Changes In High-density Lipoprotein Research Articles

Changes in High Density Lipoproteins with High Content of Serum Amyloid A Protein by the Incubation with Polymorphonuclear Leucocytes

Changes in High Density Lipoproteins with High Content of Serum Amyloid A Protein by the Incubation with Polymorphonuclear Leucocytes

Hypertension, changes in high-density lipoproteins and antihypertensive therapy

The risk for development of coronary heart disease (CHD) is related to a number of factors. Among these, both hypertension and various lipid abnormalities have been shown to play an important role. A clear inverse relation between high-density lipoprotein (HDL) cholesterol and CHD has been observed in numerous observational and short studies. Pharmacologic treatment of hypertension has been shown to reduce dramatically some of the sequelae of high blood pressure—renal failure, cerebrovascular accidents and congestive heart failure. However, a consistent reduction in associated CHD has not been demonstrated, and the dissociation between reducing blood pressure and reduction in CHD has not been definitively explained. One of the suggested explanations relates to alterations in blood lipid levels that may be induced by certain antihypertensive agents. Changes in HDL cholesterol levels or other lipid alterations due to antihypertensive therapy could modify the beneficial effects achieved by the direct reduction of blood pressure. If so, antihypertensive agents could be subclassified as atherogenic or antiatherogenic depending on the associated changes in lipid levels. Therefore, the antihypertensive agents of choice for patients whose cholesterol levels are a concern would be those that reduce the CHD risk factor of hypertension without compromising the risk factor associated with a patient's lipid profile.

Apolipoprotein A-I inhibits transformation of high density lipoprotein subpopulations during incubation of human plasma

We have examined the effect of added apolipoprotein A-I (apoA-I) on the changes in high density lipoprotein (HDL) particle size that occur when human plasma is incubated in vitro. In the absence of added apoA-I, incubation of plasma at 37°C resulted in a dramatic increase in HDL particle size. When these incubations contained an inhibitor of LCAT, an additional population of smaller HDL particles was formed. These changes in particle size were even more pronounced when the incubations were supplemented with an artificial triglyceride emulsion, Intralipid. All these changes in HDL particle size were markedly inhibited when incubations were supplemented with apoA-I. Even when the amount of added apoA-I was as little as 4.5% of the endogenous apolipoprotein there was an obvious inhibition of the changes in HDL particle size. The presence of added apoA-I sufficient to increase the plasma concentration by 18% virtually abolished the changes in HDL particle size. This effect did not relate to an inhibition of cholesterol esterification, nor did it appear to depend on an incorporation of the added apoA-I into the HDL.

Effects of alpha- and beta-adrenergic antagonists on plasma apolipoproteins and forearm blood flow in patients with mild hypertension

To study the mechanisms by which adrenergic antagonists affect blood pressure and plasma lipid levels, the effects of alpha-blockade with prazosin were compared with those of beta-blockade with propranolol in 23 normolipidemic, mildly hypertensive patients. Plasma lipoprotein composition, apolipoproteins, and some of the processes involved in lipid synthesis and clearance from plasma were investigated also. Patients entered an eight-week placebo period during which they were free of all antihypertensive medications. They were then randomly assigned under double-blind conditions to treatment with either prazosin (mean dose, 5 mg per day) or propranolol (mean dose, 133 mg per day) for eight weeks. Doses of both drugs were titrated to achieve either a decrease in diastolic blood pressure of 10 mm Hg or more or a reduction of diastolic blood pressure to less than 85 mm Hg, whichever was lower. Total plasma cholesterol decreased by 9 percent during prazosin treatment and increased by 7 percent during propranolol treatment (p <0.005 between treatments). Low-density lipoprotein cholesterol decreased by 12 percent with prazosin and increased by 12 percent with propranolol (p <0.005). Apolipoprotein B decreased by 17 percent with prazosin and increased by 15 percent with propranolol (p <0.005). There were no significant changes in total high-density lipoprotein cholesterol, its subfractions high-density lipoprotein 2 or high-density lipoprotein 3, or in apolipoprotein A 1 and apolipoprotein A 2. Plasma very low-density lipoprotein and low-density lipoprotein triglycerides were not significantly affected by either treatment. Plasma post-heparin lipase activities, which clear triglyceride and high-density lipoprotein cholesterol from plasma, were not altered significantly. Since regional blood flow could affect the clearance of plasma lipoproteins, measurements were taken of forearm blood flow, forearm vascular resistance, and maximal forearm vasodilatory potential during reactive hyperemia. The adrenergic antagonists had no effect on these measurements, nor did they affect cellular cholesterol synthesis as measured by the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in blood mononuclear cells. The results of this study demonstrate differing actions between alpha- and beta-adrenergic antagonism. Alpha-blockade produced significantly lower levels of plasma low-density lipoprotein cholesterol and apolipoprotein B than beta-adrenergic antagonism without changes in high-density lipoproteins.

