Plasma Lipoprotein Cholesterol Concentrations Research Articles

Effect of Gemfibrozil Treatment in Sulfonylurea-Treated Patients with Noninsulin-Dependent Diabetes Mellitus*

This study was initiated to 1) assess gemfibrozil's ability to lower plasma triglyceride (TG) concentration in patients with NIDDM, and 2) determine whether this effect was associated with any changes in glycemic control. Measurements were made of mean hourly plasma glucose, insulin, TG, and FFA concentrations from 1200-1600 h in response to a test meal; hepatic glucose production (HGP); insulin-stimulated glucose uptake during a hyperinsulinemic glucose clamp study (MCR); and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment. Although ambient plasma TG and FFA concentrations fell significantly, plasma glucose, insulin, HGP, concentrations fell significantly, plasma glucose, insulin, HGP, and glucose MCR did not change. However, when patients were divided into two groups, those with fasting plasma glucose levels above 9 mmol/L (fair control) and those with levels below 9 mmol/L (good control), a different phenomenon was observed. Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose (15.1 +/- 1.7 to 12.6 +/- 0.9 mmol/L; P less than 0.001), insulin (523 +/- 59 to 471 +/- 75 pmol/L; P less than 0.001), FFA (652 +/- 150 to 504 +/- 76 mumol/L), and HGP (9.5 0.4 to 8.1 +/- 0.4 mumol/kg.min; P less than 0.005), and an increase in glucose MCR (2.63 +/- 0.49 to 3.72 +/- 0.54 mL/kg.min; P less than 0.07) in association with a fall in TG from 6.9 +/- 1.3 to 3.5 +/- 0.9 mmol/L (P less than 0.001). Although fasting low density lipoprotein cholesterol increased (1.8 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.05), the ratio of total to high density lipoprotein cholesterol decreased (6.84 +/- 0.88 to 5.80 +/- 1.05; P less than 0.02). Despite a significant fall in mean hourly TG concentration (4.6 +/- 0.7 to 3.8 +/- 0.7 mmol/L; P less than 0.001), neither insulin, FFA, HGP, nor glucose MCR changed in patients in good control. Furthermore, the mean hourly plasma glucose concentration increased from 9.2 +/- 0.7 to 11.7 +/- 1.4 mmol/L (P less than 0.001). Low density lipoprotein cholesterol also increased in this group (1.9 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.02), but, as before, the ratio of total to high density lipoprotein cholesterol decreased (8.15 +/- 1.93 to 6.36 +/- 1.03; P less than 0.02).

Dietary α-linolenic acid is as effective as oleic acid and linoleic acid in lowering blood cholesterol in normolipidemic men

The effect of dietary oleic acid (OA), linoleic acid (LA), and linolenic acid (LNA) on plasma lipid metabolism was studied in eight normolipidemic men. A mixed-fat diet composed of conventional foods was fed during 6-d pre- and post-experimental periods. The same basic diet but with 75% of the fat (26% of total energy) provided by sunflower and olive; canola; soybean; and sunflower, olive, and flax oils was fed during four 18-d experimental periods. Mean plasma total cholesterol (-18%), low-density-lipoprotein-cholesterol, (-22%) and very-low-density-lipoprotein-cholesterol (-41%) concentrations were significantly (P less than 0.004) lower after the experimental diets than after the mixed-fat diet. Mean serum apolipoprotein B (-19%) and apolipoprotein A-I (-9%) concentrations were also significantly (P less than 0.0007) lower after the experimental diets. The experimental diets were equally effective in lowering total and lipoprotein cholesterol and apolipoprotein concentrations in plasma, indicating that dietary OA, LA, and LNA were equally hypocholesterolemic.

