title: Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients.
abstract: BACKGROUND
  Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear.
  
  
  METHODS
  We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects.
  
  
  RESULTS
  Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16-1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01-1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54-0.90]; p = 0.005, 0.76 [0.61-0.94]; p = 0.012, and 1.30 [1.03-1.62]; p = 0.025, respectively).
  
  
  CONCLUSIONS
  We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Saely
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leiherer
authors.affiliation: Medical Central Laboratories, Feldkirch, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Fraunberger
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Elena
authors.initials: E
authors.lastname: Kinz
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rein
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vonbank
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zanolin
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Malin
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: vivit@lkhf.at.
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
mesh_terms: D000368:Aged; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000097:blood* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins
keywords: Angiopoietin-like protein 4; Biomarkers; Cardiovascular events; Coronary artery disease; Metabolic syndrome; Single nucleotide polymorphisms