Alterations in the HDL system after rapid plasma cholesterol reduction by LDL-apheresis

Changes in high density lipoprotein (HDL) subfraction structure and composition were analyzed during and after extracorporeal removal of apo B containing lipoproteins in seven familial hypercholesterolemic (FH) patients. After the apheretic procedure, carried out with dextran-sulfate-cellulose columns, the plasma levels of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and HDL decreased by 72%, 50%, and 19%, respectively. The free cholesterol to esterified cholesterol ratio in plasma increased, with a 26% drop in the lecithin: cholesterol acyl transferase (LCAT) activity. In the ensuing 24 hours, VLDL, HDL, and LCAT activity approached the pretreatment levels. During this phase, possibly as a consequence of increased cholesterol esterification and exchange of cholesteryl esters for triglycerides between HDL and VLDL, HDL 2a particles were detected in plasma. However, these metabolic changes did not result in clearcut modifications in the HDL 2-HDL 3 subfraction distribution. These findings clearly demonstrate that rapid changes in the plasma VLDL-LDL levels affect several processes involved in the HDL metabolism, but confirm that the HDL system, in spite of a considerable plasticity, displays a marked stability of the HDL 2-HDL 3 subfraction distribution.

Lipoprotein catabolism in rats with portacaval anastomosis on various diets

The catabolism of lipoproteins was measured in rats with a portacaval anastomosis and in intact control rats. Radioiodinated rat high density lipoproteins or human low density lipoproteins, the major cholesterol-bearing lipoproteins in rat or man respectively, were injected intravenously into rats. More than 90% of trace amounts of these lipoproteins were removed from plasma of rats with portacaval anastomosis and controls on standard chow at closely similar rates within 24 h. Also, [1251]high density lipoproteins left the plasma at comparable rates in controls and rats with portacaval anastomosis, whether fed with a cholesterol-free chow or a carbohydrate-rich lard chow. These dietary regimens were employed to avoid artifacts through a different development of the body weight in operated and control rats. A standard laboratory chow ad libitum led to weight loss in rats with portacaval anastomosis. Pair-fed with a cholesterol-free chow both groups of rats kept the same weight, but only with a carbohydrate-rich lard chow could the natural weight gain be achieved. In all rats with portacaval anastomosis liver weights were reduced and serum cholesterol decreased by 21–31% with the major change in high density lipoproteins. The findings suggest that cholesterol concentrations are not likely to be lowered in rats with portacaval anastomosis by enhanced lipoprotein catabolism.

Lipoprotein modifications during dietary treatment in patients with primary type V hyperlipoproteinaemia.

Type V hyperlipoproteinaemia is a disorder of lipid transport characterized by the accumulation in serum of chylomicrons and very low density lipoproteins. The purpose of the study was the analysis of serum lipids and lipoproteins by ultracentrifugation in nine patients with primary type V hyperlipoproteinaemia before and during dietary treatment. After 30 days of balanced isocaloric diet mean serum triglycerides fell from 25.4 +/- 15.0 (mean +/- SD) to 2.8 +/- 1.7 mmol l-1. At the same time the chylomicrons and the very low density lipoproteins of flotation rate higher than 100 disappeared from the serum while the remaining very low density lipoproteins maintained unaltered their normal protein-lipid composition. After 30 days the low density lipoproteins increased significantly in concentration (from 1.6 +/- 0.8 to 4.1 +/- 1.1 mmol l-1 cholesterol) and their percentage content of cholesterol and triglyceride was increased and reduced, respectively. The highest concentration of intermediate density lipoprotein cholesterol was observed after 15 days of treatment (1.2 +/- 0.6 mmol l-1. The abnormally low concentrations and the physicochemical properties of the high density lipoproteins remained unchanged throughout the study (from 0.6 +/- 0.2 to 0.8 +/- 0.2 mmol l-1 cholesterol concentration) and no high density lipoproteins two (HDL2) were observed at any time. The effects of this treatment were an increase in low density and marginal change in high density lipoproteins which are considered, respectively, a positive and a negative risk factor for atherosclerosis.

