Effects of probucol on plasma lipids and lipoproteins in familial hypercholesterolemic patients with and without apolipoprotein E4

It has been reported that total cholesterol (Chol) response to probucol is greater in familial hypercholesterolemic (FH) patients with apo E4 than in those without apo E4. We further examined the effect of probucol on plasma triglyceride (TG) and lipoprotein-Chol levels as well as total Chol levels in heterozygous FH patients with apo E4 (n = 14 for apo E4/3, n = 1 for apo E4/4) and without apo E4 (n = 31 for apo E3/3). Probucol was administered in a dosage of 500 mg twice daily for 3 months. The reduction in total Chol levels was significantly greater in FH patients with apo E4 (-90 mg/dl, -27.5%) than in those without apo E4 (-41 mg/dl, -13.7%). The reduction in low density lipoprotein (LDL)-Chol levels was also significantly greater in FH patients with apo E4 (-73 mg/dl vs. -34 mg/dl). There was a significant difference in the change in TG and very low density lipoprotein (VLDL)-Chol levels with treatment between the FH patients with apo E4 (-37 and -8 mg/dl, respectively) and without apo E4 (+8 and +2 mg/dl, respectively). However, there was no significant difference in the reduction in HDL-Chol levels between the 2 groups (-9 mg/dl vs. -9 mg/dl). It is concluded that FH patients with apo E4 showed the greater reduction in plasma TG levels as well as total Chol levels with probucol treatment than those without apo E4, and that the greater reduction in total Chol levels in them, as reported previously, was mainly due to the greater reduction in LDL-Chol levels and slightly due to that in VLDL-Chol levels.     

Characterization of low-density lipoproteins from patients with recessive X-linked ichthyosis

We investigated lipoprotein metabolism in 14 patients with recessive X-linked ichthyosis (RXLI), a metabolic disease characterized by scaly skin, corneal opacity and steroid sulfatase deficiency. Plasma total cholesterol (TC) levels ranged from normal to slightly low (mean +/- SD: 156 +/- 28 mg/dl). Four patients showed a mild or moderate elevation of plasma triglyceride (TG) levels ranging from 150 to 365 mg/dl. The apoprotein B (apo B) to TC ratio was higher than in normal controls (0.63 +/- 0.11 vs. 0.52 +/- 0.07, P less than 0.01), while plasma apoB levels were within the normal range (99 +/- 17 mg/dl). Polyacrylamide gel electrophoretic mobility of low-density lipoprotein (LDL) was markedly increased in all patients, and further analyses showed that this finding was not due to a change in the particle size of the LDL but to an increased content of cholesterol sulfate (1.0-2.3% of the LDL-cholesterol content). In addition to the alteration of electrophoretic mobility, marked changes in the lipid and apoprotein compositions of the LDL fraction were observed; cholesterol ester content in LDL (LDL-CE) was significantly lower than that of control subjects (37 +/- 4% vs. 41 +/- 2% of total lipids, P less than 0.01), while the triglyceride content (LDL-TG) and apo B to cholesterol ratios in LDL were significantly higher than those of controls (18 +/- 7 vs. 10 +/- 2, P less than 0.001; 1.21 +/- 0.19 vs. 0.73 +/- 0.05, P less than 0.001, respectively). This anionized LDL, in which cholesterol sulfate was increased, was shown to bind to the LDL receptor of fibroblasts to much the same extent as normal LDL. In conclusion, the increase in cholesterol sulfate in LDL fraction not only alters the electrophoretic moiety but also the relative contents of apoB, cholesterol, and triglyceride in the lipoprotein. It does not change the affinity of LDL for the LDL receptor.     

Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects.