Comparison of the Effects of Atenolol and Nifedipine on Glucose, Insulin, and Lipid Metabolism in Patients With Hypertension

Various aspects of carbohydrate and lipid metabolism have been studied in two groups of patients with mild hypertension before and after four months of treatment with either nifedipine (n = 12) or atenolol (n = 12). Mean (+/- SEM) blood pressure fell to the same degree following treatment with either nifedipine (147 +/- 3/98 +/- 2 to 134 +/- 2/85 +/- 2 mm Hg) or atenolol (149 +/- 3/99 +/- 2 to 135 +/- 2/86 +/- 3 mm Hg). Circulating plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8:00 AM to 4:00 PM, before and after breakfast (8:00 AM), and at lunch time (noon). The response to treatment was different in the two groups. Specifically, plasma glucose concentration were unchanged and insulin concentrations were higher in association with atenolol treatment. In contrast, nifedipine-treated patients had similar plasma insulin, but lower plasma glucose and triglyceride concentrations after four months of therapy. The changes in day-long plasma glucose and insulin responses suggested that resistance to insulin-stimulated glucose uptake had increased in association with atenolol treatment and decreased following nifedipine. This conclusion was supported in that measurement of insulin-stimulated glucose disposal showed a decrease in atenolol-treated patients and an increase in nifedipine-treated patients. Finally, plasma lipoprotein cholesterol concentrations did not change following atenolol therapy, whereas plasma high density lipoprotein cholesterol increased in association with nifedipine administration. These data show that changes in carbohydrate and lipid metabolism observed with treatment of mild hypertension can vary significantly as a function of the drug used, despite similar beneficial effects on blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of estrogen and progesterone on plasma lipoproteins and experimental atherosclerosis in the baboon (Papio sp.).

We determined the effect of estrogen and progesterone on plasma cholesterol and lipoprotein cholesterol concentrations and on arterial lesions in 24 ovariectomized and hysterectomized baboons fed a high-cholesterol/high-saturated-fat diet. These baboons were divided into four groups: untreated control (C); estrogen, 100 micrograms/kg/week injected i.m. (E); progesterone, 3 mg/kg/day (P); and estrogen plus progesterone (E + P). The treatment regimen continued for 18 months. Cholesterol levels in plasma and lipoproteins were measured before hormone treatment and at 3, 10, and 18 months of treatment. Postheparin plasma lipoprotein lipase (LPL) activity was also measured during the treatment. After 18 months of hormone treatment, baboons were necropsied and arterial lesions were measured. Hormone treatment significantly influenced plasma cholesterol (P greater than C greater than [E + P] greater than E) and very low density lipoprotein plus low density lipoprotein (VLDL + LDL) cholesterol (P greater than C greater than [E + P] greater than E), with very little effect on high density lipoprotein (HDL) cholesterol concentration. The E + P group had a significantly higher HDL cholesterol concentration than did the P group. The (VLDL + LDL)/HDL cholesterol ratios in the E and E + P groups were significantly lower than those in the P and C groups. LPL activities were significantly lower in the E group compared with those in the E + P and P groups. Hormone treatment significantly influenced lesions in four (innominate, carotid, iliac, and abdominal aorta) of seven arteries. The P group had the most fatty streaks, and the E + P group had the least.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of four days of regular, moderate consumption of ethanol on high-density lipoprotein cholesterol concentrations in plasma

Effects of four days of regular, moderate consumption of ethanol on high-density lipoprotein cholesterol concentrations in plasma

The effects of a single dose of dilevalol on [3H]‐noradrenaline plasma kinetics and plasma lipoprotein cholesterol concentrations.

1. A single oral dose of dilevalol (200 mg or 400 mg) or placebo was administered to 15 normal male volunteers in a double-blind, random order crossover study. 2. Dilevalol had no significant effect on supine blood pressures or heart rates, but caused a significant fall in systolic blood pressure 1 and 30 min following standing, and attenuated the rise in diastolic blood pressure and heart rate that accompanies standing. 3. Dilevalol caused a dose dependent increase in plasma noradrenaline levels from arterialized blood which was due to an increase in noradrenaline spillover with no change in clearance. 4. Dilevalol increased plasma levels of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) (which is formed in sympathetic nerves following neuronal uptake of noradrenaline), indicating that the increase in noradrenaline spillover was not due to the blockade of neuronal uptake. 5. Acute dilevalol administration had no effect on total plasma cholesterol, HDL-cholesterol or LDL-cholesterol levels.