Adrenergic effects on plasma lipoprotein metabolism: Speculation on mechanisms of action

Recently, the effects of alpha-adrenergic and beta-adrenergic antagonists on plasma lipoprotein concentrations have been reported. Evidence from diverse lines of research has been brought together that suggests three potential mechanisms by which these antihypertensive agents affect lipoprotein metabolism. First, the known alterations in plasma triglyceride levels caused by adrenergic antagonists may be mediated through the activity of lipoprotein lipase. This enzyme, located on the capillary endothelium of adipose tissue and skeletal muscle, catabolizes chylomicrons and very-low-density lipoproteins. Catecholamine-induced changes in precapillary sphincter tone could affect the delivery of triglyceride-rich lipoproteins to endothelial lipase, cause changes in capillary endothelial surface area for lipase-binding sites, and/or modulate the synthesis of lipoprotein lipase by adipocytes and myocytes. Since high-density lipoprotein levels increase by taking up components of chylomicrons released by lipoprotein lipase, these pathways might explain the adrenergic-induced changes in high-density lipoprotein that are reciprocal to those in plasma triglycerides. Second, hepatic production of very-low-density lipoproteins might be affected by adrenergic-induced changes in insulin release. Decreased insulin release may direct glucose metabolites from adipocytes to hepatocytes for lipogenesis. Catecholamines and other glucoregulatory hormones are known to alter hepatic cholesterol synthesis and secretion of very-low-density lipoproteins. These observations also suggest that dietary carbohydrate and fat might modulate adrenergic influences on lipoprotein metabolism by other than classic means. Third, as suggested by studies of cultured fibroblasts, alpha-adrenergic antagonists may increase receptor-mediated catabolism of low-density lipoprotein.

Cimetidine increases HDL-cholesterol, particularly in the DHL 3 subfraction

Changes in high-density lipoprotein (HDL) cholesterol levels were monitored in five patients treated with cimetidine for gastrointestinal disturbances. A progressive rise of HDL cholesterolemia, statistically signficant after four weeks of treatment and highly so after eight weeks (+ 25.4%) was noted. The composition of HDL 2 varied insignificantly, whereas a marked rise of HDL 3 cholesterol (+ 23.4%) and protein (+ 13.9%) was observed at the end of eight weeks. Cimetidine seems to act in a similar way as microsomal enzyme inducers, in spite of the described inhibition of specific pathways in drug metabolism; recent evidence shows that cytochrome P-450 turnover is delayed after cimetidine. Whatever the mechanism(s), H 2 receptors may play a role in the cholesterol removal from tissues.

Effects of chronic ??-adrenergic blockade on hemodynamic and metabolic responses to endurance training

To study the influence of chronic propranolol therapy on hemodynamic and metabolic adaptations associated with endurance training, five dogs given 250 mg X d-1 propranolol therapy (P) and five control dogs (NP) were endurance trained for 7 wk using a continuously increasing treadmill workload. The P group was also evaluated pre- and post-training off the drug (P-OD) to separate drug and training effects. Training lowered mean heart rate score (HR) to a standardized multistage dog treadmill test in the NP and P-OD (P less than 0.05) and had no effect on the HR of the P group while on propranolol. At a fixed submaximal workload there were also slight reductions in cardiac output in the P group which were more pronounced (P less than 0.10) following training, and a corresponding increase in a-vDO2. Pre- and post-training metabolic studies were performed at rest, during a fixed submaximal workload, and following 30 min of recovery. During exercise, blood glucose levels were significantly lower in the P group both before and after training. While NP showed no significant change in high-density lipoprotein bound cholesterol after training, the P-OD group demonstrated a significant fall in high-density lipoprotein bound cholesterol after training (P less than 0.05). These data indicate that endurance exercise training done in the presence of chronic beta-adrenergic blockade produces training-induced hemodynamic adaptations to exercise, but beta-blockade inhibits the changes in serum lipids and lipoprotein fractions normally seen in response to an exercise conditioning program.

