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We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482 ± 61 ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2α, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids-(CGA; 334 mg/150 mL) and less caffeine (231 mg/150 ml) than MR had (210 and 244 mg/150 ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26 % in TAS, 13 and 13 % in CAT, 52 and 75 % in SOD, and 62 and 49 % in GPx after MLR and MR consumption (P < 0.001), respectively. ORAC increased after MLR (P = 0.004). No significant alteration in lipid peroxidation biomarkers was observed. Both coffees had antioxidant effects. Although MLR contained more CGA, there were similar antioxidant effects between the treatments. MRP may have contributed as an antioxidant. These effects may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction: The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking., Objective: To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE., Methods: Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids ( 14 C-Phospolipid, 3 H-Cholesteryl ester, 3 H-Triglyceride, and 14 C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants., Results: Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference ( p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0 mg/dL; p < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99 mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18 mg/dL; p < .05, 75.05 ± 22.52 vs 96.05 ± 25.63 mg/dL; p < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70 mg/dL; p < .05, 75.05 ± 22.52 vs 88.53 ± 20.24 mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups ( p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p = .066) were similar among groups., Conclusion: The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.

Dietary fats absorbed in the intestine are transported in the circulation as chylomicrons and remnants that have atherogenic potential. Although postprandial lipidemia is increased in older subjects, the specific chylomicron metabolism has not been explored in older subjects nor compared to young subjects, which is the focus of this study. After a 12 h fast, artificially-made emulsions similar to lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides were intravenously injected in 23 older (66±4 years) and 20 young (24±3 years) subjects. Sequential blood samples were collected to determine fractional clearance rates (FCR, in min -1 ) by compartmental analysis. Older subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl-ester FCR was lower in older subjects compared to the young (p=0.0001). The emulsion triglyceride FCR did not differ in the two groups. Tested in vitro , however, the lipolysis of the emulsion triglycerides was less intense in the older than in the young subjects. As delayed removal of remnants, indicated by the pronouncedly smaller cholesteryl ester FCR, is related to the presence of cardiovascular diseases, this can be a risk factor which could accelerate atherogenic complications occurring in aged subjects., Competing Interests: Conflicts of Interest The authors declare that they have no conflicts of interest.

This study aimed to explore lipoprotein metabolism in obstructive sleep apnea (OSA) and the effects of continuous positive airway pressure (CPAP). We studied 15 men with severe OSA [apnea-hypopnea index (AHI) ≥30 events/hour] and 12 age-, BMI-, and waist circumference-matched volunteers without OSA (AHI <5 events/hour). Carotid intima-media thickness (CIMT) was determined by a blind examiner. After 12 h fasting, a triglyceride-rich chylomicron-like emulsion, labeled with [ 14 C]cholesteryl oleate and [ 3 H]triolein, was injected intravenously followed by blood sample collection at preestablished times. Fractional clearance rate (FCR) of the radiolabeled lipids was estimated by compartmental analysis of radioisotope decay curves. Compared with controls, patients with OSA showed a significant delay in both cholesteryl ester FCR (0.0126 ± 0.0187 vs. 0.0015 ± 0.0025 min -1 ; P = 0.0313) and triglycerides FCR (0.0334 ± 0.0390 vs. 0.0051 ± 0.0074 min -1 ; P = 0.0001). CIMT was higher in the OSA group: 620 ± 17 vs. 725 ± 29 µm; P = 0.004. Cholesteryl ester FCRs were inversely related to total sleep time <90% ( r = -0.463; P = 0.029) and CIMT ( r = -0.601; P = 0.022). The triglyceride FCR was inversely correlated with AHI ( r = -0.537; P = 0.04). In a subgroup of patients treated with CPAP for 3 months (n = 7), triglyceride FCR increased 5-fold ( P = 0.025), but the cholesteryl ester FCR was unchanged. In conclusion, severe OSA decreased lipolysis of triglyceride-rich lipoproteins and delayed removal of remnants. CPAP treatment may be effective to restore the lipolysis rates., (Copyright © 2018 Drager et al.)

