Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis (RA) frequently display an atherogenic lipid profile which has been linked with inflammation. Tumor necrosis factor-alpha (TNF-alpha), a pivotal pro-inflammatory cytokine in RA may be involved in the development of the disturbed lipid metabolism. We investigated whether infliximab, an anti-TNF-alpha therapy, may modify the lipid profile. METHODS: 56 consecutive RA patients were treated with infliximab (3 mg/kg at weeks 0, 2, 6, 14, 22, 30). Lipid profile and CRP were assayed at baseline and before infusion at weeks 6 and 30. Baseline values were compared with those in 56 healthy volunteers. RESULTS: At baseline, the concentrations of HDL-cholesterol were lower in RA patients than in the controls (1.3+/-0.4 vs. 1.5+/-0.2 mmol/L; p<0.01). The triglyceride concentrations (1.6+/-0.8 vs. 1.3+/-0.4 mmol/L, p<0.01), the ratio of total cholesterol/HDL-cholesterol (4.3+/-1.6 vs. 3.2+/-0.5, p<0.001) and LDL-cholesterol/HDL-cholesterol (2.6+/-1.2 vs. 1.7+/-0.5, p<0.001) were significantly higher in RA patients than in controls. After 6 weeks of infliximab therapy, the mean total cholesterol concentration increased by 25% (p<0.001), LDL-cholesterol by 24% (p<0.001) and HDL-cholesterol by 30% (p<0.001). The decrease in CRP levels to 30 week inversely correlated with the increase in HDL-cholesterol (r=-0.47, p=0.005). CONCLUSIONS: Infliximab administration is associated with important increases in cholesterol levels in all its forms but as no significant beneficial effect on the atherogenic ratio.     

Validation of the Friedewald Equation for Evaluation of Plasma LDL-Cholesterol

In most clinical laboratories, low density lipoprotein (LDL) cholesterol is usually estimated indirectly with the Friedewald equation or directly with the N-geneous assay. We assessed LDL-cholesterol values obtained by both methods to find an appropriate fasting period and to assess the influence of the energy content of the last meal. Blood samples were taken from 28 healthy volunteers who had consumed a standard meal (107 g of carbohydrate, 658 kcal) followed by a fasting period of 12 and 18 h, or a high-energy meal (190 g of carbohydrate, 1011 kcal) with a fasting period of 12 h. Prolongation of the fasting period from 12 h to 18 h decreased glucose level, but did not decrease triacylglycerol, total cholesterol, or high density lipoprotein (HDL) cholesterol. LDL-cholesterol levels measured with the N-geneous assay did not change (94.0 +/- 21.5 to 96.3 +/- 19.1 mg/dl). LDL-cholesterol levels calculated with the Friedewald equation were also similar after fasting periods of 12 h (98.5 +/- 21.4 mg/dl) and 18 h (99.7 +/- 20.2 mg/dl). The high-energy meal did not change the level of LDL-cholesterol measured with the N-geneous assay (96.1 +/- 21.2 mg/dl), or the glucose, triacylglycerol, total cholesterol, or HDL-cholesterol level, but LDL-cholesterol levels evaluated from the Friedewald equation (92.6 +/- 20.3 mg/dl) became significantly lower. A fasting time longer than 12 h is not necessary to obtain reasonable blood lipid levels. The Friedewald equation gave higher LDL-cholesterol levels than N-geneous assay in young Japanese females who had eaten a low-energy meal, and lower values when they had eaten a high-energy meal. Thus, it may be necessary to pay attention to energy of nigh meal prior to blood withdrawal.     

Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet

OBJECTIVE: To investigate the tolerability, efficacy, and mode of action of Caiapo, an extract of white sweet potatoes, on metabolic control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 61 type 2 diabetic patients treated by diet were given 4 g Caiapo (n = 30; mean age 55.2 +/- 2.1 years; BMI 28.0 +/- 0.4 kg/m(2)) or placebo (n = 31; mean age 55.6 +/- 1.5 years; BMI 27.6 +/- 0.3 kg/m(2)) once daily for 12 weeks. Each subject underwent a 75-g oral glucose tolerance test (OGTT) at baseline and after 1, 2, and 3 months to assess 2-h glucose levels. Additionally, fasting blood glucose, HbA(1c), total cholesterol, and triglyceride levels were measured. RESULTS: After treatment with Caiapo, HbA(1c) decreased significantly (P < 0.001) from 7.21 +/- 0.15 to 6.68 +/- 0.14%, whereas it remained unchanged (P = 0.23) in subjects given placebo (7.04 +/- 0.17 vs. 7.10 +/- 0.19%). Fasting blood glucose levels decreased (P < 0.001) in the Caiapo group (143.7 +/- 1.9 vs. 128.5 +/- 1.7 mg/dl) and did not change in the placebo group (144.3 +/- 1.9 vs. 138.2 +/- 2.1 mg/dl; P = 0.052). A decrease in body weight was observed in both the placebo group (P = 0.0027) and in the Caiapo group (P < 0.0001), probably due to a better- controlled lifestyle. In the Caiapo group, body weight was related to the improvement in glucose control (r = 0.618; P < 0.0002). Two-hour glucose levels were significantly (P < 0.001) decreased in the Caiapo group (193.3 +/- 10.4 vs. 162.8 +/- 8.2 mg/dl) compared with the placebo group (191.7 +/- 9.2 vs. 181.0 +/- 7.1 mg/dl). Mean cholesterol at the end of the treatment was significantly lower in the Caiapo group (214.6 +/- 11.2 mg/dl) than in the placebo group (248.7 +/- 11.2 mg/dl; P < 0.05). No significant changes in triglyceride levels or blood pressure were observed, and Caiapo was well tolerated without significant adverse effects. CONCLUSIONS: This study confirms the beneficial effects of Caiapo on plasma glucose as well as cholesterol levels in patients with type 2 diabetes. For the first time, the long-term efficacy of Caiapo on glucose control was demonstrated by the observed decrease in HbA(1c). Thus, the neutraceutical Caiapo seems to be a useful agent in the treatment of type 2 diabetes.     

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.     

Enhanced nitric oxide production is closely associated with serum lipid concentrations in adolescents

BACKGROUND: To investigate whether nitric oxide (NO) production is associated with serum lipid concentrations and body mass index (BMI), we measured serum nitrate and nitrites (NOx) concentrations, serum lipid profiles, and anthropometric parameters in 319 adolescents. METHODS: Serum NOx concentrations were determined using the Griess reaction. Serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by standard enzymatic procedures. RESULTS: Subjects with increased serum cholesterol or triglyceride concentrations exhibited remarkably high NOx levels. Total cholesterol and triglyceride averaged 161.5+/-27.4 and 205.9+/-107.8 mg/dl in males with NOx >92.8 micromol/l (upper 20%), which were significantly above the values (132.4+/-17.2 and 58.1+/-20.3 mg/dl) in those with NOx <15.6 micromol/l (lower 20%). The prevalences of male adolescents with increased concentrations of cholesterol and triglyceride were significantly higher in the subjects with NOx > or =51.2 micromol/l than in those with NOx <51.2 micromol/l (8.9% and 22.2% vs. 1.6% and 2.3%, p<0.05, respectively). Correlation coefficients of serum lipid concentrations and anthropometric parameters vs. serum NOx concentrations were higher in males than in females for cholesterol (r=0.28 vs. 0.23), triglyceride (r=0.51 vs. 0.42), HDL-C (r=-0.25 vs. -0.16), and BMI (r=0.39 vs. 0.27). CONCLUSIONS: NO production is closely associated with serum lipid concentrations in adolescents, and these associations are stronger in males than in females.     

