Lipoprotein metabolism in patients with severe sepsis

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Abstract
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. Prospective analysis in patients meeting criteria for severe sepsis as part of a multiple-center sepsis study (KyberSept) with antithrombin III (Kybernin P). University hospital intensive care unit. Seventeen patients were included in the study. 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. 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. 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.