Evidence map›Paper›PMID 42098711›Full record

ArticleLipids in health and disease2026

Associations of ANGPTL3/4/8 proteins and complexes with heart failure and heart failure mortality.

Günther Silbernagel, Ann-Cathrin Maas, Hongxia Li, Deven Lemen, Yan Q Chen, Eugene Y Zhen, Yi Wen, Marcus E Kleber, Graciela Delgado, Angela P Moissl and 4 more

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In one paragraph

Article in Lipids in health and disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Günther Silbernagel *Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, 8010, Austria.
Ann-Cathrin Maas *Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, 8010, Austria.
Hongxia LiLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Deven LemenLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Yan Q ChenLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Eugene Y ZhenLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Yi WenLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Marcus E Kleber1st Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
Graciela Delgado1st Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
Angela P Moissl1st Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
Winfried MärzMedical Clinic III (Cardiology, Pneumology, Angiology), Heidelberg University, Im Neuenheimer Feld 410, Heidelberg, 69120, Germany.
Alexander NiessnerDepartment of Medicine II, Clinical Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, 1090, Austria.
Hubert ScharnaglClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerpl 15, Graz, 8036, Austria.
Robert J KonradLilly Research Laboratories, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA. konrad_robert@lilly.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAngiopoietin-like 3/4/8 (ANGPTL3/4/8) proteins play critical roles in modulating lipid metabolism through calorically sensitive and tissue-specific regulation of lipoprotein lipase (LPL) activity via formation of ANGPTL3/8 and ANGPTL4/8 complexes. ANGPTL3/4/8 proteins are also associated with cardiovascular risk. Circulating levels of ANGPTL3, ANGPTL4/8, and C-terminal domain-containing ANGPTL4 (CD-ANGPTL4) have been associated with overall cardiovascular mortality. In this study, we investigated the associations of ANGPTL3/4/8 proteins and complexes with heart failure (HF) and HF death.

methodsWe studied 2,394 participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort of patients referred for coronary angiography. HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) were diagnosed at baseline. There was a follow-up period with a median (interquartile range) duration of 9.80 (8.75-10.40) years. ANGPTL3/4/8 proteins and complexes were measured at baseline using dedicated immunoassays, and their serum concentrations were compared to HF data.

resultsThere was an inverse association of ANGPTL3/8 with the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). ANGPTL3 was positively associated with NT-proBNP, HFpEF, and the New York Heart Association (NYHA) functional class. ANGPTL4/8 was positively associated with HFrEF, HFpEF, and NT-proBNP and was inversely associated with the left ventricular ejection fraction (LVEF). CD-ANGPTL4 was positively associated with the NYHA functional class, HFrEF, HFpEF, and NT-proBNP and was inversely associated with LVEF. A total of 101 participants died from HF. ANGPTL3/8 and ANGPTL4/8 were not associated with HF mortality. In contrast, ANGPTL3 and especially CD-ANGPTL4 were positively associated with HF death.

conclusionsWe found positive associations of ANGPTL3 and CD-ANGPTL4 with HF and HF mortality. Of particular interest, serum levels of CD-ANGPTL4 demonstrated positive associations with HFrEF, HFpEF, NT-proBNP, and NYHA functional class and an inverse association with LVEF. CD-ANGPTL4 also demonstrated the strongest positive association with HF mortality. The explanation for these associations is not currently apparent. Further investigation will be required to understand more fully the possible biochemical mechanisms that may be responsible for these associations.

Indexed as

Angiopoietin-Like Protein 4Angiopoietin-like ProteinsHeart FailurePeptide HormonesAgedAngiopoietin-Like Protein 3Angiopoietin-Like Protein 8BiomarkersFemaleHumansMaleMiddle AgedNatriuretic Peptide, BrainPeptide FragmentsStroke VolumeAngiopoietin-Like Protein 3Angiopoietin-Like Protein 4Angiopoietin-Like Protein 8Angiopoietin-like ProteinsANGPTL3 protein, humanANGPTL4 protein, humanANGPTL8 protein, humanBiomarkersNatriuretic Peptide, BrainPeptide FragmentsPeptide Hormonespro-brain natriuretic peptide (1-76)ANGPTL3ANGPTL4/8CD-ANGPTL4Heart failureMortality

Identifiers

PMID42098711
PMCPMC13317271

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