Effects of replacing saturated fat with complex carbohydrate in diets of subjects with NIDDM

This study examined the safety of an isocaloric high-complex carbohydrate low-saturated fat diet (HICARB) in obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Although hypocaloric diets should be recommended to these patients, many find compliance with this diet difficult; therefore, the safety of an isocaloric increase in dietary carbohydrate needs assessment. Lipoprotein cholesterol and triglyceride (TG, mg/dl) concentrations in isocaloric high-fat and HICARB diets were compared in 7 NIDDM subjects (fat 32 +/- 3%, fasting glucose 190 +/- 38 mg/dl) and 6 nondiabetic subjects (fat 33 +/- 5%). They ate a high-fat diet (43% carbohydrate; 42% fat, polyunsaturated to saturated 0.3; fiber 9 g/1000 kcal; cholesterol 550 mg/day) for 7-10 days. Control subjects (3 NIDDM, 3 nondiabetic) continued this diet for 5 wk. The 13 subjects changed to a HICARB diet (65% carbohydrate; 21% fat, polyunsaturated to saturated 1.2; fiber 18 g/1000 kcal; cholesterol 550 mg/day) for 5 wk. NIDDM subjects on the HICARB diet had decreased low-density lipoprotein cholesterol (LDL-chol) concentrations (107 vs. 82, P less than .001), but their high-density lipoprotein cholesterol (HDL-chol) concentrations, glucose, and body weight were unchanged. Changes in total plasma TG concentrations in NIDDM subjects were heterogeneous. Concentrations were either unchanged or had decreased in 5 and increased in 2 NIDDM subjects. Nondiabetic subjects on the HICARB diet had decreased LDL-chol (111 vs. 81, P less than .01) and unchanged HDL-chol and plasma TG concentrations).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lipids in Iranians with sickle cell disease: hypocholesterolemia in sickle cell anemia and increase of HDL-cholesterol in sickle cell trait

BACKGROUND: The metabolism of lipids may be altered in sickle cell anemia and beta-thalassemia patients. METHODS: Plasma lipids in 24 patients with sickle cell anemia (SS), 15 patients with sickle/beta-thalassemia (ST), 19 individuals with sickle cell trait (AS) and 62 healthy individuals (AA) were measured. RESULT: Total cholesterol concentrations in both sexes with sickle cell anemia (SS males: 104.7, SS females: 142.7 mg/dl) and sickle/beta-thalassemia (ST males: 116.7, ST females: 137.5 mg/dl) were lower (P<0.05) than AS (AS males: 171.5, AS females: 185.4 mg/dl) and normal individuals (AA males: 173.7, AA females: 183.0 mg/dl). The mean HDL-cholesterol in males with SS (35.6 mg/dl) and ST (40.7 mg/dl) were (P=0.001) lower than AS males (58.9 mg/dl). However, the mean HDL-cholesterol in females with SS (43.2 mg/dl) was lower (P<0.001) than AS females (62.7 mg/dl). The mean LDL-cholesterol of males with SS (53.8 mg/dl) was lower (P<0.01) than AS (89.4 mg/dl) and control males (115.9 mg/dl). Males with ST had a lower (P<0.001) LDL-cholesterol (58.0 mg/dl) compared to control males. In females with SS the LDL-cholesterol (78.3 mg/dl) was lower (P<0.001) than control females (124.3 mg/dl). However, females with ST had lower (P<0.05) LDL-cholesterol (61.6 mg/dl) than AS (101.7 mg/dl) and control females. There was no significant difference in total concentrations of cholesterol and triglycerides between males and females with AS and those with normal hemoglobin. However, the HDL-cholesterol in both genders with AS was higher (P<0.001) than normal subjects. Also, the concentration of LDL-cholesterol in both males and females with AS was lower than control males (P<0.05) and females. CONCLUSIONS: Hemolytic stress could be associated with a significant reduction in plasma lipids and lipoproteins. It appears that patients with sickle cell anemia and individuals with sickle cell trait are at a lower risk for coronary artery disease.     

Hemorheology and H.E.L.P. in multi-infarct dementia]

