Triglyceride-rich lipoprotein, remnant cholesterol, and apolipoproteins CII, CIII, and E in patients with schizophrenia

Abstract

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.

Keywords: angiopoietin-like proteins; apolipoproteins; remnant cholesterol; schizophrenia; triglyceride-rich lipoproteins; triglycerides.

Fig. 1

Increased levels of non-HDL-apoCII and apoCIII, and HDL-apoE in patients with SZ. Unadjusted analysis of total (A, D, G), non-HDL (B, E, H), and HDL (C, F, I) levels of apoCII (A–C), apoCIII (D–F) and apoE (G–I) in healthy controls (n = 46) and patients with SZ (n = 110) measured by enzyme-linked immunosorbent assay as described in the Materials and methods. Non-HDL values were determined by subtracting HDL values from total values. Data are median and (interquartile range). ns = non-significant; ∗∗P < 0.01; ∗∗∗P < 0.001; ∗∗∗∗P < 0.0001 versus controls by Mann-Whitney U test. apo, apolipoprotein; HDL, high-density lipoprotein; SZ, schizophrenia.