Reduced Membrane Fluidity in Platelets From Diabetic Patients

Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography

The effects of time of sampling on plasma lipids and lipoprotein cholesterol concentrations were investigated in 88 patients undergoing elective coronary angiography. Patients with a myocardial infarction or major surgery within 6 weeks before catheterization were excluded. All subjects were sampled in the fasting state at the time of arteriotomy before systemic heparinization and at least 30 days after discharge from the hospital (mean 275 days) in the free living state. No statistically significant differences were noted in total cholesterol (220 ± 51 vs 226 ± 48 mg/dl), triglycerides (191 ± 77 vs 191 ± 113 mg/dl) and calculated low-density lipoprotein cholesterol levels (149 ± 46 vs 150 ± 43 mg/ dl). High-density lipoprotein cholesterol values were significantly lower (p <0.0001) in subjects sampled before catheterization than in the free living state (32 ± 10 vs 37 ± 10 mg/dl, mean change 14%). Moreover, the frequency of high-density lipoprotein cholesterol <35 mg/dl was 77% before catheterlzation and 44% in the free living state. This effect was neither due to β-adrenergic drugs nor to the length of time between samplings. In view of these findings, a screening lipld profile for patients with coronary artery disease should be performed in the free living state.

Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain.

Concentrations of total cholesterol and cholesterol in the various lipoprotein fractions were measured in vegans, vegetarians, fish eaters (who did not eat meat), and meat eaters. Total and low density lipoprotein cholesterol concentrations were higher in meat eaters than vegans, with vegetarians and fish eaters having intermediate and similar values. High density lipoprotein cholesterol concentration was highest in the fish eaters but did not differ among the other groups. There were striking trends with age in total and low density lipoprotein cholesterol concentrations, which differed between men and women: women showed a steady increase in concentration with age, whereas concentrations in men did not increase appreciably after the age of 40, which may partly explain sex differences in the prevalence of coronary heart disease. The differences in total cholesterol concentration suggest that the incidence of coronary heart disease may be 24% lower in lifelong British vegetarians and 57% lower in lifelong vegans than in meat eaters.

Dietary protein effects on cholelithiasis in hamsters: Interaction with amino acids and bile acids

AbstractThe objective of this experiment was to study the effects of dietary cottonseed protein and casein on plasma and biliary lipids, plasma amino acids and gallstones in hamsters. Thirty‐four male hamsters (60 ± 5 g) were fed either the lithogenic “Dam Diet” (containing 20% casein, 74.3% sucrose and 5.7% vitamin‐mineral mix) or a similar diet that contained 20% cottonseed protein for 30 days. Both diets contained protein as a protein isolate. The concentration of alpha‐aminobutyric acid was significantly elevated in the casein‐fed group. Significant differences in the total plasma cholesterol or lipoprotein cholesterol concentrations were not observed between the two dietary groups.A significant elevation in the absolute concentration of biliary cholesterol was observed in the casein‐fed hamsters. Cottonseed protein‐fed animals exhibited a significantly elevated concentration of bile acids. The ratio of glycochenodeoxycholic:glycocholic acid was significantly higher in the cotton‐seed protein‐fed group. This study reports that an elevated concentration of biliary cholesterol with a concomitant decrease in bile acid concentration yields a condition favorable to gallstone formation. It is proposed that cottonseed protein may have a specific effect on the bile acid pool by increasing the ratio of glycochenodeoxycholic acid:glycocholic acid which, in turn, prevents formation of cholesterol gallstones.

Psychosocial and reproductive influences on plasma lipids, lipoproteins, and atherosclerosis in nonhuman primates

Until recently, research in experimental atherosclerosis focused primarily on nutritional influences on plasma lipids, lipoproteins, and atherosclerosis. We review here the results of recent studies of independent and interactive influences of psychosocial and reproductive influences on atherosclerosis in nonhuman primates. These studies have produced evidence that, as in human beings, individuals with certain personality characteristics who are frequently faced with stressful or challenging situations are at increased risk of coronary artery disease. Preliminary evidence suggests that this relationship may be mediated, in part, by heightened sympathetic arousal, i.e., cardiovascular hyperresponsiveness, to the environmental challenge. Also, as in human beings, evidence has been produced that certain negative behavioral and psychosocial variables can have a significant independent influence on plasma lipids. As regards reproductive influences, the cynomolgus macaque seems to share with premenopausal white women a relative protection against coronary artery atherosclerosis. This "female protection" against diet-induced atherosclerosis is abolished by ovariectomy, which also results in increased total plasma and low density lipoprotein (LDL) cholesterol concentrations. Subordinate social status also seems to abolish female protection in some individuals. Preliminary evidence suggests that subordinate females most liable to this loss of protection are those with apparent stress-induced chronic ovarian endocrine dysfunction, which, in turn, is associated with increased plasma LDL cholesterol and decreased plasma high density lipoprotein (HDL) cholesterol concentrations.