Some papers report that the effect of heparin-mediated extracorporeal LDL less than cholesterol, LP(a), triglycerides, fibrinogen greater than precipitation (H.E.L.P.) in cardiovascular disease may results from an influence on the above-mentioned parameters. Hence, this method has been applied in multi-infarct dementia (MID), where fibrinogen, whole blood and plasma viscosity and red cell transit time (RCTT) are increased. The selection of patients was based on DMS-3, on NINCDS/ADRDA criteria and on the Hachinski Ischemic Stroke Scale. All the patients (n = 14) were examined magnet resonance imaging. Fibrinogen, cholesterol, LDL-cholesterol, HDL-cholesterol, LP(a), RCTT and plasma and whole blood viscosity were determined prior to, and after each two H.E.L.P. procedures. Fibrinogen was lowered (in a comparison of the data prior to the first and following the second plasmapheresis) from 526.4 +/- 114 to 314.1 +/- 80.1 mg/dl (p less than 0.01), cholesterol from 210.8 +/- 76.8 to 131.3 +/- 38.2 mg/dl (p less than 0.01), LDL from 125 +/- 53 mg/dl to 63.6 +/- 25.7 mg/dl (p less than 0.01), LP(a) from 26.2 +/- 13.2 to 12.0 +/- 9.5 mg/dl (p less than 0.01), HDL from 31.7 +/- 6.3 to 29.7 +/- 5.6 mg/dl (no significance), RCTT from 14.4 +/- 2.8 to 10.9 +/- 0.9 (p less than 0.01), whole blood viscosity (low shear rate) from 11.64 +/- 1.7 to 8.74 +/- 1.4 mPa/sec (p less than 0.01) and (high shear rate) from 5.38 +/- 0.58 to 4.28 +/- 0.83 mPa/sec (p less than 0.01). Plasma viscosity decreased from 1.51 +/- 0.12 mPa/sec to 1.25 +/- 0.1 mPa/sec (p less than 0.05). In cases of MID the implementation of H.E.L.P. therefore enabled an alteration of the hemorheological profile which has so far not been achieved by any hemorheologically active substance to a comparable degree and in comparable time.     

Relation of hyperlipidemia in serum and loss of high density lipoproteins in urine in the nephrotic syndrome

The mechanism leading to hyperlipidemia in the nephrotic syndrome is not fully understood but may be related in part to loss of high density lipoproteins in the urine of patients with nephrosis. To prove this hypothesis, we compared serum lipoprotein profiles with the excretion of high density lipoproteins in urine in 19 nephrotic patients. Serum cholesterol ranged from 19-152 (median value 45) mg/dl in very low density lipoproteins (VLDL), from 130-443 (median 186) mg/dl in low density lipoproteins (LDL) and from 19-64 (median 33) mg/dl in high density lipoproteins (HDL). Hyperlipoproteinemia was found in 17 patients, which was classified as phenotype IIa (Fredrickson) in 2, as phenotype IIb in 9 and as phenotype IV in 6 subjects. Two patients showed normal lipoprotein patterns. VLDL- and LDL-cholesterol were not found in detectable amounts in urine, whereas HDL-cholesterol was measured in low concentrations from 0.1-8.3 mg/24 h in all samples. There was no correlation between serum HDL-cholesterol and urinary HDL-cholesterol, but a positive correlation between serum LDL-cholesterol and urinary HDL-cholesterol (r = +0.54, p less than 0.05). However, the total amount of the daily urinary loss of HDL (less than 1% of total plasma HDL) seems not to be sufficient to explain hyperlipoproteinemia in the nephrotic syndrome.     

Abnormal capacity to induce cholesterol efflux and a new LpA-I pre-beta particle in type 2 diabetic patients

