Decreased plasma phosphatidylcholine/free cholesterol ratio as an indicator of risk for ischemic vascular disease.

Abstract

As part of a population survey and a follow-up study of plasma lipid profiles by high temperature gas-liquid chromatography, we have determined the quantities and relative proportions of all major chemical classes and molecular species of llpids of plasma from 1200 subjects at Visit 2 of the Toronto-McMaster Lipid Research Clinic Prevalence Study. We have compared these values between our 24 subjects with ischemic vascular disease and 73 control subjects matched for age, sex, and plasma total cholesterol and triacylglycerols. The phosphatidylcholine/free cholesterol ratio showed the highest association with ischemic vascular disease of any of over 10 other lipid parameters and all the common risk indicators except high density lipoprotein cholesterol. The phosphatidylcholine/free cholesterol ratio had a reiatlve risk ratio of 20/4 (95% confidence limits, 15/9,23/1) and high density llpoproteln cholesterol, a risk ratio of 23/1 (95% confidence limits, 24/0,19/5) for ischemic vascular disease. The average ratio of phosphatidylcholine/free cholesterol for the ischemic vascular disease group was 1.36 and for the controls 1.51, the population average being 1.50. Plasma high density lipoproteln cholesterol had a significant correlation (R = 0.15) with the phosphatidytcholine/ffee cholesterol ratio in the total population sample. The Increased risk for ischemic vascular disease from a tower phosphatidylchollne/free cholesterol ratio may possibly be explained on the basis of decreased fluidity and stability of the lipoproteins due to a relative oversaturatfon with free cholesterol. (Arteriosclerosis 2: 296-302, July/August 1982) A 1976 review' has concluded that the cause and pathogenesis of atherosclerosis remains unsoived. A number of atherogenic processes, inciuding injury to the artery wall, plasma lipoprotein infiltration, thrombosis, and the cellular and tissue responses appear to complement each other. Studies over an extended period of time have established that elevated plasma cholesterol and triglyceride levels are related to the risk of developing ischemic vascular disease (IVD). 2 -3 Of the commonly measured lipoproteins, the low density lipoproteins (LDL), and, to a lesser extent, trie very low density lipopro- teins {VLDL) are positively associated with increased risk, while high density lipoprotein (HDL) is associated with reduced risk and possible protection against the disease. 4 " 6 Due to the many factors that affect biood lipid levels, individual variations in response to environmental conditions, and the fact that they have continuous unimodal frequency distributions in the population, it is impossible to define clearly the normal and abnormal ranges for plasma lipid and lipoprotein fractions. Their ideal concentrations, therefore, remain undecided but in general it is considered that the lower the level of total LDL and VLDL cholesterol and the higher the level of HDL cholesterol the less the risk of premature IVD. 7B However, the metabolic or biochemical and physiochemicai basis for their role in ...

Lipoprotein distribution and composition in obesity: their association with central adiposity

“…Its importance lies in the hypothesis that an increased free cholesterol content of lipoproteins (relative to phospholipids) is an independent risk factor for coronary heart disease. 43 The mechanism by which this modi®cation could in¯uence the atherogenic process is not known. Speculation presently centres on the possibility that higher free cholesterol could decrease the¯uidity of the outer surface of lipoprotein subfractions thus in¯u-encing their participation in different metabolic processes (lipid exchange, lipolysis and receptor recognition).…”

Plasma phosphatidylcholine/free cholesterol ratio as an indicator for atherosclerosis.

“…25 In conclusion, the present study provides further support for the previously observed association of decreased plasma PC/FC ratios with ischemic vascular disease in humans. 6 Although early work had emphasized the protective effect against atherosclerosis of high phospholipid levels 26 and later the ratio of serum glycerophosphoNpids/free cholesterol had been proposed as an indicator of possible abnormalities in lipoprotein fluidity in disease, 27 there had been no specific measurements of the PC/FC ratios under controlled conditions. Recently Morrisett et al 28 have reported the total phospholipid and free cholesterol weight percentages of the HDL fraction of the C57BR/cdJ and CBA/J mice on a normal diet.…”

“…3 The mechanism of the implied infiltration of tissues by plasma lipids has remained obscure, although plausible theories have been advanced. 45 It has been recently reported 6 that in humans a decreased plasma phosphatidylcholine/free cholesterol ratio shows a higher correlation with ischemic vascular disease than does the plasma total cholesterol, or the high density lipoprotein cholesterol. In the present studies we have determined the plasma total lipid profiles in two inbred strains of mice, one of which develops significantly higher total cholesterol levels and significantly larger atheromatous lesions than the other on a high cholesterol diet.…”

Lipid Disorders in Type 1 Diabetes

“…Such increase in the free cholesterol /lecithin ratio within the peripheral layer of lipoproteins has been shown to raise the risk for cardiovascular events possibly by reducing fluidity and stability of lipoproteins (Kuksis, 1982). Moreover, VLDLs from patients with type 1 diabetes have been shown, in vitro, to induce abnormal response of cellular cholesterol metabolism in human macrophages (Klein et al, 1989).…”