Mechanisms of action of absorbable hypolipidemic drugs.

Absorbable hypolipidemic agents, mostly of the aryloxyacetic acid type, are still used most widely in the general clinical treatment of hyperlipidemia. These compounds will be, therefore, the major object of this presentation. Current hypotheses on the mode of action of these drugs will be analyzed in detail and, moreover, specific problems pertaining to their use will be discussed; among these peroxisomal proliferation, reporting new findings suggestive of specific structural features most and least likely to induce this effect. Finally, aiming to the specific interest of pharmacologists working in this area, the scope and validity of new experimental methodologies, e.g., activation of lipoprotein receptors and changes in high density lipoprotein (HDL) levels, will be examined.KeywordsHigh Density LipoproteinSpecific Structural FeatureHYPOLIPIDEMIC DrugIncrease High Density Lipoprotein CholesterolIncrease High Density Lipoprotein Cholesterol LevelThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Changes in lipoprotein metabolism during a supplemented fast and an ensuing vegetarian diet period.

The effect on lipoprotein metabolism of a 2-week modified fast and an immediately ensuing 3-week period on a vegetarian diet was studied under metabolic ward conditions in 21 non-obese female and 6 male patients. The very low calorie diet induced reductions of the cholesterol concentration in all serum lipoprotein classes. In the female patients, who were all normolipoproteinaemic, the triglycerides in serum showed a slight increase during the fast, reflecting small changes in very low (VLDL) and low density lipoprotein triglycerides. This may probably be explained partly by simultaneous significant reductions of both the adipose tissue and skeletal muscle tissue lipoprotein lipase activities (LPLA). In contrast, in the male patients who had a higher VLDL level at admission, the VLDL triglycerides decreased without significant changes of high density lipoprotein (HDL) cholesterol and of LPLA in muscle. The female patients, whose weights were stable during the vegetarian diet, ended up with a lower HDL cholesterol than at the start of the trial. This effect was probably partly due to the high content of polyunsaturated fatty acids in the vegetarian diet. It is concluded that the changes of lipoprotein metabolism during supplemented fasting are quantitatively and qualitatively different in several respects in females and males.

Density gradient characterization of the high density lipoproteins in cholesterol-fed hyper- and hyporesponding patas monkeys (Erythrocebus patas).

Diet-induced changes in high density lipoprotein (HDL) density and size were studied in patas monkeys. When the animals were switched from a moderate fat-low cholesterol diet to a high fat-high cholesterol (HFHC) diet, the plasma apoA-I levels increased initially in all of the animals. The apoA-I levels remained elevated in monkeys able to maintain their plasma cholesterol concentrations near basal levels (hyporesponders), but began to decrease in monkeys who became severely hypercholesterolemic (hyperresponders), reaching levels as low as 65-70% of their basal value by 24 weeks. The larger, lipid-rich HDL (HDL2) was shown by density gradient ultracentrifugation and gradient-PAGE (polyacrylamide gel electrophoresis) to be the HDL fraction responsible for these changes in apoA-I, completely accounting for the increase in apoA-I in hyporesponders and the decrease in apoA-I in hyperresponders. The HDL3 levels remained unchanged in hyporesponders but increased markedly in hyperresponders, partially compensating for the decrease of HDL2 in those animals. Gradient-PAGE showed the HDL3 to be heterogeneous, containing at least two populations of particles of the same density but differing significantly in size. The smaller of these HDL3 were most prominent in the HFHC-fed hyperresponders. These data show that nonhuman primate HDL is both physically and metabolically heterogeneous, and indicate that a high fat-high cholesterol diet-induced hypercholesterolemia severely depresses the HDL2 levels.

Effect of weight loss in moderate obesity on plasma lipoprotein and apolipoprotein levels and on high density lipoprotein composition.

