Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk

Low-density lipoprotein (LDL) cholesterol concentrations are most commonly estimated by the formula LDL cholesterol = total cholesterol - [triglycerides (TG)/5 + high-density lipoprotein cholesterol], although alternative factors such as TG/6 have also been used. Using standardized, automated, enzymatic lipid assays, we analyzed 4797 plasma samples from normal and dyslipidemic adults, to compare LDL cholesterol concentrations obtained after ultracentrifugation with those calculated by several such methods (i.e., TG/4-TG/8). or TG concentrations less than or equal to 0.50 g/L, TG/4 agreed best with the direct assay; for TG of 0.51-2.00 g/L, TG/4.5 was best; and for TG of 2.01-4.00 g/L, TG/5 was best. Differences in estimated values were generally small, however. At TG greater than 4.00 g/L, none of the factors tested allowed a reliable estimate of LDL cholesterol. When TG were less than or equal to 4.00 g/L, 86% of estimated LDL cholesterol values were properly classified according to National Cholesterol Education Program cutpoints when the factor TG/5 was used. We conclude that a convenient direct method for measuring LDL cholesterol is needed but, until one is available, use of the factor TG/5 will assure that most individuals with TG less than or equal to 4.00 g/L, as measured in a standardized laboratory, can be reasonably well classified for risk of coronary artery disease.     

Effect of ileal exclusion on kinetics of very low density lipoprotein triglycerides in familial hypercholesterolemia

Plasma lipoproteins, VLDL triglyceride kinetics, and bile acid and cholesterol synthesis were measured in 21 patients heterozygous for familial hypercholesterolemia with (n = 11) or without (n = 10) ileal bypass. LDL cholesterol and apoprotein B concentrations were lower, and cholesterol and bile acid synthesis, the VLDL triglyceride/cholesterol ratio, and the HDL cholesterol concentration were higher in the operated than the control patients. The VLDL triglyceride production rate was increased in the operated normotriglyceridemic patients by about 65%, whereas the fractional catabolism of VLDL triglycerides and the calculated VLDL cholesterol transport were similar in the operated and control groups. VLDL triglyceride production was not correlated with cholesterol or bile acid synthesis. The VLDL triglyceride concentration was positively correlated with the production and negatively with the fractional catabolism of VLDL triglycerides. In unoperated normotriglyceridemic patients the VLDL triglyceride production was positively correlated with LDL cholesterol (r = 0.69, p less than 0.05), LDL triglyceride (r = 0.84, p less than 0.01) and LDL apoprotein B (r = 0.80, p less than 0.01) concentrations, and with the LDL triglyceride/apoprotein B (r = 0.72, p less than 0.05) and LDL triglyceride/cholesterol (r = 0.68, p less than 0.05) ratios. None of these correlations was significant in the operated patients. We conclude that in heterozygous familial hypercholesterolemia VLDL triglyceride level depends on both VLDL triglyceride synthesis and catabolism, LDL level is proportionate to VLDL triglyceride production in the unoperated patients but not in the patients with ileal bypass, ileal exclusion results in an increase in the production rate of VLDL triglycerides in normotriglyceridemic patients but otherwise VLDL triglyceride production is poorly associated with cholesterol and bile acid synthesis, ileal exclusion may induce hepatic secretion of triglyceride-rich VLDL.     

Para-aminosalicylic acid as a lipid-lowering agent.

The capacity of para-aminosalicylic acid (PAS) to lower initially high serum lipoprotein lipid concentrations was tested in a double-blind crossover study. Thirty patients who were on a lipid-lowering diet were treated with PAS (6 gm daily) for 4 wk. There was an average reduction of the serum triglyceride concentration of 28% (p less than 0.001) and of 12% of the serum cholesterol concentration (p less than 0.001) corresponding to a reduction of very low density lipoprotein (VLDL) triglycerides of 40% (p less than 0.001) and low density lipoprotein (LDL) cholesterol of 6% (p less than 0.05). In hypercholesterolemic patients, the LDL cholesterol reduction was 14% (p less than 0.001). In patients with hypertriglyceridemia type IV, the mean reduction of the VLDL triglyceride concentration was 47% (p less than 0.01), corresponding to a serum triglyceride reduction by 37% (p less than 0.01). In spite of the decrease of VLDL concentration, there was an unexpected reduction of the lipoprotein lipase activity in adipose tissue of 16% (p less than 0.02). The glucose tolerance and the serum insulin concentrations at fasting and after glucose injection were not changed.     

