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Published on: June 10, 2025
Variability of biomarkers in patients with chronic heart failure and healthy controls
Wouter C Meijers1, A Rogier van der Velde1, Anneke C Muller Kobold2
1Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Insights
Biological variation in heart failure (HF) biomarkers is similar in healthy individuals and HF patients. NT-proBNP and GDF-15 show high variability, while ST2, hsTnT, and galectin-3 have lower variation, aiding accurate interpretation.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Cardiology
Background:
- Biomarkers are crucial for diagnosing and managing heart failure (HF).
- Understanding biological variation is essential for interpreting serial biomarker measurements accurately.
- Previous studies have not comprehensively compared biomarker variation in healthy individuals and HF patients.
Purpose of the Study:
- To determine and compare the biological variation of a wide range of biomarkers in healthy subjects and chronic HF patients.
- To calculate key variation indices, including intraindividual (CVi) and interindividual (CVg) variation, and reference change value (RCV).
- To assess the influence of biomarker levels on variation indices.
Main Methods:
- Measured established (NT-proBNP, hsTnT), novel (galectin-3, ST2, GDF-15), and renal/neurohormonal biomarkers in 28 healthy subjects and 83 HF patients.
- Collected serial measurements over 4 months (healthy) and 6 weeks (HF).
- Calculated analytical (CVa), intraindividual (CVi), and interindividual (CVg) variations, and RCV.
Main Results:
- Biomarker levels differed significantly between HF patients and controls (P < 0.01).
- Variation indices (CVi, RCV) were comparable between healthy individuals and HF patients.
- NT-proBNP and GDF-15 exhibited high CVi and RCV, whereas ST2, hsTnT, and galectin-3 showed lower variation.
Conclusions:
- Biological variation indices are similar in healthy individuals and HF patients across various biomarkers.
- NT-proBNP and GDF-15 demonstrate substantial biological variation, necessitating careful interpretation.
- ST2, hsTnT, and galectin-3 exhibit lower variation, potentially offering more stable indicators in HF management.
Aims:
Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.
Methods And Results:
The biological variability of established biomarkers [NT-proBNP and high-sensitivity troponin T (hsTnT)], novel biomarkers [galectin-3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF-15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa ), intraindividual (CVi ), and interindividual (CVg ) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a 'relevant' change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT-proBNP and GDF-15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi , 15.0; RCV, 42.9%), hsTnT (CVi , 11.1; RCV, 31.4%), and galectin-3 (CVi , 8.1; RCV, 25.0%) had lower indices of variation.
Conclusion:
Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT-proBNP and GDF-15 have substantial variation, with lower variation for ST2, hsTnT, and galectin-3. These data are instrumental in proper interpretation of biomarker levels in HF patients.
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