Effects of short-term aerobic conditioning and high cholesterol feeding on plasma total and lipoprotein cholesterol levels in sedentary young men

The plasma total cholesterol (TC) and lipoprotein cholesterol concentrations of sedentary young men (n = 23) were determined during 4 wk of controlled feeding and 6 wk of supervised aerobic conditioning. Subjects were assigned to dietary treatments of 400 mg cholesterol per day (M) or 1400 mg cholesterol per day (H); both diets had a P/S ratio of about 0.6. Dietary groups M and H were subdivided into exercise (MX and HX) and sedentary (MS and HS) groups. Compared to the sedentary groups, MX and HX exhibited significant (p < 0.01) improvements in cardiorespiratory fitness. After 2 and 4 wk of high cholesterol feeding, group HS exhibited significant (p < 0.05) elevations in TC (+30 ± 7 and +32 ± 9 mg/dl) with nonsignificant increases in very low-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Group HX exhibited consistent weekly increases in high-density lipoprotein cholesterol (HDL-C) (from 46 ± 3 mg/dl, the base level, to 53 ± 4 mg/dl at wk 4) with aerobic conditioning. By combining exercise and sedentary group data at each level of dietary cholesterol it was shown that TC and HDL-C levels significantly (p < 0.05) increased by the 4th wk of high cholesterol feeding. The TC/HDL-C ratio significantly (p < 0.05) increased for the sedentary subjects as compared to all the exercising subjects by wk 4 of controlled feeding.

Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol.

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.

Plasma lipid and lipoprotein cholesterol concentrations in adult males consuming normal and high cholesterol diets under controlled conditions

Twenty-three young adult males were fed diets containing either 400 or 1400 mg of cholesterol per day under controlled conditions for 4 wk. There were minimal differences between the two diets in total protein, carbohydrate, fat, and the P/S fatty acid ratio. In both diets 400 mg of cholesterol was supplied from nonegg food sources; the additional 1000 mg of cholesterol was from four whole eggs. Blood samples were collected after a 12- to 14-h fast at the beginning of the study, weekly throughout the experimental period, and 1 wk after completion of the study. Plasma total cholesterol and triglycerides and high-density, low-density, and very low-density lipoprotein cholesterol levels were measured. No significant differences in plasma total cholesterol, triglycerides, and lipoprotein cholesterol levels were observed between groups at any time. However, plasma cholesterol and cholesterol content of individual lipoproteins varied considerably among the individual subjects fed the high cholesterol diet. The importance of changes in the properties and metabolic activity of individual lipoproteins induced by dietary cholesterol with or without gross changes in the cholesterol levels remains to be determined.

Changes in plasma high density lipoproteins and lipolytic enzymes after long-term, heavy ethanol consumption

Plasma high density lipoprotein (HDL) concentrations are often increased in chronic alcoholism. The mechanism for this hyperalphalipoproteinaemia was investigated in seven male chronic alcoholics. Determinations of lipoprotein lipase, hepatic lipase and lecithin-cholesterol acyl trailsferase activities and of lipid concentrations in plasma and lipoproteins were made immediately after a debauch and during an abstinence period of 10 days. The lipoprotein patterns registered immediately after cessation of ethanol intake were characterized by elevated concentrations of HDL, especially the HDL2 subclass. Postheparin plasma lipoprotein lipase activities were also increased. During the observation period HDL levels and lipoprotein lipase activities decreased by about 40%. Concomitantly there was a small but significant increase in the concentrations of plasma and very low density lipoprotein (VLDL) triacylglycerol, and of plasma and low density lipoprotein (LDL) cholesterol concentrations. The results suggest th...

