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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Angiopoietin-Like 4 (ANGPTL4) Protein and Its Relation to Lipids Challenges the Prognostic Performance of B-Type Natriuretic Peptide (BNP) Transcontinentally in Patients with Suspected Coronary Chest Pain, Suggesting Their Combined Use in Risk Prediction

  • Dennis W. T. Nilsen1,2
  • Ricardo A. Leon de la Fuente1,3,4
  • Reidun Aarsetoey1
  • Patrycja A. Naesgaard1
  • Patricio F. Gallo4
  • Silvia Dib Ashur4
  • Trygve Brugger-Andersen1
  • Volker Poenitz1
  • Heidi Grundt2,5
  • Annika Elisabet Michelsen6,7
  • Pål Aukrust6,7,8
  • Harry Staines9
1 more authors
  • Thor Ueland6,7
9 affiliations
  1. 1Department of Cardiology, Stavanger University Hospital, 4068 Stavanger, Norway
  2. 2Department of Clinical Science, University of Bergen, 5021 Bergen, Norway
  3. 3Hospital Papa Francisco, Internal Medicine Program, Salta A4400, Argentina
  4. 4Cardiovascular Center of Salta, Department of Cardiology, Salta A4406BFP, Argentina
  5. 5Department of Respiratory Medicine, Stavanger University Hospital, 4068 Stavanger, Norway
  6. 6Faculty of Medicine, University of Oslo, 0318 Oslo, Norway
  7. 7Oslo University Hospital, Rikshospitalet, Research Institute of Internal Medicine, 0372 Oslo, Norway
  8. 8Oslo University Hospital, Rikshospitalet, Section of Clinical Immunology and Infectious Diseases, 0372 Oslo, Norway
  9. 9Sigma Statistical Services, Balmullo KY160BD, UK
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Abstract

BNP is predominantly synthesized in the ventricular myocardium in response to ventricular distension. ANGPTL4 modulates lipid metabolism, vascular integrity and angiogenesis. Both biomarkers serve as prognostic indicators in acute coronary syndrome (ACS). The purpose of this study is to compare the prognostic weighting of ANGPTL4 with BNP in a cross-continental setting and to assess the former’s association with circulating lipids in patients with suspected coronary chest pain. Patients were recruited in Norway (NOR) and Argentina (ARG) and matched exactly by propensity scoring according to age, sex and previous use of statins, yielding 507 subjects in each group. Cox regression models were fitted for standardized loge ANGPTL4 and loge BNP, respectively, with all-cause mortality within 5 years as the dependent variable. Receiver Operating Characteristic (ROC) analysis was applied for the area under curve (AUC). Death rates were similar: (ARG = 20.1%) and (NOR = 22.7%), p = 0.320. ANGPTL4 and BNP were independently associated with all-cause mortality in each cohort. Concentrations of ANGPTL4 and triglycerides (TG) were higher, and total cholesterol (TC), LDL-C and HDL-C were lower in ARG compared to NOR (each p < 0.001). ANGPTL4 correlated negatively with each lipid fraction and positively with C-reactive protein (CRP) but did not correlate with body mass index (BMI) in the cohorts combined. AUC for ANGPTL4 outperformed BNP in ARG, and the reverse was observed in NOR. However, AUC for ANGPTL4 in the combined cohorts was 0.718 (95%CI 0.680–0.756) and for BNP it was 0.730 (95%CI 0.691–0.769). Their different pathogenic pathways may improve prognostic information, with a pattern that may differ between continents.

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Cite

BibTeXRIS
BibTeX
@article{nilsen2026angiopoietinlike,
  title = {{Angiopoietin-Like 4 (ANGPTL4) Protein and Its Relation to Lipids Challenges the Prognostic Performance of B-Type Natriuretic Peptide (BNP) Transcontinentally in Patients with Suspected Coronary Chest Pain, Suggesting Their Combined Use in Risk Prediction}},
  author = {Dennis W. T. Nilsen and Ricardo A. Leon de la Fuente and Reidun Aarsetoey and Patrycja A. Naesgaard and Patricio F. Gallo and Silvia Dib Ashur and Trygve Brugger-Andersen and Volker Poenitz and Heidi Grundt and Annika Elisabet Michelsen and Pål Aukrust and Harry Staines and Thor Ueland},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219966},
  url = {https://www.mdpi.com/1422-0067/27/21/9966},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Angiopoietin-Like 4 (ANGPTL4) Protein and Its Relation to Lipids Challenges the Prognostic Performance of B-Type Natriuretic Peptide (BNP) Transcontinentally in Patients with Suspected Coronary Chest Pain, Suggesting Their Combined Use in Risk Prediction
AU  - Dennis W. T. Nilsen
AU  - Ricardo A. Leon de la Fuente
AU  - Reidun Aarsetoey
AU  - Patrycja A. Naesgaard
AU  - Patricio F. Gallo
AU  - Silvia Dib Ashur
AU  - Trygve Brugger-Andersen
AU  - Volker Poenitz
AU  - Heidi Grundt
AU  - Annika Elisabet Michelsen
AU  - Pål Aukrust
AU  - Harry Staines
AU  - Thor Ueland
PY  - 2026
DA  - 2026/11/06
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219966
UR  - https://www.mdpi.com/1422-0067/27/21/9966
AB  - BNP is predominantly synthesized in the ventricular myocardium in response to ventricular distension. ANGPTL4 modulates lipid metabolism, vascular integrity and angiogenesis. Both biomarkers serve as prognostic indicators in acute coronary syndrome (ACS). The purpose of this study is to compare the prognostic weighting of ANGPTL4 with BNP in a cross-continental setting and to assess the former’s association with circulating lipids in patients with suspected coronary chest pain. Patients were recruited in Norway (NOR) and Argentina (ARG) and matched exactly by propensity scoring according to age, sex and previous use of statins, yielding 507 subjects in each group. Cox regression models were fitted for standardized loge ANGPTL4 and loge BNP, respectively, with all-cause mortality within 5 years as the dependent variable. Receiver Operating Characteristic (ROC) analysis was applied for the area under curve (AUC). Death rates were similar: (ARG = 20.1%) and (NOR = 22.7%), p = 0.320. ANGPTL4 and BNP were independently associated with all-cause mortality in each cohort. Concentrations of ANGPTL4 and triglycerides (TG) were higher, and total cholesterol (TC), LDL-C and HDL-C were lower in ARG compared to NOR (each p < 0.001). ANGPTL4 correlated negatively with each lipid fraction and positively with C-reactive protein (CRP) but did not correlate with body mass index (BMI) in the cohorts combined. AUC for ANGPTL4 outperformed BNP in ARG, and the reverse was observed in NOR. However, AUC for ANGPTL4 in the combined cohorts was 0.718 (95%CI 0.680–0.756) and for BNP it was 0.730 (95%CI 0.691–0.769). Their different pathogenic pathways may improve prognostic information, with a pattern that may differ between continents.
SN  - 1422-0067
ER  -