Multiple Changes in Apoprotein B Containing Lipoproteins after Ethanol Withdrawal in Alcoholic Men

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol: triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospho-lipid: cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol: triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.     

Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.     

Influence of intermediate-density lipoproteins on the accuracy of the Friedewald formula

Values of low-density lipoprotein (LDL) cholesterol (C) according to the Friedewald formula (Clin Chem 1972;18:499-502) were compared with those obtained by lipoprotein fractionation in 98 healthy subjects (control group), 135 specimens from patients with peripheral vascular and cerebrovascular disease (atherosclerotic group), and 45 with chronic renal failure on hemodialysis (CRF group). All had concentrations of total cholesterol between 3.23 and 7.76 mmol/L (1.25-3.00 g/L) and triglycerides less than 3.39 mmol/L (less than 3.00 g/L). The percentage error of calculated LDL-C was 4% in controls with a cholesterol/triglycerides (C/TG) ratio for very-low-density lipoprotein (VLDL) of 0.20, but greater than 60% in those with a (C/TG)VLDL ratio of 0.40. The percentage of error in sera of patients with atherosclerosis and chronic renal failure was higher than in controls with a similar mean (C/TG)VLDL ratio. The percentage of error of calculated LDL-C increases progressively with the increase in the C/TG intermediate-density lipoprotein (IDL) ratio, both in controls and in the atherosclerotic and CRF groups. Similar findings are observed when the mean percentage of error of measured LDL-C is evaluated. The percentage of error from calculated LDL-C in the atherosclerotic and CRF groups is significantly lower than that obtained by comparison of LDL-C separated by ultracentrifugation when the "broad cut" LDL (IDL plus LDL, both by ultracentrifugation) was used. The high percentage of errors found in the groups of patients studied underlines the need for caution when assessing the reliability of the Friedewald formula, particularly in cases in which disturbances in IDL composition are suspected.     

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.     

Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.     

Conversion of type III hyperlipoproteinaemia to type IV hyperlipoproteinaemia by a fat-free, carbohydrate rich diet.

Hyperlipoproteinaemia type III has been considered a clear cut clinical entity characterized by the presence of cholesterol rich "floating" beta very low density lipoproteins (VLDL) after ultracentrifugation. Carbohydrate inducibility is pronounced in type III. This study was undertaken to elucidate the effect of a high carbohydrate diet in type III as an effort to clarify a suggested association between type III and IV hyperlipoproteinaemia. On an isocaloric fat free carbohydrate rich diet the lipoprotein pattern changed as the VLDL triglycerides increased 31 per cent on average and LDL and HDL cholesterol decreased by 40 and 22 per cent. The high ratio cholesterol/triglycerides in VLDL was normalized. The lipoprotein levels in serum after carbohydrate induction showed all characteristics of a type IV with high VLDL triglycerides, normal cholesterol/triglyceride ratio in VLDL, subnormal cholesterol levels in LDL and HDL with changed relation between LDL1 and LDL2. On electrophoresis the floating beta band disappeared. It is probable that depending on the nutritional situation, the metabolic defect in type III may be expressed either as a type III or a type IV. An explanation of the effects of the carbohydrate rich diet on the lipoprotein pattern is suggested.     

