Non-cholesterol sterols in different forms of primary hyperlipemias

Lupattelli, G.; Pirro, M.; Siepi, D.; Mannarino, M.R.; Roscini, A.R.; Vaudo, G.; Pasqualini, L.; Schillaci, G.; Mannarino, E.

doi:10.1016/j.numecd.2010.05.010

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Non-cholesterol sterols in different forms of primary hyperlipemias

Internal Medicine, Angiology and Atherosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Italy

Received 7 February 2010; received in revised form 19 May 2010; accepted 21 May 2010. published online 16 August 2010.
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Abstract

Background and Aims

We investigated the behaviour of non-cholesterol sterols, surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol), in primary hyperlipemias.

Methods and results

We studied 53 patients with polygenic hypercholesterolemia (PH), 38 patients with familial combined hyperlipemia (FCH), and 19 age- and sex-matched healthy control subjects. In all participants, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled to mass spectrometry. To correct for the effect of plasma lipid levels, non-cholesterol sterol concentrations were adjusted for plasma cholesterol (10² μmol/mmol cholesterol). Patients with FCH were more frequently men, and had higher body mass index (BMI), fasting glucose, insulin and HOMA-IR. Lathosterol was higher in FCH than in pH or controls (p < 0.05). Campesterol was significantly lower in FCH (p < 0.05), while no differences were found between pH and controls. Sitosterol displayed higher values in pH compared to FCH (p < 0.001) and controls (p < 0.05). Spearman’s rank correlations showed positive correlations of lathosterol with BMI, waist circumference, HOMA-IR, triglycerides, apoprotein B, and a negative one with HDL-cholesterol. Sitosterol had a negative correlation with BMI, waist circumference, HOMA-IR, triglycerides, and a positive one with HDL-cholesterol and apoprotein AI. Multivariate regression analyses showed that cholesterol absorption markers predicted higher HDL-cholesterol levels, while HOMA-IR was a negative predictor of sitosterol and BMI a positive predictor of lathosterol.

Conclusions

Our findings suggest the occurrence of an increased cholesterol synthesis in FCH, and an increased cholesterol absorption in pH. Markers of cholesterol synthesis cluster with clinical and laboratory markers of obesity and insulin resistance.

Keywords: Polygenic hypercholesterolemia, Familial combined hyperlipemia, Non-cholesterol sterols