Utilising a combination of m-aminophenyl-borate affinity chromatography and an immunoradiometric assay for apolipoprotein B (apo B), we have developed a specific and highly sensitive (6 ng/ml) procedure for the assay of glycated apo B. We studied 52 diabetic patients, 50 non-diabetic control subjects and 12 patients heterozygous for familial hypercholesterolaemia (FH). Both insulin-dependent and non-insulin dependent diabetics were included in our study. Total apo B in the diabetics (108 +/- 5 mg/dl; mean +/- S.E.M) was increased (controls: 95 +/- 4 mg/dl; P less than 0.05). In the FH group the serum apo B concentration (216 +/- 24 mg/dl) was significantly higher (P less than 0.001) than both the other groups studied. Both the serum glycated apo B concentration (9.3 +/- 0.8 mg/dl versus 4.8 +/- 0.7 mg/dl) and the percentage glycated apo B (7.9 +/- 0.4% compared to 3.9 +/- 0.2%) were significantly higher in the diabetics than in non-diabetic controls (P less than 0.001). A positive correlation was found between the percentage of glycated apo B and glycated haemoglobin (r = 0.65; P less than 0.001) and fasting glucose concentration (r = 0.52; P less than 0.001) in diabetics. The percentage of glycated apo B in FH patients was not significantly different from controls, but the serum concentration of glycated apo B, because of the greatly increased total level of apo B was raised (8.2 +/- 1.4 mg/dl) to a similar extent to that of the diabetics.     

The role of human growth hormone in the regulation of cholesterol and bile acid metabolism

Cholesterol and bile acid metabolism was studied in 16 children with human GH (hGH) deficiency (11 with isolated hGH deficiency and 5 with multiple trophic hormone deficiency) before and after 6 months of hGH therapy. We measured plasma lipid concentrations, biliary lipid composition, and cholesterol saturation indices; calculated the bile acid pool size measured by the isotopic dilution technique using the stable isotope chenodeoxycholic-[11,12-d2] acid; and measured cholesterol and bile acid synthetic rates by sterol balance techniques. In all 16 patients, plasmas lipid concentrations were unchanged after hGH therapy; total plasma cholesterol was 182 +/- 10 (+/-SEM) mg/dl before and 179 +/- 9 mg/dl after treatment, high density lipoprotein-cholesterol was 47 +/- 2 mg/dl before and 49 +/- 3 mg/dl after treatment, low density lipoprotein-cholesterol was 112 +/- 10 mg/dl before and 111 +/- 8 mg/dl after therapy, and triglyceride was 113 +/- 13 mg/dl before and 107 +/- 10 mg/dl after hGH therapy. Biliary lipid composition and cholesterol saturation in 10 patients were similar to those in controls and unchanged with hGH therapy. Cholesterol synthesis (n = 14) was unchanged (7.6 +/- 1.4 vs. 9.6 +/- 1.2 mg/kg X day); however, bile acid synthesis (n = 15) increased from 3.1 +/- 0.4 to 4.3 +/- 0.6 mg/kg X day (P less than 0.025) after therapy. The chenodeoxycholate pool size (n = 8) was significantly reduced (P less than 0.025) before hGH treatment (416 +/- 64 mg/m2) compared to that in controls (617 +/- 45 mg/m2) and increased to 620 +/- 72 mg/m2 after hGH therapy (P less than 0.05). Chenodeoxycholate pool size expansion during hGH therapy was, at least in part, caused by an increase in hepatic bile acid synthesis. These findings suggest that hGH may indirectly modulate cholesterol metabolism through regulation of hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis.     

Plasma high density lipoprotein cholesterol in thyroid disease.

The plasma levels of high density lipoprotein cholesterol (HDL-C) were reduced in 16 hyperthyroid female patients compared to 37 euthyroid women (33.5 +/- 8 vs. 51.5 +/- 13 mg/dl (mean +/- SD); P less than 0.001). When 5 patients were restudied after restoration of the euthyroid state, plasma HDL-C increased from 29 +/- 5 to 43 +/- 11.5 mg/dl (P less than 0.05). In addition, in 22 hypothyroid women, HDL-C levels were also diminished compared to the euthyroid group (43.4 +/- 15.5 vs. 51.5 +/- 13 mg/dl; P less than 0.05). Nine patients were restudied after L-T4 replacement therapy; their levels of HDL-C increased but not to a statistically significant degree. The daily administration of 0.3 mg L-T4 to eight normal male volunteers for 1 month did not significantly affect HDL-C levels.     

