Association between serum sulfatide and carotid intima media thickness in patients with familial hypercholesterolemia.

Gang Li,Rui Hu

doi:10.1007/s10719-014-9555-5

Abstract

There is a positive association between sulfatide and atherosclerosis in an animal model for human familial hypercholesterolemia. Carotid intima–media thickness (IMT) is thought to be a marker of atherosclerosis in humans. We investigated the relationship between sulfatide and carotid IMT in heterozygous familial hypercholesterolemia (FH) patients. Thirty-five genetically-verified heterozygous patients with FH and 34 healthy controls were recruited into our study. We measured serum sulfatide levels, the carotid IMT, and conventional cardiovascular risk factors including obesity parameters, blood pressure, fasting blood glucose, and lipid profiles. Subjects with heterozygous FH had significantly elevated serum sulfatide, elevated total cholesterol, low-density lipoprotein cholesterol, and increased carotid IMT compared with control subjects. In patients with FH, univariate analysis showed that serum sulfatide was significantly correlated with carotid IMT. Multiple linear regression analysis indicated that serum sulfatide was the only independent predictor of carotid IMT in patients with FH. Patients with heterozygous FH had significantly higher carotid IMT and the level of serum sulfatide was independently associated with atherosclerotic progression. (R: 0.720, R2: 0.503, p < 0.001).

Highlights

Sulfatides are esters of sulfuric acid with galactosylceramides at C3 of the galactosyl residue, that are widely distributed in various animal organs and sera, including humans [1]
We investigated the association between sulfatide levels and carotid intima–media thickness (IMT) in familial hypercholesterolemia (FH) subjects who had no major cardiovascular risk factors except hypercholesterolemia, in order to confirm the possible association between sulfatides and atherosclerosis
We have found that serum sulfatide level is significantly and independently associated with increased IMT in familial hypercholesterolemia patients, even after controlling for other atherosclerosis risk factors

Summary

Introduction

Sulfatides are esters of sulfuric acid with galactosylceramides at C3 of the galactosyl residue, that are widely distributed in various animal organs and sera, including humans [1]. Using an animal model for human FHWHHL (Watanabe hereditable hyperlipidemic) rabbits, they did a series of experiments comparing normal and WHHL rabbits, and revealed that sulfatides, the major glycosphingolipids in serum lipoproteins, are markedly elevated in WHHL rabbits [2] and accumulated in atheromatous plaques in the aortae of WHHL rabbits [3], which suggested sulfatides maybe take part in the progress of atherosclerosis, even CVD (cardiovascular disease). We subsequently found a close correlation between low levels of serum sulfatides and a high risk of CVD in patients with end-stage renal failure. The findings suggested that sulfatides maybe a novel biomarker predicting the incidence of CVD in patients with end-stage renal failure [4]. Sulfatides may be possibly associated with atherosclerosis in humans. We investigated the association between sulfatide levels and carotid IMT in FH subjects who had no major cardiovascular risk factors except hypercholesterolemia, in order to confirm the possible association between sulfatides and atherosclerosis

Method

Results

Discussion