In this study, we first characterized the lipoprotein components of serum samples obtained from a group of well-controlled diabetic patients and from healthy subjects in fasting and postprandial states. We then explored some aspects of reverse cholesterol transport in the same population. Patients showed high levels of fasting triglycerides, postprandial triglyceride responses and LpC-III levels (3.18+/-0.86 vs 2.17+/-0.54 mg/dl, P < 0.001). There were also positive correlations between LpC-III and fasting triglycerides (r = 0.82, P < 0.001), total triglyceride area (r = 0.75, P < 0.001) and incremental triglyceride area (r = 0.54, P < 0.001). HDL-C and apo A-I were significantly decreased in diabetic patients due to a selective reduction in LpA-I subfraction, whose antiatherogenic role is generally accepted (37.4+/-8.0 vs 49.2+/-12.5 mg/dl, P < 0.001). In addition, HDL from patients proved to be triglyceride enriched and cholesteryl ester depleted, alterations which were further amplified in the postprandial state. The molar ratio HDL-C/apo A-I + apo A-II, already defined as a predictor of apo A-I fractional catabolic rate, was significantly diminished in the patient group (15.1+/-2.2 vs 20.8+/-3.3, P < 0.001), thus suggesting an accelerated catabolism of apo A-I. For the first time, we describe here the presence of a small apo A-I-containing particle, isolated by two-dimensional electrophoresis and characterized by immunoblotting, only in samples from diabetic patients. This particle that we named pre-beta0, has an apparent molecular weight of 40 kDa. As regards the capacity of serum samples to promote cholesterol efflux from [3H]cholesterol-labeled Fu5AH rat hepatoma cells, patient samples were found to induce significantly lower cholesterol efflux than controls only in the postprandial state (21.2+/-3.3 vs 23.8+/-1.8%, P = 0.012). The presence of pre-beta0 in samples from diabetic patients might therefore be associated to an altered capacity of these serum samples to promote cellular cholesterol efflux. Overall, these abnormalities may contribute to a delay in the reverse cholesterol transport pathway in type 2 diabetic patients.     

Intravenous anti TNF-alpha antibody therapy leads to elevated triglyceride and reduced HDL-cholesterol levels in patients with rheumatoid and psoriatic arthritis

BACKGROUND & AIMS: We investigated the effect of Infliximab, an anti TNF-alpha antibody, on plasma lipids and lipoproteins in patients with rheumatoid arthritis and psoriatic arthritis. METHODS: Five male and 10 female patients with a mean age of 56.7 years were included in this study. Seven of the patients were diagnosed with rheumatoid arthritis and 8 patients with psoriatic arthritis. All patients received infusions of 3 mg/kg Infliximab (at week 0, 2 and 6). Lipids, lipoproteins and standard clinical parameters were assessed at baseline (0 week), after 2 weeks, and in 4 patients after 6 weeks. RESULTS: There was a significant increase in triglyceride levels during treatment with Infliximab (112 +/- 48 versus 133 +/- 53 mg/dl, p < 0.01). In contrast, HDL-cholesterol levels were significantly lowered (56 +/- 12 versus 50 +/- 13 mg/dl, p < 0.006) by the treatment. There was no significant difference in total cholesterol (209 +/- 25 versus 205 +/- 36 mg/dl) or in LDL-cholesterol (131 +/- 24 versus 118 +/- 43 mg/dl) before and after treatment. Similarly, lipoprotein(a) levels did not alter during treatment (median: 1.1 versus 1.4 mg/dl). CONCLUSION: This study shows that intravenous Inflixmab therapy leads to changes in plasma lipid and lipoprotein levels in patients with rheumatoid and psoriatic arthritis and may result in a more atherogenic lipid and lipoprotein profile. Although larger patient numbers need to be studied to confirm our findings, these results suggest that lipid levels should be checked and monitored in patients receiving infliximab therapy, particularly in patients with vascular disease.     

Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians.

The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio.     

Comparison between lovastatin and cholestyramine in the treatment of moderate to severe primary hypercholesterolaemia.

120 patients (64 men, 56 women) aged 19-66 years with primary hypercholesterolaemia (mean serum total cholesterol 10.1 mmol/l, range 6.5-16.3 mmol/l) with normal or moderately raised concentrations of serum triglycerides were randomised after four weeks' diet and four weeks' diet+placebo phase either to cholestyramine (40 patients) or lovastatin (80 patients) treatments for the succeeding 12 weeks. The maximal daily doses were 24 g of cholestyramine and 80 mg of lovastatin. The baseline data of the treatment groups were comparable with the exception of HDL-cholesterol concentrations, which were lower in the lovastatin group. The mean reductions in total serum cholesterol concentrations were 24.3% for cholestyramine (P less than or equal to 0.01) and 33.4% for lovastatin (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), in LDL-cholesterol 32.1% (P less than or equal to 0.01) and 40.7% (P less than or equal to 0.01) (P less than or equal to 0.05 between the treatment groups) and in apolipoprotein B 23.3% (P less than or equal to 0.01) and 33.3% (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), respectively. Lovastatin was the only drug to reduce serum triglyceride concentrations, it did so by 26.0%. HDL-cholesterol increased by 7.7% (P = NS) when cholestyramine was taken and by 13.5% (P less than or equal to 0.05) with lovastatin (P = NS between the treatment groups). Apolipoprotein A1 remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk factors of atherosclerosis--primary examination of Vienna employees]