Quantification of lipoprotein(a) and apolipoprotein(a) in plasma and lipoprotein fractions in the hypertriglyceridemic state.

Lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD) in particular in association with high low density lipoprotein (LDL) cholesterol concentrations. Hypertriglyceridemia on the other hand has been found to be associated with low Lp(a) values. This observation could be confirmed in 851 patients of the outpatient lipid clinic. Lp(a) median levels were 2.7-fold higher in patients with triglycerides below 200 mg/dl as compared with patients expressing triglyceride levels above 200 mg/dl (19 vs 7 mg/dl, P < 0.0001). In contrast to these data apolipoprotein(a) [apo(a)] has been detected in triglyceride-rich lipoproteins (TRL). To find out whether the presence of apo(a) in TRL is determined by the concentration of these particles, apo(a) concentrations were measured in TRL in fasting plasma of ten hypertriglyceridemic patients and ten normal controls with Lp(a) serum levels above 25 mg/dl. The apo(a) concentration in TRL did not show statistically significant differences between controls and patients (2.0+/-0.9 vs 1.8+/-1.6 mg/dl). In the second part of the study apo(a) levels in TRL were measured before and after fat feeding in eight healthy volunteers. Again no significant differences were observed in the apo(a) concentrations of the d < 1.006 a ml fraction before and after fat feeding (1.03+/-1.06 vs 0.81+/-0.63 mg/dl). In summary, this study fails to show an association of apo(a) with TRL for different states of hypertriglyceridemia. This negative finding is shown for constant particle numbers but might not be true if the particle number in TRL increases.     

Increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia

Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabolism. In order to further investigate the plasma metabolism of apoC-III in hypertriglyceridemic subjects, we have studied the plasma kinetics of VLDL apoC-III, HDL apoC-III and total plasma apoC-III with a primed constant intravenous infusion of deuterated leucine in a group of male patients with mixed hyperlipidemia (type IIb hyperlipoproteinemia, HLP, n=6) and in a group with type III HLP (n=6). Compared to normolipidemic control subjects (n=5), patients with type IIb and type III HLP had significantly higher levels of plasma TG (0.89 +/- 0.15 mmol/l vs 2.56 +/- 0.40 mmol/l vs 8.76 +/- 1.39 mmol/l, respectively, P <0.01), plasma apoC-III (9.5 +/- 0.8 mg/dl vs 20.8 +/- 2.5 mg/dl vs 41.7 +/- 5.6 mg/dl, P <0.01) and VLDL apoC-III (3.6 +/- 0.8 mg/dl vs 14.6 +/- 2.2 mg/dl vs 35.4 +/- 5.1 mg/dl, P <0.01). VLDL apoC-III production rates were significantly elevated in type IIb and type III patients (1.35 +/- 0.23 mg kg(-1) day(-1) vs 3.53 +/- 0.43 mg kg(-1) day(-1) vs 5.60 +/- 0.78 mg kg(-1) day(-1), P <0.01), as were total plasma apoC-III production rates (1.80 +/- 0.22 mg kg(-1) day(-1) vs 4.16 +/- 0.44 mg kg(-1) day(-1) vs 7.26 +/- 0.74 mg kg(-1) day(-1), P <0.01). VLDL apoC-III but not total plasma apoC-III fractional catabolic rates were reduced in type IIb and type III patients. Together with our previous results showing an increase of apoC-III production in patients with type IV HLP, and in overweight subjects with reduced insulin sensitivity, our data suggest that increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia.     