Postprandial lipemic response and lipoprotein composition in subjects with low or high cholesterol absorption efficiency

BACKGROUND: The purpose of this study was to investigate the effect of differences in cholesterol absorption efficiency on the postprandial lipemia and lipoprotein composition. METHODS: Fifteen healthy subjects were divided into low and high cholesterol absorbers on the basis of serum cholestanol to cholesterol ratio. A high-performance liquid chromatographic method with evaporative light scattering detection was developed for quantitation of free and esterified cholesterol, triglycerides and major phospholipids from the same lipid extract in two runs utilizing the same internal standard. RESULTS: The free cholesterol to phosphatidylcholine ratio of chylomicrons was higher in the high cholesterol absorption group. The total increase of cholesterol in combined chylomicron and very low density lipoprotein (VLDL) fraction was also higher in this group. Chylomicron free cholesterol and cholesterol ester responses correlated with fasting low density lipoprotein (LDL) cholesterol. VLDL and VLDL1 triglyceride responses correlated inversely with fasting insulin and homeostasis model assessment of insulin resistance. CONCLUSIONS: High cholesterol absorption efficiency was seen in chylomicrons as higher cholesterol to phosphatidylcholine ratio during the postprandial peak. Chylomicron cholesterol response was linked to fasting LDL cholesterol and low VLDL triglyceride response to fasting insulin.     

Concentration and composition of the lipoprotein classes in human umbilical cord serum.

The concentration and composition of the lipoprotein density classes d less than 1.006 (VLDL), d = 1.006 - 1.064 (LDL), and d = 1.064 - 1.21 (HDL) of human umbilical cord serum were investigated by means of preparative ultracentrifugation. The concentrations of all the density classes, in particular that of the VLDL, are lower than in adults; the values correspond to 8.1 (VLDL), 59.2 (LDL), and 77.4 (HDL) mg/100 ml. About 15% of the total cholesterol and roughly 40% of the total lipid phosphorus did not float at the highest density of 1.21. The composition of the LDL and the HDL was principally in agreement with the pattern obtained in adults. The VLDL of the cord serum, however, showed a lower amount of triglycerides (45%) and a higher content of proteins (22%) than the VLDL from serum of adults. In cord serum only 25% of the total triglycerides are associated with the VLDL fraction, while more than 50% of the triglycerides circulate as a constituent of the LDL.     

Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia

The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post-heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates.     

Quantitative analysis of lipoproteins in hyperlipoproteinemias of type IIa, IIb and IV (author's transl)]

Cholesterol and triglyceride content of serum lipoprotein fractions isolated by ultracentrifugation have been studied in 33 healthy subjects and in 56 subjects affected by hyperlipoproteinemia of type IIa, IIb and IV. Patients with atherosclerotic disease were characterized by a general decrease of HDL cholesterol and by a negative correlation between HDL cholesterol and VLDL triglycerides; patients with type IIb and IV showed an increase of LDL lipoproteins. The increase of triglycerides in type IIb and IV was caused by elevation of VLDL triglycerides or LDL triglycerides, and the increase of cholesterol in type IIb is sometimes caused by elevation of VLDL cholesterol. It is evident that several subtypes exist within Fredrickson's classification. Patients with cerebral arterial disease when compared with patients affected by non-ischaemic disease, showed a negative and significant correlation between HDL cholesterol and total cholesterol.     

Response of plasma lipoproteins and acute phase proteins to myocardial infarction.

Plasma concentrations of lipoprotein-lipids, apolipoprotein B (apoB) and of seven other proteins have been estimated serially in 27 patients up to three months following myocardial infarction. Results were compared with those from age- and sex-matched control subjects. At three months the mean total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol concentrations were higher than those of the control subjects, whereas very low density lipoprotein (VLDL) cholesterol, total and VLDL triglyceride, and total and LDL apolipoprotein B concentrations were not significantly different. Relative to concentrations at three months total and LDL cholesterol and apolipoprotein B concentrations fell markedly, and a slight fall occurred in HDL cholesterol following infarction. VLDL cholesterol and total and VLDL triglyceride were decreased only on day one. Albumin and transferrin concentrations were higher and alpha 1-acid glycoprotein was lower at three months than in the control subjects; alpha 2-macroglobulin, caeruloplasmin, haptoglobin and immunoglobulin IgM were not significantly different. Following infarction albumin and transferrin fell, alpha 2-macroglobulin did not change, and alpha 1-acid glycoprotein, caeruloplasmin, haptoglobin and IgM rose. The changes in both lipids and protein are probably part of the general metabolic response to trauma.     

