒张压≥60mmHg 和≤90mmHg、男性血红蛋白≥14g/dL 和≤18g/dL，女性血红蛋白≥12g/dL 和≤16g/dL、肾小球滤过率（GFR）≥60mL/min/1.73m、C 反应蛋白（CRP）<5mg/L、BMI≥18kg/m 和≤33kg/m、高敏心肌肌钙蛋白 I（hs-cTnI）<40ng/L的 441 名参与者（ActiFE，n=227；SHIP-TREND-0，n=214）的参考人群，报告了按性别和年龄分层的 NT-proBNP 中位数水平和 97.5%分位数。在二次分析中，我们还在 97 名 SHIP-TREND-0 参与者中估计了左心室射血分数（LVEF）≥50 且无舒张功能障碍的 URL。确定的参考样本的中位年龄为 70 岁，ActiFE 和 SHIP-TREND-0 中的男性参与者分别占 41.9%和 40.2%。我们观察到 NT-proBNP 水平随年龄的增加而增加，女性的水平高于男性。值得注意的是，在 165 名参与者（37.4%）中 NT-proBNP 水平>125ng/L，男性 NT-proBNP URL（97.5%分位数）分别为 663、824、592 和 697ng/L，女性分别为 343、463、2641、1276ng/L，年龄分别为 65-69、70-74、75-79 和 80+岁。在次要分析中，LVEF≥50 且无舒张功能障碍（35 名男性和 62 名女性），仍有 38 名（39.2%）参与者的 NT-proBNP 水平>125ng/L。
该参考样本中，明显健康的无症状老年个体的 NT-proBNP 水平随年龄增长而增加，URL 明显高于欧洲心脏病学会推荐的 125ng/L 用于诊断门诊心力衰竭的截断值。确定 80 岁以上人群的 URL 仍然很复杂。我们的研究结果试图为进一步研究老年人特异性 NT-proBNP 截断值提供框架。考虑到人口结构的变化，迫切需要在更大的老年人群体中进一步评估 NT-proBNP URL，随后对这些人群中用于识别心力衰竭的年龄特异性截断值进行验证。