Plasma lipids, lipoprotein and apolipoprotein levels were determined in seven women and seven men with moderate obesity before, during 7 weeks of continuous weight loss (10.4% to 9.6% of body weight, 1000 kCal/day diet), and after 3 months at a stable, reduced weight. Plasma triglyceride levels decreased by 30.4% in men and by 39.4% in women (p less than 0.0001) after 1 week of caloric restriction and remained at this level throughout the study period. The plasma cholesterol decreased by 19.0% in men (p less than 0.001) and by 10.9% in women (p less than 0.01) in the period of active weight loss, but returned to prediet values after stabilization at a leaner body mass. Similar changes were observed in LDL cholesterol levels. No change in high density lipoprotein (HDL) cholesterol levels occurred during active weight reduction, but after 3 months at a reduced weight, a significant increase in HDL cholesterol was evident, and the ratio of HDL cholesterol to plasma cholesterol increased over prediet values (p less than 0.001), women). Separation of HDL subpopulations by zonal ultracentrifugation before and after weight reduction revealed that HDL2 increased slightly in men and decreased slightly in women. In both genders, HDL3 tended to decrease after weight reduction. Plasma levels of apolipoprotein A-I decreased during active weight loss, but this was significant only in women (p less than 0.05). After 3 months of reduced weight, plasma apo A-I increased to prediet levels. No significant changes in plasma apo A-II or apo E were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in lipoproteins and subfractions following oophorectomy and oestrogen replacement in peri-menopausal women

Serum cholesterol concentrations in lipoprotein fractions and subfractions were determined in 11 peri-menopausal women both before and after bilateral oophorectomy, as well as 60 days after commencement of oral oestradiol replacement therapy. Pre-operatively, all subjects were found to have normal lipid and lipoprotein concentrations. There was a post-operative increase in the total cholesterol level, which was attributed to a raised very-low-density lipoprotein (VLDL) cholesterol. Changes in high-density lipoprotein (HDL) subfractions HDL-2 and HDL-3 were noted but since these were compensatory little difference in total HDL cholesterol was observed. Following oral oestrogen replacement, the cholesterol level decreased as a result of a drop in both VLDL and low-density lipoprotein (LDL) cholesterol. The oestradiol-induced HDL cholesterol increment reflected an increase in the levels of both HDL subfractions.

Changes in high density lipoproteins in patients with hepatobiliary diseases

Lipids of HDL (high density lipoproteins) and their subfractions (HDL2 and HDL3), and LCAT activity (lecithin: cholesterol acyltransferase) were determined in hepatobiliary diseases without severe hyperbilirubinemia (less than 10 mg/dl). The decrease in major lipid constituents (cholesterol and phospholipids) of HDL was mainly attributable to the decrease in those of HDL3, except in some liver diseases of acute or severe stage (acute hepatitis in an acute stage and hepatoma) which were accompanied with a simultaneous moderate decrease in those of HDL2 and in fatty liver which showed a preferential decrease in those of HDL2. The LCAT activity also decreased in several diseases. Some of the hepatobiliary diseases, on the contrary, showed an increase in HDL-triglycerides (mostly in HDL3 and in some diseases also in HDL2) which might participate to some extent in secondary hyperlipidemia in the liver parenchymal diseases, although they were the minor lipid constituents of HDL. From results that HDL3- but not HDL2-cholesterol levels significantly correlated with serum total protein, albumin and choline esterase, it was suggested that the decrease in large constituents of HDL, particularly of HDL3, is caused by hepatocellular dysfunction which causes inhibition of protein and lipid syntheses in the liver in most of the hepatobiliary diseases except for fatty liver which has a preferential decrease in HDL2 lipids.

Lipoprotein metabolism during acute inhibition of hepatic triglyceride lipase in the cynomolgus monkey.