Plasma lipid concentrations and lecithin:cholesterol acyltransferase activity in normolipidemic subjects given fenofibrate and colestipol

Plasma lipids and lipoprotein cholesterol concentrations and lecithin:cholesterol acyltransferase activity were measured in 7 normolipidemic subjects before, and 7 days after, the administration of fenofibrate (300 mg daily) and colestipol (15 g daily) taken separately or simultaneously. Fenofibrate provoked a significant decrease in the mean plasma triglycerides (26%) and cholesterol (10%) concentration; only plasma cholesterol concentrations were significantly lowered by colestipol (26%). The cholesterol lowering effects of the two drugs were additive as was observed when colestipol was added to fenofibrate. The mean plasma high density lipoprotein cholesterol (HDL-C) concentration was significantly increased by fenofibrate (10%) and when colestipol was added to fenofibrate (15%), but not by colestipol alone. Both fenofibrate and colestipol caused significant reduction of the mean plasma low density lipoprotein cholesterol (LDL-C) concentration and the mean plasma LDL-C/HDL-C ratio (13% and 18%, respectively, with fenofibrate, 44% and 52% with colestipol, and 53% and 62% with colestipol added to fenofibrate). The mean plasma fractional esterification rate was significantly increased by 25% and 12%, respectively, with fenofibrate and colestipol when taken separately, and still more (91%) when colestipol was added to fenofibrate. The mean plasma molar esterification rate was significantly lowered by colestipol, but remained unchanged with the other drug regimens. This study shows that fenofibrate and colestipol given to normolipidemic subjects can induce in a very short period of time (7 days) marked changes in lipoprotein metabolism. Interpretations of the findings in relation to lipoprotein metabolism are discussed.

Moderate Exercise and High-Density Lipoprotein-Cholesterol

The effects of a 13-week moderate exercise program on fasting plasma insulin, lipids, and lipoprotein cholesterol concentrations were studied in 32 sedentary, middle-aged men with coronary artery disease. The preponderant component of the exercise program was walking or slow jogging. There was no significant change in the systolic blood pressure and pulse rate product response to a standard exercise load. The high-density lipoprotein-cholesterol (HDL-C) level increased, and the fasting plasma insulin concentration decreased. There were no significant changes in plasma triglycerides or low-density lipoprotein cholesterol levels. In sedentary subjects with coronary artery disease, a modest increase in activity can result in an increase in the HDL-C level and a decrease in the plasma insulin concentration. These changes occurred in the absence of variations in diet, smoking habits, adiposity, or plasma triglyceride concentrations and did not require a cardiovascular training effect.

A comparative trial of clofibrate and nicotinyl alcohol tartrate in hyperlipoproteinemic patients

The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p less than 0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect was not statistically significant due to the large variance. Both drugs decreased (p less than 0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p less than 0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids.

Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man

The plasma concentrations of unesterified and esterified cholesterol within very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins have been examined in relation to the metabolism and pool size of cholesterol in normal and hyperlipidaemic subjects. Cholesterol metabolism was assessed as faecal endogenous neutral and acidic steroid excretion, a 2-pool model of cholesterol turnover, and in vitro plasma cholesterol esterifying activity. VLDL total cholesterol (TC) concentration was positively correlated with cholesterol turnover, endogenous neutral steroid excretion, bile acid excretion and the absolute rate of plasma cholesterol esterification. The correlations with cholesterol turnover and neutral steroid excretion, but not that with bile acid excretion, remained significant when these were corrected for their relationships to body weight. LDL-TC was negatively correlated with the fractional rate of plasma cholesterol esterification and, in subjects with primary type IIa hyperlipoproteinaemia, also with the rate constant for cholesterol elimination from the rapidly exchanging cholesterol pool. No correlation was found between LDL-TC concentration and bile acid excretion. HDL-TC concentration was negatively correlated with both the rapidly and slowly exchanging pools of tissue cholesterol, after correction for their relationships to body weight and adiposity. In contrast, cholesterol pool sizes were not correlated with the concentration of VLDL or LDL-TC; nor was there any relationship to plasma cholesterol esterifying activity. No correlation was found between the relative proportions of unesterified and esterified cholesterol within any lipoprotein fraction and either the pool size or metabolism of cholesterol. These findings accord with previous reports of enhanced cholesterol metabolism in subjects with elevated VLDL concentrations and of impaired plasma LDL and cholesterol clearance in patients with primary type IIa hyperlipoproteinaemia. The demonstration that HDL-TC concentration is negatively correlated with body cholesterol pool size supports in vitro evidence for a role of HDL in tissue cholesterol clearance.