Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease

doi:10.1016/S0021-9150(97)06097-8

Atherosclerosis

Volume 131, Issue 2, June 1997, Pages 161-166

https://doi.org/10.1016/S0021-9150(97)06097-8 Get rights and content

Abstract

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL_2b of large particle size, increased levels of small HDL_3C particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL_2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator.

Introduction

It is now well established that the development of coronary heart disease is associated with elevated plasma concentrations of low density lipoprotein (LDL) and reduced concentrations of high density lipoprotein (HDL). Indeed, the ratio of LDL-cholesterol to HDL-cholesterol has been shown to be one of the strongest predictors of coronary heart disease in asymptomatic subjects and is more than ten times more powerful than the measurement of total plasma-cholesterol 1, 2. Both HDL and LDL, however, consist of mixtures of particles which differ in composition, size and metabolic role. Recent studies have shown that subjects of high coronary risk have low concentrations of a subfraction of HDL of large particle size and rich in apolipoprotein (apo) E (HDL_2b) and also a high concentration of the smaller particles (HDL_3c) compared with control subjects 3, 4, 5.

Few studies, however, have reported on the lipoproteins in patients with peripheral arterial disease (PAD) and these have produced conflicting results 6, 7, 8, 9, 10, 11, 12. The aim of the study reported here was therefore to investigate further and in greater detail the lipoprotein levels in PAD, using a larger number of patients than has been used in most previous investigations. The study included the measurement of levels of HDL subfractions. Since the interconversions of HDL subspecies are associated with the overall transport of cholesterol any changes observed in their distribution may reflect alterations in lipoprotein metabolism in the diseased state. This may therefore provide valuable information on the underlying causes of the disease [13].

Section snippets

Cases

The cases consisted of male patients with lower limb atherosclerosis attending a vascular clinic at the Royal Infirmary of Edinburgh. All patients had symptoms of intermittent claudication according to the Edinburgh Claudication Questionnaire [14]and an ankle brachial pressure index of ≤0.9 in at least one limb. Patients who had critical limb ischaemia, diabetes or severe intercurrent illness including liver disorders, malignancy or epilepsy were excluded. None of the patients were on

Results

Patients with peripheral arterial disease were significantly older than the controls (Table 1) but mean body mass index was similar in both groups. Smoking was positively associated with PAD with a level of significance of P<0.001. However, there was no statistically significant difference in the level of total HDL-cholesterol or in any of the gradient gel HDL subfractions between current smokers and ex-smokers in the patient group or between current smokers and subjects who have never smoked

Discussion

The present study confirms the findings of previously reported investigations that patients with peripheral arterial disease have elevated levels of triglyceride and VLDL-cholesterol compared with healthy control subjects 8, 12while plasma-cholesterol levels were either unchanged [12]or increased 6, 7, 10. In this study, however, the PAD patients had significantly lower levels of LDL-cholesterol than the control subjects in contrast to previous reports that LDL-cholesterol concentrations were

Acknowledgements

The study was funded by a grant from Scotia Pharmaceuticals Ltd. We thank Mrs Kate Watt for skilled technical assistance.

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