The role of the enzyme hepatic triglyceride lipase was investigated in a primate model, the cynomolgus monkey. Antisera produced against human postheparin hepatic lipase fully inhibited cynomolgus monkey posttheparin plasma hepatic triglyceride lipase activity. Lipoprotein lipase activity was not inhibited by this antisera. Hepatic triglyceride lipase activity in liver biopsies was decreased by 65-90% after intravenous infusion of this antisera into the cynomolgus monkey. After a 3-h infusion of the antisera, analytic ultracentrifugation revealed an increase in mass of very low density lipoproteins (S(f) 20-400). Very low density lipoprotein triglyceride isolated by isopycnic ultracentrifugation increased by 60-300%. Analytic ultracentrifugation revealed an increase in mass of lipoproteins with flotation greater than S(f) 9 (n = 4). The total mass of intermediate density lipoproteins (S(f) 12-20) approximately doubled during the 3 h of in vivo enzyme inhibition. While more rapidly floating low density lipoproteins (S(f) 9-12) increased, the total mass of low density lipoproteins decreased after infusion of the antibodies. The changes in high density lipoproteins did not differ from those in control experiments. In order to determine whether the increases of plasma concentrations of very low density lipoproteins were due to an increase in the rate of synthesis or a decrease in the rate of clearance of these particles, the metabolism of radiolabeled homologous very low density lipoproteins was studied during intravenous infusion of immunoglobulin G prepared from the antisera against hepatic triglyceride lipase (n = 3) or preimmune goat sera (n = 3). Studies performed in the same animals during saline infusion were used as controls for each immunoglobulin infusion. There was a twofold increase in the apparent half-life of the very low density lipoprotein apolipoprotein-B tracer in animals receiving the antibody, consistent with a decreased catabolism of very low density lipoproteins. Concomitantly, the rise in low density lipoprotein apoprotein-B specific activity was markedly delayed. None of these changes were observed during infusion of preimmune immunoglobulin G.Hepatic triglyceride lipase participates with lipoprotein lipase in the hydrolysis of the lipid in very low density lipoproteins, intermediate density lipoproteins, and the larger low density lipoproteins (S(f) 9-12). Thus, hepatic triglyceride lipase appears to function in a parallel role with lipoprotein lipase in the conversion of very low density and intermediate density lipoproteins to low density lipoproteins (S(f) 0-9).

Exogenous estrogens attenuate dietary hypercholesterolemia and atherosclerosis in the rabbit

The effect of exogenous estrogens upon the response to dietary cholesterol was tested in New Zealand White rabbits. Cholesterol-fed, untreated rabbits had a 10-fold increase in plasma cholesterol in 12 wk. The major increase of cholesterol occurred in very low density lipoproteins (VLDL, 43.5-fold) followed by intermediate density lipoproteins (IDL, 26-fold) and low density lipoproteins (LDL, 6-fold) with no change in high density lipoproteins (HDL). These diet induced changes were markedly attenuated in the estrogen treated animals, in whom plasma cholesterol increased only 5-fold. This increase was distributed among LDL (6-fold), IDL (7.5-fold), and VLDL (9-fold), similarly with no change in HDL. All the lipoproteins in both groups of animals were considerably enriched in cholesterol during cholesterol feeding as indicated by a high cholesterol/protein and cholesterol/triglyceride ratio. However, these ratios were lower in estrogen treated animals. There were no differences in the feed consumption, body weight or cholesterol absorption between the two groups of animals. Rabbits fed a cholesterol-rich diet but not treated with estrogen had well developed lesions in all parts of the aorta with higher content of cholesterol and phospholipids as compared to those injected with estrogen, whose aortas were completely clear of visible atherosclerosis. Equivalent total hypercholesterolemia was induced in other estrogen-treated rabbits by feeding twice the cholesterol dietary content (0.2%) as in nonestrogen-treated animals. Aortic atherosclerosis was far more evident in the latter, which had higher proportions of cholesterol-rich lipoproteins of d < 1.006 g/ml.

Serum Lipoprotein Levels During Chlorthalidone Therapy

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

CHANGES IN PLASMA LIPIDS AND LIPOPROTEINS AFTER A MODIFIED FAT DIET

20 male and female patients with type II hyperlipoproteinæmia and 10 normal male and female subjects were fed for 11-15 days a eucaloric diet containing less than 300 mg cholesterol with a polyunsaturated to saturated fatty-acid ratio of about 2·0. Male subjects and patients and female patients showed statistically significant decreases in plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels; the change in LDL-cholesterol was not significant in female subjects. The changes in lipid and lipoprotein levels in patients were greater than those in subjects, (except for the changes in high-density lipoprotein (HDL) in women, which were similar), which suggested that the magnitude of change depended on initial levels. This difference was not present when the data were evaluated as percent change. Mean levels of HDL-cholesterol decreased in both patients and subjects. However, the proportion of total cholesterol contributed by HDL and LDL, and hence the HDL/LDL ratio, was unchanged from pre-diet levels.