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Reference ranges for natriuretic peptides for diagnostic use are dependent on age, gender and heart rate
Ian Loke1, Iain B Squire, Joan E Davies
1Department of Medicine and Therapeutics, Clinical Sciences Building, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
Insights
Plasma natriuretic peptide levels, including N-terminal pro-Atrial (N-ANP), B-type (BNP), and N-terminal pro-B-type (N-BNP), are influenced by age and gender in healthy adults. These factors are crucial for establishing accurate diagnostic reference ranges.
Area of Science:
- Cardiovascular Physiology
- Biomarker Research
- Clinical Diagnostics
Background:
- Plasma natriuretic peptides aid heart failure diagnosis.
- Assay performance varies significantly.
- Age and gender influence peptide levels.
Purpose of the Study:
- To investigate the impact of clinical and echocardiographic factors on N-terminal pro-Atrial (N-ANP), B-type (BNP), and N-terminal pro-B-type (N-BNP) levels.
- To describe these influences within a healthy population.
Main Methods:
- Analyzed 720 healthy individuals (417 men, 303 women) aged 45-80 years.
- Assayed N-ANP, BNP, and N-BNP using in-house immunoluminometric methods.
- Excluded individuals with cardiovascular disease or on medication; all had normal echocardiograms and ECGs.
Main Results:
- Gender and heart rate independently affected all three peptides.
- Women exhibited higher N-ANP, BNP, and N-BNP levels.
- Age influenced N-ANP and N-BNP but not BNP; heart rate inversely correlated with all peptides.
Conclusions:
- Plasma N-ANP, BNP, and N-BNP levels are variably affected by clinical factors in healthy individuals.
- Age and gender significantly influence N-ANP and N-BNP levels, necessitating consideration for diagnostic ranges.
- Assay format and patient covariates like age and gender are critical for accurate interpretation of natriuretic peptide levels.
Background:
Plasma natriuretic peptide levels may be useful in the diagnosis of heart failure. The available natriuretic peptide assays differ markedly in their performance characteristics. In addition, plasma levels are influenced by a number of factors including age and gender.
Aims:
The aim of this study was to describe, in a healthy population, the influence of clinical and echocardiographic parameters on three natriuretic peptide moieties.
Methods:
1360 individuals were screened for the presence of left ventricular systolic dysfunction. We identified a cohort (n=720) of men aged 45-80 years (n=417) and women aged 55-80 years (n=303). None had history of cardiovascular disease or were taking any cardiovascular medication. All had normal echocardiographic and ECG findings. B-type (BNP), N-terminal pro-B-type (N-BNP) and N-terminal pro-Atrial (N-ANP) natriuretic peptides were assayed using in-house immunoluminometric assays.
Results:
Of the considered clinical variables, only gender and heart rate (each P<0.005) were independently associated with levels of all three natriuretic peptides. Plasma levels of N-ANP (15%), BNP (25%) and N-BNP (75%) were higher in women compared to men. An increase in heart rate of 10 bpm corresponded to a reduction of 9% in N-ANP or BNP and a 15% reduction in N-BNP. Each 10 years of age was associated with 16% and 74% increase in ANP and N-BNP levels, respectively, but no increase in plasma BNP. Left ventricular ejection fraction could be assessed in 582 (81%) subjects and correlated positively with N-ANP (r(s)=6.48x10(-3), P<0.001) and BNP (r(s)=2.4x10(-2), P<0.001) but not N-BNP (P=0.405). No parameter of diastolic function was associated with any peptide level.
Conclusions:
In this healthy population, plasma levels of N-ANP, BNP and N-BNP were variably influenced by clinical covariates. While all three peptides were higher in women, only N-ANP and N-BNP were influenced by age. Levels of all peptides were inversely correlated with heart rate. Using this immunoluminometric assay, plasma BNP is not influenced by age, in contrast to N-ANP and N-BNP. In constructing normal ranges for diagnostic use, covariates such as age and gender must be considered, in addition to the format of assay being used.
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