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with cardiovascular risk, but with normal plasma lipids., Objective: The aim was to investigate low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism in RA patients using radioactive nanoemulsions resembling an LDL lipid structure (LDE) as metabolic probes., Methods: Thirty patients with RA, 16 in remission and 14 in high activity, and 30 healthy controls were studied. LDE labeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-unesterified cholesterol ((3)H-UC) was intravenously injected followed by 24-hour plasma sampling. Fractional clearance rates (FCR, h(-1)) were calculated by compartmental analysis. Lipid transfers to HDL were assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified after chemical precipitation., Results: LDL cholesterol, triglycerides, unesterified cholesterol, and oxidized LDL were equal in RA and controls, and HDL cholesterol was even higher in RA. Compared with controls, apolipoprotein B was lower, apolipoprotein A1 was equal, and apolipoprotein E was higher in RA. Decay curves of LDE labels were faster in RA patients than in controls ((14)C-CE: 0.072 ± 0.066 and 0.038 ± 0.027, P = .0115; (3)H-UC: 0.066 ± 0.042 and 0.035 ± 0.039; P < .0044). FCRs were equal in 2 RA subgroups. Transfer of UC, triglycerides, and phospholipids to HDL was equal between RA and controls, but CE transfer was lower in RA. HDL size was smaller in RA patients than in controls (8.5 ± 0.5 nm; 9.2 ± 0.8 nm, P < .0001)., Conclusion: RA patients were more efficient in removing atherogenic LDL from plasma, as indicated by higher CE and UC FCR, with in lower apolipoprotein B. This was unexpected because of the higher cardiovascular risk in RA., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min(1)) of [(3)H]-TAG and [(14)C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) is considered the gold standard for myocardial viability. A pilot study was undertaken to compare FDG-PET using euglycemic hyperinsulinemic clamp before (18)F-fluorodeoxyglucose ((18)F-FDG) administration (PET-CLAMP) with a new proposed technique consisting of a 24-h low-carbohydrate diet before (18)F-FDG injection (PET-DIET), for the assessment of hypoperfused but viable myocardium (hibernating myocardium). Thirty patients with previous myocardial infarction were subjected to rest (99m)Tc-sestamibi-SPECT and two (18)F-FDG studies (PET-CLAMP and PET-DIET). Myocardial tracer uptake was visually scored using a 5-point scale in a 17-segment model. Hibernating myocardium was defined as normal or mildly reduced metabolism ((18)F-FDG uptake) in areas with reduced perfusion ((99m)Tc-sestamibi uptake) since (18)F-FDG uptake was higher than the degree of hypoperfusion-perfusion/metabolism mismatch indicating a larger flow defect. PET-DIET identified 79 segments and PET-CLAMP 71 as hibernating myocardium. Both methods agreed in 61 segments (agreement = 94.5 %, κ = 0.78). PET-DIET identified 230 segments and PET-CLAMP 238 as nonviable. None of the patients had hypoglycemia after DIET, while 20 % had it during CLAMP. PET-DIET compared with PET-CLAMP had a good correlation for the assessment of hibernating myocardium. To our knowledge, these data provide the first evidence of the possibility of myocardial viability assessment with this technique.

