Paradoxical elevation of LDL apoprotein B levels in hypertriglyceridaemic patients and normal subjects ingesting fish oil.

Twenty-three hypertriglyceridaemic patients treated with 15 g/day of a fish oil concentrate (Maxepa) showed the expected reduction in serum triglyceride concentration but levels of LDL apoprotein B (apoB), measured by radial immunodiffusion, increased significantly. Increases in LDL apoB did not correlate with lipoprotein phenotype or changes in serum triglyceride. Studies in eight normal volunteers demonstrated that the effect of fish oil on LDL apoB was not restricted to hypertriglyceridaemic subjects. In view of the evidence that LDL apoB may be a risk factor for coronary heart disease these findings raise questions regarding the use of fish oil in the treatment of hypertriglyceridaemia.

Long-term effects of intestinal alpha-glucosidase inhibition on postprandial glucose, pancreatic and gut hormone responses and fasting serum lipids in diabetics on sulphonylureas.

Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20-52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 +/- 10% (mean +/- SEM, p less than 0.001), insulin to 61 +/- 10% (p less than 0.01) and gastric inhibitory polypeptide to 45 +/- 8% (p less than 0.001) of control values, increased the enteroglucagon response to 152 +/- 26% (p less than 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p less than 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.

Circulating human C-reactive protein binds very low density lipoproteins.

Native human CRP in solution formed complexes with the abnormal lipoprotein beta-VLDL in serum of patients with type III hyperlipoproteinaemia. CRP also formed complexes in sera from individuals with type IV and type V hyperlipoproteinaemia. The binding was calcium-dependent and inhibitable by free phosphoryl choline. No complexes were demonstrable in sera containing high LDL levels from cases of type IIa hyperlipoproteinaemia. Addition of isolated beta-VLDL, but not of isolated LDL, to acute phase normolipoproteinaemic serum caused the appearance of soluble CRP-lipoprotein complexes. In contrast, addition of an excess of isolated normal VLDL to acute phase serum or to isolated CRP was followed by agglutination (creaming) of the lipoprotein particles. Rabbit CRP, on the other hand, formed soluble complexes both with normal human apoB containing lipoproteins and with the abnormal beta-VLDL. Human CRP complexed with rabbit beta-VLDL but not with normal rabbit serum lipoproteins. These interactions may be important for the role of CRP in health and disease.

Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein.

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.

Contrasting patterns of coronary atherosclerosis in normocholesterolaemic smokers and patients with familial hypercholesterolaemia.

An angiographic comparison was made of the extent and severity of coronary artery disease in 25 patients with heterozygous familial hypercholesterolaemia and 25 normocholesterolaemic patients with coronary artery disease in whom heavy cigarette consumption was the chief risk factor. The patients with familial hypercholesterolaemia were younger and included a much higher proportion of women than the smokers. Significantly more patients with familial hypercholesterolaemia had disease of the main stem of the left coronary artery (eight v none, p less than 0.05) and triple-vessel disease (18 v four, p less than 0.05). Disease affecting only distal vessels occurred in five smokers, whereas all the patients with familial hypercholesterolaemia showed a combination of proximal and distal lesions. These findings suggest that cigarette smoking and familial hypercholesterolaemia predispose to different patterns of coronary atheroma. Early coronary angiography with a view to coronary artery bypass surgery seems desirable in symptomatic patients with familial hypercholesterolaemia because of the common association of this disorder with life-threatening left main-stem disease.

Serum lipids and high density lipoprotein cholesterol in peripheral vascular disease.

Serum lipids and high density lipoprotein (HDL) cholesterol concentrations were measured in 32 patients with peripheral vascular diseases (PVD) and 38 control subjects. Hypertriglyceridaemia (> 1.8 mmol/l) was significantly more common in PVD patients of both sexes than among controls but mean serum triglyceride levels were significantly higher only among males. Hypercholesterolaemia (> 7 mmol/l) was not more common in PVD patients nor did mean serum total cholesterol or HDL cholesterol levels differ significantly from control subjects. The HDL ratio, however, was significantly reduced in both males and females with PVD. These results suggest that expressing the amount of cholesterol carried in HDL in relative terms is a better index of vascular risk than is its absolute concentration. The HDL cholesterol level and the HDL ratio were both significantly lower in controls who smoked than in non-smokers; this may explain the reduced HDL ratio in PVD patients, most of whom were smokers.