title: Plasma PAI-1 levels are independently related to fatty liver and hypertriglyceridemia in familial combined hyperlipidemia, involvement of apolipoprotein E.
abstract: BACKGROUND
  Familial combined hyperlipidemia (FCHL) is a genetic form of dyslipidemia, which is characterized by an increased cardiovascular risk. The current study was conducted to investigate the relation of endothelial, inflammatory and fibrinolysis markers with the presence of hypertriglyceridemia and fatty liver in FCHL, in order to advance insight in their contribution to the cardiovascular risk profile.
  
  
  METHODS
  Key plasma markers of low-grade inflammation, endothelial dysfunction and fibrinolysis were measured in 38 hypertriglyceridemic FCHL patients and 38 age and sex-matched spouses. The presence of fatty liver was determined with ultrasound.
  
  
  RESULTS
  hsCRP, vWF, PAI-1, tPA and tPA/PAI-1 complex levels were significantly higher in hypertriglyceridemic FCHL patients compared to spouses (p<0.05). Subsequent analyses revealed that these increased levels were confined to FCHL patients with the fatty liver phenotype (n=25). Only PAI-1 and tPA levels were also elevated in the hypertriglyceridemic FCHL patients without fatty liver (n=13). Of interest, 11 hypertriglyceridemic non-FCHL patients with the E2/E2 genotype displayed significantly lower PAI-1 levels when compared to the overall FCHL population (p=0.001), implicating a role for apolipoprotein E in the relation of PAI-1 with plasma triglycerides.
  
  
  CONCLUSIONS
  Markers of fibrinolysis were increased in all hypertriglyceridemic FCHL patients, whereas an increased state of endothelial dysfunction and inflammation was particularly observed in those hypertriglyceridemic FCHL patients who also have fatty liver. These results demonstrate the complex genesis of the unfavourable cardiovascular risk profile that is present in FCHL, and illustrate the potential risk of fatty liver above, and beyond hypertriglyceridemia per se.
authors.affiliation: Department of Internal Medicine, University Hospital Maastricht, The Netherlands. martijn.brouwers@intmed.unimaas.nl
authors.forename: Martijn C G J
authors.initials: MC
authors.lastname: Brouwers
authors.forename: Jose
authors.initials: J
authors.lastname: Govers-Riemslag
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.forename: Jaap
authors.initials: J
authors.lastname: Ten Oever
authors.forename: Monique A L
authors.initials: MA
authors.lastname: Bilderbeek-Beckers
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000097:blood*; D002318:Cardiovascular Diseases / Q000175:diagnosis; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D015228:Hypertriglyceridemia / Q000097:blood*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1