A network analysis to compare biomarker profiles in patients with and without diabetes mellitus in acute heart failure
OA Location
Author(s)
Type
Journal Article
Abstract
Aims
It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways.
Methods and results
We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal function (NGAL, KIM-1) (adjusted P-value <0.05). Among patients with diabetes, network analysis revealed that periostin strongly clustered with C-reactive protein and interleukin-6. Furthermore, renal markers (creatinine and NGAL) closely associated with potassium and glucose. These findings were not seen among patients without diabetes.
Conclusion
Patients with AHF and diabetes, compared with those without diabetes, have distinct biomarker profiles. Network analysis suggests that cardiac remodelling, inflammation, and fibrosis are closely associated with each other in patients with diabetes. Furthermore, potassium levels may be sensitive to changes in renal function as reflected by the strong renal–potassium–glucose correlation. These findings were not seen among patients without diabetes and may suggest distinct pathophysiological processes among AHF patients with diabetes.
It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways.
Methods and results
We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal function (NGAL, KIM-1) (adjusted P-value <0.05). Among patients with diabetes, network analysis revealed that periostin strongly clustered with C-reactive protein and interleukin-6. Furthermore, renal markers (creatinine and NGAL) closely associated with potassium and glucose. These findings were not seen among patients without diabetes.
Conclusion
Patients with AHF and diabetes, compared with those without diabetes, have distinct biomarker profiles. Network analysis suggests that cardiac remodelling, inflammation, and fibrosis are closely associated with each other in patients with diabetes. Furthermore, potassium levels may be sensitive to changes in renal function as reflected by the strong renal–potassium–glucose correlation. These findings were not seen among patients without diabetes and may suggest distinct pathophysiological processes among AHF patients with diabetes.
Date Issued
2017-06-21
Date Acceptance
2017-05-18
Citation
European Journal of Heart Failure, 2017, 19 (10), pp.1310-1320
ISSN
1388-9842
Publisher
Wiley
Start Page
1310
End Page
1320
Journal / Book Title
European Journal of Heart Failure
Volume
19
Issue
10
Sponsor
Royal Brompton & Harefield NHS Foundation Trust
National Institute for Health Research
Grant Number
N/A
N/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Acute heart failure
Diabetes
Network analysis
Biomarkers
Periostin
Inflammation
CLINICAL CHARACTERISTICS
PERIOSTIN
ASSOCIATION
PROTECT
ROLOFYLLINE
ANTAGONIST
MORTALITY
OUTCOMES
GLUCOSE
REPAIR
Publication Status
Published