Increase in plasma total and lipoprotein cholesterol during incubation of whole blood samples at 37 degrees C--influence of LCAT inhibitors.

Incubation of whole blood samples at 37 degrees C caused a time-dependent increase in plasma cholesterol concentrations. In samples from 40 fasting healthy males, plasma cholesterol rose by 13.6 +/- 3% during 24 h (P less than 0.001). Changes in cholesterol concentrations were found in both the HDL fraction and the VLDL/LDL fraction. The increase in lipoprotein cholesterol concentrations correlated positively with the initial levels of HDL cholesterol and apo A-I; and with the original levels of VLDL/LDL cholesterol, apo B and triglycerides. The increase in plasma total cholesterol was not related to the HDL cholesterol and apo A-I concentrations. It was more pronounced in samples with elevated plasma concentrations of total cholesterol, VLDL/LDL cholesterol, apo B and triglycerides. The elevation in plasma total cholesterol resulted from an increase in cholesteryl esters, whereas free cholesterol decreased. After LCAT inhibition no changes in total, free and esterified cholesterol were observed. Therefore, increase in plasma cholesterol seems to represent a LCAT-dependent cholesterol transport out of blood cells.     

Regulation of the production and catabolism of plasma low density lipoproteins in hypertriglyceridemic subjects. Effect of weight loss.

In subjects with hypertriglyceridemia, plasma concentrations of low density lipoprotein (LDL) cholesterol are often normal or reduced. Perturbations that alter plasma very low density lipoprotein (VLDL) concentrations are associated with opposite changes in plasma LDL levels. To determine the mechanisms regulating plasma LDL levels, we used 131I-VLDL and 125I-LDL to measure the fractional catabolic rates (FCR), production rates (PR), and rates of interconversion of apoprotein B (apo B) in VLDL, intermediate density lipoprotein, and LDL in six hypertriglyceridemic subjects pre- and post-weight reduction. [2-3H]glycerol was used to quantitate VLDL triglyceride PR. All data are presented as mean +/- SD. Percent ideal body weight fell from 132 +/- 17.9 to 119 +/- 15.9% in the group, P less than 0.05. After weight loss, plasma VLDL triglyceride (486.0 +/- 364.1 vs. 191.3 +/- 65.4 mg/dl, P less than 0.05) and VLDL apo B (32.2 +/- 12.0 vs. 14.8 +/- 6.8 mg/dl, P less than 0.05) concentrations were reduced. VLDL triglyceride PR also fell after weight reduction (56.6 +/- 39.0 vs. 28.6 +/- 23.1 mg/kg per h, P less than 0.05), as did VLDL apo B PR (47.9 +/- 41.4 vs. 19.0 +/- 14.1 mg/kg per d, P less than 0.05). Pre-weight loss, plasma LDL cholesterol and apo B levels were low-normal or reduced (64.0 +/- 12.6 and 58.4 +/- 11.9 mg/dl, respectively) despite normal or elevated LDL apo B PR (17.4 +/- 7.2 mg/kg per d). The reduced cholesterol and apo B levels were associated with increased FCRs (0.68 +/- 0.29 d-1) and reduced cholesterol/protein ratios (1.01 +/- 0.18) in LDL. The plasma levels of LDL cholesterol and apo B rose after weight reduction (84.8 +/- 24.9, P less than 0.05; and 69.5 +/- 14.3 mg/dl, P less than 0.05, respectively, vs. base line). These increased concentrations resulted from a combination of events. First, the FCR for LDL apo B fell in five of six subjects with a significant reduction for the group as a whole (0.48 +/- 0.11 d-1, P less than 0.05 vs. base line). Second, the cholesterol/protein ratio increased in all six subjects with a significantly greater mean after weight loss (1.25 +/- 0.27, P less than 0.05 vs. base line). In contrast, the LDL apo B PR fell or was essentially unchanged in the six subjects after weight loss (mean, 14.4 +/- 2.8 mg/kg per d; NS vs. pre-weight loss). The changes in LDL catabolism and composition were associated with changes in the source of LDL apo B. Pre-weight loss, 73.3% of LDL was derived from VLDL, while 26.7% was directly secreted into plasma. Post-weight reduction, VLDL-derived LDL fell to 46.8% of total, while direct secretion accounted for 53.2% of LDL production. These changes were significant; P < 0.95. Thus, all subjects had direct secretion of LDL apo B and the magnitude of this source of VLDL triglyceride secretion. These results indicate that the regulation of plasma LDL levels in hypertriglyceridemic subjects is quite complex and that the rise in LDL levels after weight loss results from reduction in the fractional catabolism of this lipoprotein. The fall in the FCR is associated with changes in the source of LDL and in its composition.     