Background and Aims: Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein., Methods and Results: 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p < 0,05). Free-cholesterol, triglyceride and phospholipid transfer were equal, as well as HDL size., Conclusion: Remnant removal from circulation, estimated by cholesteryl oleate FCR was faster in vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effects of anabolic androgenic steroids (AAS) on chylomicron metabolism., Methods: An artificial lipid emulsion labeled with radioactive cholesteryl ester (CE) and triglycerides (TG) mimicking chylomicrons was intravenously injected into individuals who regularly weight trained and made regular use of AAS (WT+AAS group), normolipidemic sedentary individuals (SDT group) and individuals who also regularly weight trained but did not use AAS (WT group). Fractional clearance rates (FCR) were determined by compartmental analysis for emulsion plasma decay curves., Results: FCR-CE for the WT+AAS group was reduced (0.0073 ± 0.0079 min(-1), 0.0155 ± 0.0100 min(-1), 0.0149 ± 0.0160 min(-1), respectively; p<0.05), FCR-TG was similar for both the WT and SDT groups. HDL-C plasma concentrations were lower in the WT+AAS group when compared to the WT and SDT groups (22 ± 13; 41 ± 7; 38 ± 13 mg/dL, respectively; p<0.001). Hepatic triglyceride lipase activity was greater in the WT+AAS group when compared to the WT and SDT groups (7243 ± 1822; 3898 ± 1232; 2058 ± 749, respectively; p<0.001). However, no difference was observed for lipoprotein lipase activity., Conclusions: Data strongly suggest that AAS may reduce the removal from the plasma of chylomicron remnants, which are known atherogenic factors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effects of resistance training (RT) on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism., Methods: LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular RT for 1-4 years (age = 25 ± 5 years, VO(2)peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO(2)peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with (14)C-cholesteryl-ester and (3)H-free-cholesterol was injected intravenously, plasma samples were collected over 24-h to determine decay curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free-cholesterol, cholesteryl-ester, triacylglycerols and phospholipids. HDL size, paraoxonase-1 activity and oxidized LDL levels were also determined., Results: The two groups showed similar LDL and HDL-cholesterol and triacylglycerols, but oxidized LDL was lower in RT (30 ± 9 vs. 61 ± 19 U/L, p = 0.0005). In RT, the nanoemulsion (14)C-cholesteryl-ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs. 0.037 ± 0.028, p = 0.002), as well as (3)H-free-cholesterol (0.041 ± 0.025 vs. 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, RT (3)H-free-cholesterol was removed slower than (14)C-cholesteryl-ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups., Conclusions: RT accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in RT. RT also changed the balance of free and esterified cholesterol FCR's. However, RT had no effect on HDL metabolism related parameters., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events., Methods: Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with (14)C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24 h after injection to determine the fractional clearance rate (FCR, in h(-1)) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period., Results: In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443+/-0.0126; 0.0602+/-0.0187, p=0.0187 and 0.0503+/-0.0203; 0.0686+/-0.0216, p=0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation., Conclusion: In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood., Objective: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate., Methods: A low-density emulsion was labeled with [(14)C]-cholesterol ester and [(3)H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m(2)] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate., Results: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 +/- 0.044 in the obese group and 0.122 +/- 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h(-1)) was 0.052 +/- 0.021 in the obese subjects and 0.058 +/- 0.015 (p = 0.971) in the controls., Conclusion: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

The objective of this study was to evaluate the effects of exercise training on plasma removal of a cholesterol-rich nanoemulsion (LDE) that mimics low-density lipoprotein (LDL) lipid structure and binds to LDL receptors. LDE-derived cholesteryl ester plasma kinetics was studied in 24 exercise-trained and 20 sedentary male subjects. LDE labeled with [(14)C]cholesteryl ester was injected intravenously, and plasma samples were collected over a 24-h period to determine radioisotope decay curves. LDL cholesterol concentration was similar in both groups. Fractional clearance rate (FCR) of the nanoemulsion label was greater in the exercise-trained group compared with the sedentary group (0.138 +/- 0.152 and 0.0261 +/- 0.023 h(-1), respectively). A positive correlation was found (r = 0.60, P < 0.01) between FCR and peak O(2) consumption in trained subjects. Circulating oxidized LDL levels were lower in trained subjects compared with the sedentary group (9.0 +/- 2.0 and 16.0 +/- 3.0 mU/l). LDE was also injected into control and LDL receptor gene knockout mice submitted and not submitted to training. Muscle LDE uptake percentage was increased in the trained mice compared with the untrained mice (1.1 +/- 0.8 and 0.2 +/- 0.1, respectively, P < 0.0001) in the control group but not in the knockout animals, indicating that the LDL receptor is involved in the increased uptake elicited by exercise. These results show that exercise training increases LDE plasma removal, which in turn suggests that it also increases LDL receptors or LDL receptor activity.

A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with (3)H-cholesterol and (14)C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis.

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 +/- 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 +/- 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and (3)H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with (3)H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 +/- 0.017 vs 0.039 +/- 0.019 min-1; P < 0.05), but the FCR of 14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with (14)C-cholesteryl ester ((14)C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of (14)C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of (14)C-CE was observed in CDP compared to NO THERAPY (0.076 +/- 0.037 versus 0.046 +/- 0.021 h(-1); P < 0.05) and to CONTROL (0.0516 +/- 0.0125 h(-1); P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 +/- 16 and 88 +/- 16 mg/dl) compared to NO THERAPY (174 +/- 15 and 108 +/- 17 mg/dl; P < 0.05) and to CONTROL (200 +/- 24 and 118 +/- 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of (14)C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels.

