title: Lipoprotein metabolism in patients with severe sepsis.
abstract: OBJECTIVE
  Lipoproteins have been implicated to play a role in innate immunity. Changes in lipoprotein levels have been reported in a variety of inflammatory disorders. Not much is known about lipoprotein metabolism in patients with severe sepsis. We conducted an ancillary study in a multiple-center phase III sepsis trial to investigate the dynamics of plasma lipoproteins in patients with severe sepsis.
  
  
  METHODS
  Prospective analysis in patients meeting criteria for severe sepsis as part of a multiple-center sepsis study (KyberSept) with antithrombin III (Kybernin P).
  
  
  METHODS
  University hospital intensive care unit.
  
  
  METHODS
  Seventeen patients were included in the study.
  
  
  METHODS
  Randomized patients received a loading dose of 6000 IU of antithrombin III (Kybernin P) or placebo followed by a 96-hr continuous infusion of 250 IU/hr antithrombin III (Kybernin P) or placebo. In each patient, serial blood samples for total cholesterol, lipoprotein cholesterol, triglycerides, apolipoprotein A-1, apolipoprotein B, and C-reactive protein determination as well as clinical data were collected over 28 days.
  
  
  RESULTS
  Plasma cholesterol levels rapidly decreased from 2.67 +/- 2.02 mmol/L on day 0 to a nadir of 1.41 +/- 0.70 mmol/L on day 3, followed by a slow increase to 4.18 +/- 1.94 mmol/L on day 28. High-density lipoprotein (HDL) cholesterol concentrations decreased rapidly from 0.84 +/- 0.92 mmol/L to a nadir of 0.42 +/- 0.35 mmol/L on day 3, to show a slow increase during the following 4 wks to 0.84 +/- 0.42 mmol/L. The low-density lipoprotein (LDL) cholesterol concentrations were already low (0.94 +/- 0.81 mmol/L) at study entry, to show a progressive increase to subnormal values (2.01 +/- 0.94 mmol/L) at 4 wks. Nadir and recovery lipoprotein concentrations were significantly different (paired Student's t-test, p <.05). A significant correlation was found between HDL cholesterol and apolipoprotein A-1 (r =.714, p <.05) and between LDL cholesterol and apolipoprotein B (r =.733, p <.05). There was no statistical difference in lipoprotein concentrations either between survivors and nonsurvivors or between patients receiving antithrombin III or placebo. Serum amyloid A was a major apoprotein (45%) in HDL at the start of the sepsis and was slowly replaced by apolipoprotein A-1 during recovery. A positive correlation was found between plasma C-reactive protein concentrations and serum amyloid A concentrations in HDL (r =.684, p <.05). No other relevant correlations were found between inflammatory and lipoprotein parameters.
  
  
  CONCLUSIONS
  In patients with severe sepsis, lipoprotein concentrations rapidly change and can be reduced to 50% of recovery concentrations. The pattern of early rapid decline is found primarily in the HDL and a slow recovery in both HDL and LDL fractions. The correlation between apolipoprotein and lipoprotein cholesterol concentrations suggests a decline in lipoprotein particles. During severe sepsis, HDL is shifted to acute phase HDL, which is enriched in serum amyloid A and depleted of cholesterol and apolipoprotein A-1. Lipoprotein concentrations are unable to discriminate between survivors and nonsurvivors.
authors.affiliation: Department of Intensive Care and Clinical Toxicology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Henk J
authors.initials: HJ
authors.lastname: van Leeuwen
authors.forename: Eric C J M
authors.initials: EC
authors.lastname: Heezius
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.forename: Jan
authors.initials: J
authors.lastname: Verhoef
authors.forename: Kok P M
authors.initials: KP
authors.lastname: van Kessel
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001055:Apolipoproteins B / Q000378:metabolism*; D001424:Bacterial Infections / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D007009:Hypolipoproteinemias / Q000378:metabolism* / Q000382:microbiology*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012720:Severity of Illness Index; D016019:Survival Analysis; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D000990:Antithrombin III; D002097:C-Reactive Protein; D002784:Cholesterol