Abstract-LDL particle sizes and Apo E phenotypes were determined in 212 subjects of whom 51 had angina. LDL diameter was significantly less in subjects with an ⑀2 allele (24.76Ϯ0.08 vs 24.94Ϯ0.02 nm, Pϭ0.02), and this was evident for both E2/E3 (24.77Ϯ0.09 nm) and E2/E4 (24.69Ϯ0.08 nm) phenotypes. Although there was a negative relation between LDL diameter and plasma triglyceride, the effect of apo E2 was still evident with adjustment for triglyceride. In multiple regression analysis, the significant determinants of LDL diameter were gender (with females having larger particles than males), body mass index, and the presence (or absence) of E2. HDL particle sizes and compositions were determined on fasting samples and, additionally, 5 and 8 hours after a fat-rich meal for 48 coronary heart disease cases and 49 control subjects. Fasting HDL particle sizes were not related to the presence of E2 but were significantly smaller for subjects possessing an ⑀4 allele (8.09Ϯ0.08 vs 8.39Ϯ0.05 nm, Pϭ0.003) and were negatively related to plasma triglyceride. However, the effect of E4 persisted after adjustment for triglyceride. In a multiple regression analysis, the only significant determinant of fasting HDL diameter was the presence (or absence) of E4 with fasting plasma triglyceride just failing to reach significance (Pϭ0.06). There was a postprandial increase in HDL diameter that was less marked in subjects with coronary heart disease. The postprandial increase in HDL diameter was of sufficient magnitude to result in size reclassification of HDL particles. The influence of E4 was also evident at both postprandial time points. Compositional analysis demonstrated that the increase in HDL diameters postprandially could be attributed to triglyceride enrichment, with an accompanying fall in cholesterol ester content. Phospholipid changes postprandially were biphasic with an initial fall followed by a rise in concentration. The increase in triglyceride content was significantly less in those subjects with angina despite an equivalent rise in plasma triglyceride. The present study demonstrates significant, but different, effects of variation in apo E phenotype on the particle sizes of both HDL and LDL. Such effects were still evident with adjustment for differences in plasma triglyceride and suggests that variation in apo E phenotype exerts effects on lipoprotein particle sizes by mechanisms additional to those dependent on change in plasma triglyceride. Key Words: apo E Ⅲ LDL particle size Ⅲ HDL particle size Ⅲ triglyceride Ⅲ coronary heart disease Ⅲ postprandial T here is considerable evidence that variation in apo E phenotype, dependent on the assortment of ⑀4, ⑀3, and ⑀2 alleles, contributes to the variation in occurrence of coronary heart disease (CHD). Thus the possession of an ⑀4 allele has been associated with the CHD in the European Atherosclerosis Research Study. 1 More severe atheroma was found in the coronary vessels of Alzheimer's patients with an ⑀4 allele than in those without, and elderly Finnish men dying of co...

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1 Vasomotor function of the vascular endothelium was examined in human subcutaneous arteries excised from 8 hypercholesterolaemic and 7 normolipidaemic subjects. 2 Left gluteal skin biopsies were performed under local anaesthesia. Subcutaneous arteries were isolated and two vessels from each subject mounted in separate myographs. A 20 ml fasting blood sample was taken at the time of the biopsy. 3 Hypercholesterolaemic subjects had either never been treated with lipid lowering therapy or therapy had been stopped at least two weeks before the study (n=2). At the time of the study total plasma cholesterol levels (control: 4.6+0.3 vs hypercholesterolaemic: 8.3+0.6 mmol l 71 : P50.01) were signi®cantly elevated in hypercholesterolaemic subjects when compared with controls. 4 Full concentration-response curves to the vasoconstrictor noradrenaline and the vasodilators acetylcholine and substance P were constructed. A single point concentration-response to sodium nitroprusside (10 mM) was also obtained. Dilator responses were obtained in vessels pre-constricted with a submaximal concentration of noradrenaline. Vessels were then incubated for 30 min with either L-or D-arginine (10 mM) and the concentration-response curves to the three dilator agonists repeated in the presence of the amino acid. 5 Maximum relaxation responses to acetylcholine (control vs hypercholesterolaemic: 83.3+6.1% vs 47.4+13.5%; P50.05), but not to substance P or sodium nitroprusside, were dampened in the hypercholesterolaemic group when compared with controls. 3%).7 When results from the two study groups were pooled, the strongest predictor of maximum relaxation obtained to acetylcholine was apolipoprotein A 1 (r=0.67; P=0.001). 8 In conclusion, relaxation responses mediated by the endothelium-dependent agonist acetylcholine, but not by substance P, are impaired in hypercholesterolaemic patients. L-Arginine did not improve the impaired relaxation responses to acetylcholine. We suggest that impaired endothelium-dependent relaxation is speci®c to acetylcholine and not to an abnormal L-arginine-nitric oxide pathway in subcutaneous arteries excised from this study group.