Type IIa Hypercholesterolemia Research Articles

Portacaval shunt (PCS) in type IIa hypercholesterolemia; results from three cases: 21

1) clinical and biological tolerances were good (no hepatic nor cerebral abnormality); cutaneous xanthomas slowly decreased. 2) cholesterolemia decreased (pre-operative levels: respectively 20.6 - 23.2 and 25.8 mmo1/1; post-operative levels: 10.3, 15.5 and 12.9 mmo1/1. 3) insulin and glucagon levels progressively increased (present basal insulin level: 20 μU/ml, glucagon: 500 pg/ml in case 1);results were normal in the 3rd case 2 months after shunt (insulin: 6 μU/ml, glucagon: 34 pg/ml). 4)in case 2, PCS thrombosed during the post-operative period; 18 months later a mesoiliac shunt was as efficient as PCS. 5) in cases 1 and 2 coronarography showed no change of coronary lesions, however; stabilization might be considered as favourable. 6) a diet low in lipids and cholesterol, inefficient before PCS became indispensable in the post-operative period. An increase of 30% of blood cholesterol occurred when the patient returned on a free diet. Continuous noctural gastric drip feeding (with a follow-up of 12 months in case 1) did not give better results than a well controlled diet. 7) a decrease of blood cholesterol during total parenteral feeding in the pre-operative period was a good index of the success of the PCS in the 3 cases.

Clinical experience with the soybean protein diet in the treatment of hypercholesterolemia1–3

The efficacy of the total substitution of animal protein with a textured soybean protein in hypercholesterolemic individuals was assayed in 42 in-patients and 18 out-patients. The in-patients studied followed one of three different crossover protocols: in protocol A, the soybean diet was compared with a standard low lipid diet; protocol B compared two soybean diets, one with added cholesterol, one without; and protocol C compared a soybean diet containing a high P/S fatty acid ratio to one with a low P/S ratio. In all three protocols, the soybean regimen provided valid and reproducible hypocholesterolemic effects that were not modified by the addition of cholesterol. P/S variations appeared, however, to modify the final effect: soybean definitely had a decreased effectiveness with a low P/S (0.1 ) regimen. The overall plasma cholesterol changes in the 42 in-patients after 3 weeks on the different soybean diet protocols was —20%. Patients with type IIA and IIB hypercholesterolemia provided almost equivalent results, whereas patients with mixed phenotypes (IIB-III) appeared somewhat more sensitive to the dietary effect. Cholesterol decreased mostly in the low density lipoprotein fraction, but some very low density lipoprotein changes were also noted upon variation of the P/S ratio. The out-patients studied provided less satisfactory results, possibly due to the difficulty of adequately complying with the diet. These studies indicate that treatment with the soybean diet is an effective regimen for inducing a significant cholesterol reduction in type II patients refractory to standard low lipid regimens.

Biliary lipid secretion in hypercholesterolemia.

A report on the effects of primary bile acid ingestion alone or in combination with plant sterols on serum cholesterol levels, biliary lipid secretion, and bile acid metabolism. Biliary bile acid and cholesterol secretion were measured in four patients with type IIa hypercholesterolemia before and after randomized treatment periods. During these periods either a bile acid mixture (cholic-chenodeoxycholic 2:1, a proportion similar to that endogenously synthesized in health), at a level of 20 mg/kg, or the same mixture plus sitosterols, 200 mg/kg, was fed. Serum cholesterol and the cholesterol saturation of fasting-state bile was also measured. Pretreatment biliary lipid secretion was within normal limits. Bile acid kinetic measurements were also recorded before treatment and showed that cholic acid synthesis was disproportionately decreased relative to that of chenodeoxycholic acid, a finding previously reported by others. Administration of the bile acid mixture increased biliary bile acid secretion in 3 of 4 patients, but did not influence biliary cholesterol secretion. The combination of sitosterol-bile acid, however, caused a relative decrease in cholesterol secretion in bile, and fasting-state bile became unsaturated in all patients. No change in fecal neutral sterol excretion occurred during the beta-sitosterol-bile acid regimen, suggesting that simultaneous bile acid feeding blocks the compensatory increase in cholesterol synthesis known to be induced by beta-sitosterol feeding in hypercholesterolemic patients. Serum cholesterol levels also fell modestly during the sitosterol-bile acid regimen, the decrease averaging 15%. We conclude that the abnormally low rate of bile acid synthesis in patients with type IIa hyperlipoproteinemia does not influence biliary lipid secretion; that increasing the input of the two primary bile acids into the enterohepatic circulation does not increase biliary cholesterol secretion or lower serum cholesterol levels in such patients; and that the usual increase in cholesterol synthesis induced by beta-sitosterol feeding does not occur if bile acids are administered simultaneously.

Regulation of cholesterol synthesis in the hyperlipoproteinaemias — Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia

A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.

Familial hyper-HDL-(α)-cholesterolemia

In one family the mother, two children and a maternal aunt showed a hypercholesterolemic state characterized by a unusually high percentage of cholesterol in ultracentrifugally-recovered HDL-(α)-LP. An intensely stained α-band was present in all these subjects both in plasma and in ultracentrifugal fraction, with d > 1063. Symptoms or signs due to the hypercholesterolemic state were not present. The father was affected by Type IIA hypercholesterolemia. This lipid defect was also present in one of the two children.