Conversion of Type III Hyperlipoproteinaemia to Type IV Hyperlipoproteinaemia by a Fat-Free, Carbohydrate Rich Diet

Abstract. Hyperlipoproteinaemia type III has been considered a clear cut clinical entity characterized by the presence of cholesterol rich "floating" beta very low density lipoproteins (VLDL) after ultracentri-fugation. Carbohydrate inducibility is pronounced in type III. This study was undertaken to elucidate the effect of a high carbohydrate diet in type III as an effort to clarify a suggested association between type III and IV hyperlipoproteinaemia. On an isocaloric fat free carbohydrate rich diet the lipoprotein pattern changed as the VLDL triglycerides increased 31 per cent on average and LDL and HDL cholesterol decreased by 40 and 22 per cent. The high ratio cholesterol/triglycerides in VLDL was normalized. The lipoprotein levels in serum after carbohydrate induction showed all characteristics of a type IV with high VLDL triglycerides, normal cholesterol/triglyceride ratio in VLDL, subnormal cholesterol levels in LDL and HDL with changed relation between LDL₁ and LDL₂. On electrophoresis the floating beta band disappeared. It is probable that depending on the nutritional situation, the metabolic defect in type III may be expressed either as a type III or a type IV. An explanation of the effects of the carbohydrate rich diet on the lipoprotein pattern is suggested.     

High protein diet complements resin therapy of familial hypercholesterolemia.

The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia.     

Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man.

Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal.     

Fish eye disease: a new familial condition with massive corneal opacities and dyslipoproteinaemia Clinical and laboratory studies in two afflicted families

Abstract. Fish eye disease (FED) is characterized by severe corneal opacities, causing impaired vision, and dyslipoproteinaemia: hypertriglyceridaemia, raised levels of very low density lipoproteins (VLDL), triglyceride enrichment of low density liproteins (LDL) and reduction of high density lipoproteins (HDL). The disease is described in two unrelated families. In both there was a high proportion of low HDL in relatives without eye disease.
VLDL, LDL and HDL had normal electrophoretic mobilities. The concentrations of VLDL cholesterol and triglycerides were increased fivefold. LDL cholesterol levels were normal but LDL triglycerides markedly increased. HDL cholesterol was reduced by 90% as were the levels of HDL apolipoproteins. The major part of HDL cholesterol was in the HDL₃ fraction. FED HDL were smaller than normal with molecular weights of 115,000 daltons.
Lecithin: cholesterol acyltransferase activity and amount of cholesterol esters in serum were normal. Postheparin lipoprotein and hepatic lipases showed normal or subnormal values.
Clinically FED differs from other familial conditions with deficiency of HDL such as Tangier disease, LCAT-deficiency and Milano-AI-apoprotein disease. In spite of the extremely low HDL cholesterol FED is not characterized by premature atherosclerosis. Mechanisms for the dyslipoproteinaemia are discussed.