N-terminal pro brain natriuretic peptide reference values in community-dwelling older adults

Aims: 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.

Methods and results: 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 m² , CRP <5 mg/L, BMI ≥18 and ≤33 kg/m² , 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.

Conclusions: 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.