Plasma apolipoprotein B in middle-aged Finnish men. Evidence for a regional gradient of apo B and lack of negative correlation between apo B and dietary linoleate in hyperapobetalipoproteinemia

Plasma apolipoprotein B (apo B) concentrations were determined in 178 randomly selected 40-49-year-old men from Eastern and Southwestern Finland and compared with the concentrations of plasma lipids and the fatty acid composition of plasma and adipose tissue determined previously from the same populations. The plasma apo B concentrations ranged from 50 to 209 mg/dl. Although men from the two regions had similar mean concentrations of plasma triglyceride, total cholesterol and high density lipoprotein (HDL)-cholesterol, men from Eastern Finland had significantly higher mean apo B levels (139 +/- 25 mg/dl) and a lower ratio of total cholesterol to apo B (1.85 +/- 0.25) than the Southwestern men (125 +/- 33 mg/dl and 2.05 +/- 0.40, respectively). In the whole population, apo B and total cholesterol had significant negative correlations with the percentages of linoleate in the fatty acids of plasma and adipose tissue, which are known to reflect the quality of dietary fat. As the percentages of linoleate have previously been shown to be lower in the Eastern population, part of the regional difference in apo B is obviously explained by differences in the quality of dietary fat. On the other hand, men (n = 59) who had high plasma apo B (greater than 130 mg/dl) but low density lipoprotein (LDL)-cholesterol within the reference values (less than 5.17 mmol/l) showed no correlation between linoleate and apo B. This suggests that other factors than dietary fat determine the concentration of apo B in this group of men.     

The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes

OBJECTIVE: The purpose of the present study was to assess the impact of Mg + Zn, Vitamins C + E, and combination of these micronutrients on serum lipid and lipoprotein profiles in type 2 diabetic patients. MATERIALS AND METHODS: In a randomized, double-blind, placebo controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months; group M: 200 mg Mg and 30 mg Zn (n = 16), group V: 200mg Vitamin C and 150 mg Vitamin E (n = 18), group MV: minerals plus vitamins (n = 17), group P: placebo (n = 18). Fasting blood and urine samples were collected at the beginning and at the end of the trial. Serum triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were measured enzymatically. Apolipoproteins (apo) A1 and B were measured by immunoturbidimetric method. Adjustment for differences in baselines covariates and changes in variables during study were performed by analysis of covariance using general linear models. RESULTS: Results indicate that after 3 months of supplementation mean serum levels of HDL-c and apo A1 increased significantly in the MV group by 24% (50.4 +/-19.3 mg/dl versus 40.6 +/- 10.8 mg/dl) and 8.8% (169.8 +/- 33.8 mg/dl versus 156.1+ /- 23.9 mg/dl), respectively (P < 0.01). There were no significant changes in the levels of these parameters in the other three groups. Serum levels of total cholesterol, LDL-c, triglyceride, and apo B were not altered after supplementation in all four groups. CONCLUSION: It is concluded that since co-supplementation of Mg, Zn, Vitamins C and E significantly increases HDL-c and apo A1, supplementation of these micronutrients could be recommended for the type 2 diabetic patients based on their daily requirements.     

Serum apolipoprotein E in children and adolescents: the Bogalusa Heart Study

Serum apolipoprotein (apo) E levels and its relationship to lipids and lipoprotein cholesterol fractions were examined in a random subsample (n = 561) of children and adolescents (7 to 17 years of age) from a total biracial community. Mean (+/- SD) levels of apo E were higher in blacks (males 4.8 +/- 1.8 mg/dL; females 5.2 +/- 1.8 mg/dL) than in whites (males 3.9 +/- 1.2 mg/dL; females 4.3 +/- 1.0 mg/dL) irrespective of sex (P less than .001). The black-white difference in apo E persisted after controlling for the covariates: sexual maturation, age, adiposity, cigarette smoking, alcohol use, and oral contraceptive use (P less than .001). A sex differential (females greater than males, P less than .01) for apo E was seen in both racial groups. Apo E levels were inversely associated with age (P less than .01) and sexual maturation (P less than .05) only in white males. Apo E related positively and significantly to total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol fractions (HDL2-C and HDL3-C) in certain race-sex groups. Race, HDL2-C, triglycerides (very-low density lipoprotein cholesterol), HDL3-C, and sex were identified as predictor variables for apo E, in that order, and accounted for 21% of its variability in serum. It is conceivable that the observed race-sex differences in apo E may be related to apo E-HDL subfraction, which is thought to participate in the reverse cholesterol transport.     