In the course of an atherosclerosis intervention study, a basic medical check-up of 2105 out of 4800 employees of a Viennese banking house was carried out (37.1 +/- 11.0 years, 54.6% females). Apart from liver and kidney function parameters, an extensive lipid status was determined, the blood pressure was measured, and a cardiovascular-centered case history ascertained. The mean cholesterol level in females was 208.3 +/- 54 mg/dl and that in males was 226.8 +/- 61.1 mg/dl. The HDL-cholesterol level in males was 43.8 +/- 11.9 mg/dl; that in females (54.9 +/- 13.4 mg/dl) was significantly higher. The mean value of LDL-cholesterol in the entire group was 141.6 +/- 51.4 mg/dl and it was significantly higher in males, as well as in participants with known hypertension. 33.4% of the persons stated that they smoked. The obtained data will serve not only to discover potential interrelations between the individual risk factors of atherosclerosis in Austria, but also in particular as a basis for interventional strategies on the part of the company's medical services.     

Low-dose effect of simvastatin (MK-733) on serum lipids, lipoproteins, and apolipoproteins in patients with hypercholesterolemia

The effects of simvastatin (MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipids, lipoproteins, and apolipoproteins were investigated in 29 patients (12 men, 17 women, aged 37 to 73) with moderate to severe hypercholesterolemia. It was given in doses of 2.5 mg/day for four months and 5 mg/day for the succeeding four months. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B decreased by 18% (263 +/- 7 mg/dl to 216 +/- 7 mg/dl, P less than 0.01), 24% (180 +/- 7 mg/dl to 136 +/- 7 mg/dl, P less than 0.01), and 21% (133 +/- 4 mg/dl to 104 +/- 3 mg/dl, P less than 0.01), respectively, four months after treatment. Similar reductions (17%, 24%, and 23%, respectively, P less than 0.01) were observed at eight months. A significant reduction in triglyceride (TG) was observed (173 +/- 15 mg/dl to 136 +/- 11 mg/dl at eight months, P less than 0.01), as was a significant increase in serum high-density lipoprotein cholesterol (HDL-C) (48 +/- 2 mg/dl to 52 +/- 2 mg/dl at eight months, P less than 0.01). However, apo AI and apo AII remained unchanged. Atherogenic indices of (TC--HDL-C)/ HDL-C, LDL-C/HDL-C, and apo B/Apo AI ratios were significantly (P less than 0.01) reduced after treatment. No significant changes were observed in lipoprotein lipase, hepatic TG lipase, and lecithin: cholesterol acyltransferase (LCAT) activities. Simvastatin was well tolerated and no critical side effects were noted in the eight-month study period. These data indicate that simvastatin, even at a low dose of 2.5 to 5 mg daily, causes consistent reductions in serum TC, LDL-C, apo B, and TG, and a rise in HDL-C and antiatherogenic lipoproteins.     

Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence

The objective of this study was to determine vitamin D supplementation effects on concentrations of atorvastatin and cholesterol in patients. Sixteen patients (8 men, 8 women; 10 Caucasians, 4 African Americans, 1 Hispanic, 1 Asian), aged 63 +/- 11 years (mean +/- SD, weight 92 +/- 31 kg) on atorvastatin (45 +/- 33 mg/day) were studied with and without supplemental vitamin D (800 IU/day for 6 weeks). Levels of vitamin D (1,25-dihydroxy(OH) and 25 OH-metabolites), atorvastatin (parent, OH-acid metabolites, lactone, and lactone metabolites), and cholesterol (total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol) were determined at 0.5, 3, and 10 h after dosing. Vitamin D supplementation increased vitamin D-25-OH metabolites (P < 0.0001) without increased 1,25-dihydroxy vitamin D. Atorvastatin and active metabolite concentrations (P < 0.001) as well as LDL-cholesterol and total-cholesterol levels (97 +/- 28 mg/dl vs. 83 +/- 30 and 169 +/- 35 mg/dl vs. 157 +/- 37, P < 0.005) were lower during vitamin D supplementation. The conclusion of the study is that vitamin D supplementation lowers atorvastatin and active metabolite concentrations yet has synergistic effects on cholesterol concentrations.     

