Influence of low molecular weight heparin compared to conventional heparin for anticoagulation during haemodialysis on low density lipoprotein subclasses

Abstract

Background: In haemodialysis (HD) patients, low density lipoprotein (LDL) particle distribution is characterized by a higher proportion of more atherogenic dense LDL. Though clinical studies showed favourable effects of low molecular weight (LMW) heparin compared to standard heparin on triglycerides (TG) and cholesterol (CH) in HD patients with hypertriglyceridaemia, it is not known if LMW heparin influences LDL subfraction pattern. Thus, the aim of this pilot study was to investigate if a switch to LMW heparin influences LDL subfractions and apolipoproteins.

Methods: Ten outpatients with fasting TG >230 mg/dl in the chronic HD programme on heparin for anticoagulation (AC) were switched to dalteparin (80 IU/kg body weight as a bolus). Blood samples were drawn for CH, TG, LDL-CH, HDL-CH, apolipoproteins (apo), very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL subclasses at the beginning and after 12 months of therapy. Lipoproteins were isolated by preparative ultracentrifugation. Total LDL were fractionated into six density classes by equilibrium density gradient ultracentrifugation [(density in kg/l): LDL-1 1.019-1.031, LDL-2 1.031-1.034, LDL-3 1.034-1.037, LDL-4 1.037-1.040, LDL-5 1.040-1.044, LDL-6 1.045-1.063]. CH and TG were determined enzymatically, apolipoproteins by turbidimetry.

Results: In eight patients suitable for evaluation cholesterol decreased from 241 to 202 (P<0.05) and TG from 557 to 278 mg/dl (P<0.01), whereas LDL-CH and HDL-CH did not change significantly. A 28.2% decrease of VLDL (P<0.01) and a 19.3% decrease of IDL (P<0.05) paralleled by a significant drop of apoB were observed. Buoyant LDL subclasses increased (LDL-2, +34.3% and LDL-3, +20.3%) whereas dense LDL (LDL-5, -13.4% and LDL-6, -33.1%) decreased (P<0.05 for LDL-6). The ratio of buoyant LDL to dense LDL increased from 0.46+/-0.28 to 0.72+/-0.33 (P<0.05).

Conclusion: In hypertriglyceridaemic HD patients, dalteparin improved metabolism of TG-rich lipoproteins, increased buoyant LDL and decreased potentially atherogenic dense LDL. Preservation of lipoprotein lipase by LMW heparin may be a possible mechanism to explain our findings.