Apolipoprotein levels in non-insulin-dependent diabetes mellitus with clinical macroangiopathy

To elucidate the changes of serum apolipoproteins as possible atherogenic factors in non-insulin-dependent diabetes mellitus (NIDDM), comparison was made between 47 NIDDM patients with clinical macroangiopathy (coronary heart disease and/or cerebral infarction) and 47 NIDDM patients without clinical macroangiopathy individually matched for age, sex, body mass index, glycemic control, mode of therapy, and blood pressure. Serum total cholesterol (223 +/- 63 mg/dl, mean +/- SD) and triglyceride (160 +/- 72 mg/dl) levels in NIDDM with clinical macroangiopathy were significantly higher than those (198 +/- 44 and 126 +/- 78 mg/dl) in control NIDDM. Apolipoprotein AII (apo AII) (28.8 +/- 6.9 mg/dl) in NIDDM with clinical macroangiopathy was significantly lower than that (31.4 +/- 5.5 mg/dl) in control NIDDM, and apo B (147 +/- 48 mg/dl) and apo CIII (13.1 +/- 5.9 mg/dl) in NIDDM with clinical macroangiopathy was significantly higher than that (113 +/- 35 and 10.8 +/- 4.7 mg/dl) in control NIDDM, respectively. There were no significant differences in apo AI, CII, and E levels. The ratio of HDL cholesterol to apo AI (0.36 +/- 0.08) and total cholesterol to apo B (1.6 +/- 0.3) in NIDDM with clinical macroangiopathy was significantly lower than that (0.40 +/- 0.09 and 1.8 +/- 0.4) in control NIDDM. These results suggest that abnormality of lipid metabolism is more significant in NIDDM with clinical macroangiopathy than in NIDDM without clinical macroangiopathy, and is more pronounced in women than in men.     

Total pancreatectomy increases the metabolic response to glucagon in humans

To evaluate the impact of glucagon deficiency on the response to glucagon replacement, we infused physiological doses of glucagon (1.25 ng/kg X min) into 9 totally pancreatectomized (PX) diabetic patients (C-peptide, undetectable) 1) for 24 h during their usual diet and insulin regimen and/or 2) for 6 h in a fasted insulin-withdrawn state. During both glucagon infusions, plasma glucagon rose from 46 +/- 2 (+/- SE) pg/ml (0-10% 3500 mol wt glucagon) to 112 +/- 9 pg/ml. In the 24-h study (n = 4), glucagon significantly increased mean 24-h glucose levels (272 +/- 27 mg/dl; P less than 0.05) and glycosuria (29 +/- 5 g/day; P less than 0.01) compared to preinfusion (158 +/- 14 mg/dl and 4 +/- 4 g/day, respectively) and postinfusion (200 +/- 35 mg/dl and 3 +/- 2 g/day) control periods. Blood ketones did not change. The 24-h glucagon infusion significantly lowered the fasting levels of the glucogenic amino acids aspartate (43%; P less than 0.01), threonine (46%; P less than 0.05), serine (46%; P less than 0.02), glycine (47%; P less than 0.01), and methionine (34%; P less than 0.02). Fasting alanine levels decreased from 835 +/- 236 to 393 +/- 66 microM (P less than 0.05). The 6-h glucagon infusion caused a 101 +/- 14 mg/dl maximal plasma glucose increment in PX (n = 8) vs. 33 +/- 11 in 5 insulin-withdrawn type I diabetic patients serving as controls (P = 0.022). Furthermore, when glucagon was infused at a higher rate (3 ng/kg X min) in 12 additional type I diabetic patients, the mean maximal plasma glucose increment (54 +/- 15 mg/dl) was still less than half that in PX, despite a 3-fold higher infusion plasma glucagon level (326 +/- 37 pg/ml). The 6-h glucagon infusion caused a significant decrease in the concentrations of glucogenic amino acids in the glucagon-deficient patients, but not in the type I diabetic patients. We conclude that 1) glucagon replacement in the PX patient markedly alters blood glucose and glucogenic amino acids, but not ketone levels; and 2) the metabolic response to glucagon is considerably more pronounced in PX patients than in type I diabetic patients. These data suggest that glucagon responsiveness is enhanced in the chronic hormone-deficient state.     