Significance of low density lipoprotein production in the regulations of plasma cholesterol level in man.

To determine whether production or catabolism of low density lipoprotein (LDL) is the major factor controlling LDL concentrations in subjects with plasma cholesterol levels from low-normal to mildly elevated, measurements of apoprotein of LDL (apoLDL) turnover were performed in 16 patients with various plasma cholesterol concentrations. Cholesterol balance studies were done simultaneously in 13 of these patients. Plasma concentrations of apoLDL and LDL-cholesterol were positively correlated with synthetic rates of apoLDL (r = 0.74, P less than 0.001; r = 0.50, P less than 0.05, respectively). No correlation was noted between the fractional catabolic rate for apoLDL and apoLDL levels (or LDL-cholesterol). For further analysis, the patients were divided into three groups with stepwise increases in apoLDL concentrations. When apoLDL levels rose significantly, from 83 +/- 5 SEM to 122 +/- 2 to 149 +/- 5 mg/dl, synthetic rates for apoLDL also increased significantly from 11.6 +/- 12. to 17.0 +/- 0.9 to 23.8 +/- 1.8 mg/d/kg ideal weight. In contrast, the fractional catabolic rate of apoLDL was not different among the three groups (0.32 +/- 0.03 vs. 0.29 +/- 0.02 vs. 0.33 +/- 0.03/d). No relation was noted between synthesis of total body cholesterol (or bile acids) and concentrations, production rates, or removal of apoLDL. Thus, concentrations of apoLDL and LDL-cholesterol in these subjects with plasma cholesterol levels from low-normal to mildly elevated were regulated mainly by synthetic rates of apoLDL and not by LDL catabolism.     

Simvastatin in the treatment of hypercholesterolemia in elderly patients

Twenty elderly (mean age, 69 years), hypercholesterolemic patients (low-density lipoprotein [LDL] levels greater than or equal to 160 mg/dl) were supplied a lipid-lowering diet for one month and then received 10 mg of simvastatin daily for 12 months. Total cholesterol levels fell significantly, from 304.6 mg/dl at baseline to 277.4 mg/dl after one month on the diet, to 245.9 mg/dl after one month of simvastatin, and to 216.1 mg/dl after two months of simvastatin; total cholesterol levels remained significantly lower (221.6 mg/dl at month 12). LDL levels decreased significantly, from 217.6 mg/dl at baseline to 130.4 mg/dl at month 12. High-density lipoprotein levels increased significantly only at months 2 and 3. Apolipoprotein (apo) A levels increased significantly, from 147.2 mg/dl at baseline to 217.9 mg/dl at month 12. There were no significant changes in triglyceride or apo B levels. No changes in blood pressure, heart rate, or body weight or in results of laboratory tests were noted. Few side effects were reported. It is concluded that simvastatin is safe and effective in the treatment of hypercholesterolemia in elderly patients.     

Associations of Fas (CD95), tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), and biochemical manifestations in elderly persons