Changes in lipoprotein composition in hypertriglyceridemic patients taking cholesterol-free fish oil supplements

Fish oils rich in n - 3 fatty acids (FAs) have been shown to markedly lower levels of very low density lipoproteins (VLDL), but not the low density lipoproteins (LDL) which are derived from VLDL. Changes in the size and chemical composition of lipoproteins may affect their metabolism. In order to examine the effects of n - 3 FAs on lipoprotein metabolism, 6 patients with hypertriglyceridemia were given 6 g n - 3 FAs/day. Plasma lipid and apoprotein (apo A-I, A-II, B, E, C-II, C-III) levels (mg/dl) were measured before and after 4 weeks of treatment. Changes in lipoprotein size were assessed by gel chromatography. n - 3 FAs lowered VLDL cholesterol (58 +/- 35 to 40 +/- 30, P less than 0.01) and total triglyceride (410 +/- 170 to 236 +/- 114, P less than 0.01). In spite of this, LDL cholesterol levels did not decrease, and apo B levels increased (98 +/- 28 to 111 +/- 27, P less than 0.05). HDL cholesterol rose (31 +/- 5 to 34 +/- 7, P less than 0.05). The lipid content of smaller VLDL particles was reduced by over 40%, but the protein content was largely unchanged. Large triglyceride-rich lipoprotein particles were reduced to a greater extent than were small particles. These changes in VLDL particle size and composition may enhance the synthesis of LDL in hypertriglyceridemic patients taking n - 3 FA supplements.     

Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics.

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.     

Effect of lovastatin on hemorheology in type II hyperlipoproteinemia

To assess the effect of lovastatin on blood rheology, the hemorheological determinants fibrinogen, red cell aggregation, plasma viscosity, hematocrit and platelet aggregation (spontaneous and ADP-induced) were studied in 15 patients with type II hyperlipoproteinemia in the course of treatment with lovastatin. Prior to therapy, fibrinogen (Fgen), red cell aggregation (RCA-S, RCA-L) and plasma viscosity (PV) as well as cholesterol (Chol) and triglycerides (Tg) were increased in the hyperlipemic patients compared with healthy normolipemic controls (Fgen: 319.3 +/- 65 vs. 269.8 +/- 48 mg/dl; RCA-S: 7.93 +/- 1 vs. 6.62 +/- 1, RCA-L: 9.86 +/- 1 vs. 7.8 +/- 1 arbitrary units; PV: 1.75 vs. 1.63 mPa/s; Chol: 317.0 +/- 32 vs. 176.5 +/- 21 mg/dl; Tg: 154.5 +/- 88 vs. 72.8 +/- 16 mg/dl; all P less than 0.05). Three months of treatment with lovastatin resulted in a marked decrease in red cell aggregation and plasma viscosity, parallel to a fall in cholesterol (the following pretreatment values were monitored after a standard lipid-lowering diet; RCA-S: 7.59 +/- 1 vs. 6.65 +/- 0.9, RCA-L: 9.34 +/- 1 vs. 8.15 +/- 1 arbitrary units; PV: 1.74 vs. 1.65 mPa/s; Chol: 309.8 +/- 41 vs. 217.1 +/- 30 mg/dl; all P less than 0.01); fibrinogen however, remained unchanged throughout the treatment period (346.4 +/- 73.3 vs. 330.5 +/- 70.2 mg/dl, n.s.). No differences were seen in hematocrit and platelet aggregability between hyperlipemic patients and controls and no changes occurred in these parameters during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Remnant-like lipoprotein particle level and insulin resistance are associated with in-stent restenosis in patients with stable angina

BACKGROUND: The aim of this study was to evaluate the independent effect of serum remnant-like lipoprotein particle level and insulin resistance on in-stent restenosis in nondiabetic patients with stable angina. METHODS: The study included 64 nondiabetic patients with stable angina who underwent successful coronary stenting. At the time of stenting, we evaluated the patients' lipid profiles including remnant-like lipoprotein particles cholesterol, plasma glucose and insulin levels, and insulin resistance by the homeostasis model assessment. RESULTS: There was no significant difference in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels between two patient groups with (n=15) and without (n=49) in-stent restenosis. Plasma remnant-like lipoprotein particles cholesterol level was significantly higher in patients with restenosis than in patients without restenosis (8.2+/-7.0 mg/dl vs. 4.5+/-2.6 mg/dl, P=0.006). Although plasma glucose level was similar between the two groups, insulin level and homeostasis model assessment were significantly higher in patients with restenosis, compared with those without restenosis (11.2+/-12.4 vs. 7.1+/-2.8, P=0.039; and 2.6+/-2.9 vs. 1.7+/-0.7, P=0.040, respectively). In multivariate logistic regression analysis, plasma remnant-like lipoprotein particles cholesterol level (>4.8 mg/dl; the 75th percentile of the distribution of remnant-like lipoprotein particles cholesterol level) was the independent predictor of in-stent restenosis (odds ratio: 8.15; confidence interval: 1.02-65.16; P=0.048). CONCLUSIONS: Our findings suggest that high serum remnant-like lipoprotein particles cholesterol level, and not insulin resistance may be an independent risk factor on in-stent restenosis in nondiabetic patients with stable angina.     

Zinc status of children with sickle cell disease: relationship to poor growth

We examined the zinc status of 80 children with sickle cell disease (SCD) and 44 disease-free sibling controls aged 3 to 18 years. For both patients and controls, variations in serum zinc by age, type of hemoglobinopathy, and growth status were measured. The mean serum zinc concentration of patients was significantly lower than for controls (77.8 +/- 9.9 vs. 82.2 +/- 9.8 micrograms/dl, mean +/- 1SD, P less than .05). Serum levels of alkaline phosphatase (AP) and retinol-binding protein (RBP), two zinc-dependent proteins, were also lower among patients (AP: 171 +/- 66 vs. 243 +/- 97 IU/L, P less than .001; RBP: 1.92 +/- .9 vs. 2.77 +/- .9 mg/dl, P less than .001). Patients greater than or equal to 12 years of age (n = 34) had significantly lower zinc levels than those less than 12 years (74.5 +/- 8.4 vs. 80.3 +/- 10.3 micrograms/dl, P less than .01), and children with homozygous SCD (Hb SS, n = 55) had a more pronounced deficiency than those with a variant hemoglobinopathy (76.3 +/- 8.9 vs. 81.5 +/- 11.5, micrograms/dl, P less than .05). Patients classified as having "poor" growth (height-for-age less than 5th percentile, n = 24) had a lower serum zinc level than those with "normal" growth (72.8 +/- 8.0 vs. 79.8 +/- 10.0 micrograms/dl, P less than .01). Dietary intake data, body mass index, and serum total protein and albumin levels were similar for patients and controls, suggesting that zinc deficiency in SCD does not relate to inadequate dietary intake. The origin of low serum zinc levels in children with SCD is more likely to relate to factors such as increased urinary zinc excretion, chronic intravascular hemolysis, and/or zinc malabsorption.     

Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome

Twenty-nine patients with polycystic ovary syndrome (PCOS) and 30 normal women had lipoprotein lipid and androgen profiles compared after a 12-h fast. Both PCOS and normal women were evaluated in the proliferative phase of the cycle. PCOS patients had higher serum LH to FSH ratios [2.0 +/- 1.3 (+/- SEM) vs. 0.6 +/- 0.1), higher testosterone (T; 66 +/- 5 vs. 33 +/- 2 ng/ml), higher free T (1.1 +/- 1 vs. 0.4 +/- 0.02 ng/dl), and higher dehydroepiandrosterone sulfate (291 +/- 28 vs. 140 +/- 12 micrograms/dl) levels, and lower T-estrogen-binding globulin-binding capacity (1.5 +/- 0.2 vs. 2.2 +/- 0.1 micrograms/dl) than normal women (all P less than 0.05). The PCOS patients had higher mean serum triglycerides [122 +/- 11 (+/- SEM) 63 +/- 3 mg/dl] and very low density lipoprotein cholesterol levels (24 +/- 2 vs. 13 +/- 1 mg/dl), but lower high density lipoprotein cholesterol levels (43 +/- 2 vs. 58 +/- 2 mg/dl; P less than 0.05). While PCOS patients were heavier and more sedentary and their diets were higher in saturated fat and lower in fiber (P less than 0.01, respectively), the differences in lipoprotein lipid concentrations could not be attributed to body weight. T-estrogen-binding globulin-binding capacity correlated with high density lipoprotein cholesterol in PCOS patients (r = 0.42; P = 0.025) after adjusting for weight. We conclude that hyperandrogenemia in women may result in a male pattern of lipoprotein lipid concentrations. These findings suggest that PCOS patients may have increased atherogenic potential.     

LDL concentration is correlated with the removal from the plasma of a chylomicron-like emulsion in subjects with coronary artery disease

In animal model studies, the uptake of chylomicron remnants after entering in the space of Disse occurs mainly by low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP). In subjects, the relative importance of each one of these receptors for the clearance of chylomicron remnants is not fully understood. In our study, LDL cholesterol and apolipoprotein (apo) B were correlated to the plasma kinetics of a chylomicron-like emulsion in 77 subjects (11 women, mean age 58 +/- 12 years) with coronary artery disease (CAD). Their total cholesterol was 227 +/- 25 mg/dl, triglyceride 159 +/- 25 mg/dl, LDL cholesterol 148 +/- 27 mg/dl, HDL cholesterol 40 +/- 9 mg/dl, apo A1 1.80 +/- 0.53 g/l and apo B 1.65 +/- 0.48 g/l. The emulsion was double-labeled with 3H-triolein and 14C-cholesteryl oleate and injected intravenously after 12-h fasting. The decay curves of the radioisotopes were determined from blood samples collected at predetermined intervals during 60 min. A negative correlation between FCR of the emulsion cholesterol esters and LDL cholesterol and apo B plasma concentrations was found (r=-0.4, P=0.005 and r=-0.3, P=0.01, respectively) whereas FCR of the emulsion triglycerides did not correlate with any of the plasma lipids or apolipoprotein parameters. Concluding, in patients with CAD, LDL catabolic pathway significantly influences the removal from plasma of chylomicron remnants.     

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects.

AIMS: We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes. METHODS: A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non-diabetic patients with CAD, and 358 controls were enrolled. RESULTS: Diabetic patients with CAD showed Lp(a) levels (21.2 +/- 17.7 vs. 15.1 +/- 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28-3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30-8.60). Lp(a) levels (30.2 +/- 23.7 vs. 21.2 +/- 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non-diabetic subjects. Diabet. Med. 18, 589-594 (2001)