BACKGROUND: This study investigated the relationships of soluble Fas (CD95) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) vs. biochemical manifestations. METHODS: Serum concentrations of soluble Fas, TRAIL, and biochemical parameters were measured in 171 healthy adults. RESULTS: There were no significant age- and gender-related differences in Fas and TRAIL concentrations. However, aspartate and alanine aminotransferase and gamma-glutamyl transferase (AST, ALT, and GGT) activities were significantly higher in men with Fas > or =429.5 and TRAIL > or =63.2 pg/ml than in those with Fas <429.5 and TRAIL <63.2 pg/ml (26.8+/-10.9, 33.2+/-14.6, and 79.2+/-46.9 IU/l vs. 17.6+/-4.6, 20.4+/-7.8, and 35.3+/-21.3 IU/l, p<0.05, respectively). Serum triglyceride, total protein, and uric acid concentrations averaged 172.8+/-58.4 mg/dl, 7.8+/-0.3 g/dl, and 4.8+/-1.1 mg/dl in women with Fas > or =352.1 and TRAIL > or =64.9 pg/ml, which were significantly above the values of those with Fas <352.1 and TRAIL <64.9 pg/ml (116.9+/-49.2 mg/dl, 7.4+/-0.3 g/dl, and 3.7+/-0.7 mg/dl, p<0.05, respectively). Serum soluble Fas concentrations correlated significantly with AST (r=0.36, p<0.05), ALT (r=0.30, p<0.05), and GGT (r=0.29, p<0.05) in men and triglyceride (r=0.34, p<0.05), protein (r=0.27, p<0.05), and uric acid levels (r=0.41, p<0.05) in women. CONCLUSION: Apoptotic activity seems to have an important relationship to biochemical parameters, especially hepatic enzymes, total protein, triglyceride, and uric acid in elderly persons.     

Oat-derived beta-glucan significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with mild hypercholesterolemia

OBJECTIVE: To investigate the effect of bread formulated with 6 g of beta-glucan (oat soluble fiber) on serum lipids in overweight normotensive subjects with mild to moderate hypercholesterolemia. DESIGN: Thirty-eight male subjects [mean age 59.8 +/- 0.6 yr, mean body mass index (BMI) 28.3 +/- 0.6 kg/m(2)] who were eligible for the study ate an isocaloric diet for a 1-week period. They were then divided into 2 groups: group A (n = 19), who were maintained on American Heart Association (AHA) Step II diet, including whole wheat bread, and group B (n = 19), who were maintained on AHA Step II diet containing high levels of monounsaturated fatty acids plus bread containing 6 g of beta-glucan (Nutrim-OB) for 8 weeks. Plasma lipids and glucose were measured at baseline and after weeks 8 in all subjects. All subjects were advised to walk for 60 minutes every day. RESULTS: There was a significant increase (upward arrow 27.8%) in plasma high density lipoprotein (HDL) cholesterol in the beta-glucan group (group A) from 39.4 +/- 2.0 to 49.5 +/- 2.1 mg/dL (P < 0.001), but there was no change in group B. There was a significant reduction in total cholesterol in the 2 groups to approximately the same extent: group A, from 232.8 +/- 2.7 mg/dL to 202.7 +/- 6.7 mg/dL; P < 0.001; and group B, from 231.8 +/- 4.3 mg/dL to 194.2 +/- 4.3 mg dL; P < 0.001. Plasma low density lipoprotein (LDL) cholesterol also decreased significantly in the two groups: group A, from 160.3 +/- 2.8 mg/dL to 133.2 +/- 5.4 mg/dL; P < 0.001; group B, from 167.9 +/- 4.3 mg/dL to 120.9 +/- 4.3 mg/dL; P < 0.001; however, the beta-glucan fortified diet was significantly more effective (downward arrow 27.3% vs. downward arrow 16.8%; P < 0.04). There was a small and insignificant reduction in plasma very LDL (VLDL) cholesterol and triglycerides in the two groups. Similarly, non-HDL cholesterol levels were also decreased, with beta-glucan diet producing significantly higher effect (downward arrow 24.5% vs. downward arrow 16.1%; P < 0.04). The beta-glucan diet also produced higher reduction in total cholesterol/HDL cholesterol ratio (downward arrow 33.3% vs. downward arrow 8.4%; P < 0.003) and LDL cholesterol/HDL cholesterol ratio (downward arrow 42.1% vs. downward arrow 13.3%; P < 0.001) than the diet without beta-glucan. The beta-glucan diet also decreased fasting plasma glucose (P < 0.4), whereas the other diet had no effect. Interestingly, both diets reduced body weight and BMI significantly, with beta-glucan diet having a greater effect. CONCLUSIONS: Six grams of beta-glucan from oats added to the AHA Step II diet and moderate physical activity improved lipid profile and caused a decrease in weight and, thus, reduced the risk of cardiovascular events in overweight male individuals with mild to moderate hypercholesterolemia. The diet with added beta-glucan was well accepted and tolerated.