Background: Development of coronary graft disease is currently the main cause of late heart-transplantation (HT) failure. HT patients frequently show hypercholesterolemia as well as alterations in chylomicron metabolism. These postHT changes may be important in coronary graft disease development. To clarify whether hypercholesterolemia is caused by decreased low-density lipoprotein (LDL) removal from the plasma, we studied the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptor., Methods: We studied 13 HT patients and 13 healthy normolipidemic subjects paired for sex, age, and body mass index. An emulsion labeled with C-cholesteryl oleate was injected intravenously, and blood samples were collected in predetermined intervals (5 minutes, 1, 2, 4, 6, and 8 hours) to determine the radioactivity decay curves and to calculate the fractional clearance rates (FCR)., Results: The plasma level of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, and apo B were greater in HT group than in the control group (P<0.005). FCR C-cholesteryl oleate was smaller in HT patients when compared with the control group (P=0.02)., Conclusion: The results showed that HT patients have a deficiency in the mechanisms of LDL removal from the plasma, as tested by the cholesterol-rich emulsion, and this may be important in the development of coronary graft disease.

The atherogenic role of a delayed intravascular catabolism of chylomicrons has been suggested by univariate analysis of case-control studies. However, it is not established whether this association is caused by a direct atherogenic effect of these lipoproteins or results from the presence of concurrent and metabolically-related coronary artery disease (CAD) risk factors. In this study, the plasma kinetics of a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate (CE) and 3H-triolein (TG) was determined in 93 subjects with or without angiographically-defined CAD. As compared with controls and even after adjustment for body mass index (BMI), LDL- and HDL-cholesterol, and the presence of traditional risk factors, CAD patients had 45% smaller fractional clearance rate (FCR) of TG, 41% smaller FCR-CE and 19% smaller dilapidation index (DI; P < 0.05). Among CAD patients, those with highest angiographic score had 66% smaller FCR-TG (P = 0.007), 50% smaller FCR-CE (P = 0.01) and 27% smaller DI (P = 0.004). In a multivariate logistic regression analysis, FCR-CE (P < 0.0001) and DI (P = 0.001) were the only independent predictors for the presence of CAD. In conclusion, we presently show that the rate of lipolysis and removal from the circulation of chylomicron-like emulsions constitutes an independent predictor of CAD and a marker of CAD severity.

Objectives: We sought to verify whether the intravascular metabolism of chylomicron-like emulsion may predict the clinical evolution of patients with coronary artery disease (CAD) undergoing secondary prevention therapy of CAD., Background: Case-control studies have suggested an association between impaired intravascular catabolism of triglyceride (TG)-rich lipoproteins and CAD. However, evidence is lacking with respect to the potential clinical relevance of this metabolic disorder in CAD patients., Methods: During a period of 4.5 +/- 0.9 years, we followed up 63 stable CAD patients (mean age 60 +/- 10 years) undergoing secondary prevention therapy (low-density lipoprotein cholesterol <100 mg/dl) in whom kinetic studies of the in vivo catabolism of chylomicron-like emulsions were performed. At enrollment into the study, fasting patients were injected intravenously with a chylomicron-like emulsion labeled with radioactive triglyceride (3H-TG) and cholesteryl esters (14C-CE) to evaluate the efficacy of intravascular TG lipolysis., Results: At baseline, CAD patients displayed a diminished fractional clearance rate (FCR) for 3H-TG (-26%; p = 0.027), for 14C-CE (-37%; p = 0.015), and for delipidation index (DI) (-26%; p = 0.02) as compared with 35 control subjects. During follow-up of secondary prevention therapy, 33% of CAD patients (n = 21) presented with clinically refractory angina and aggravated coronary angiographic severity. The FCR for 3H-TG (-44%; p = 0.005) and DI (-41%; p = 0.006) in those patients with refractory angina was significantly lower than that observed in those with stable evolution. Moreover, in a Cox multivariate regression analysis, the presence of a DI less than the median value was an independent predictor of an unfavorable clinical evolution (adjusted hazard ratio 3.32; 95% confidence interval 1.21 to 9.14; p = 0.020)., Conclusions: The current study establishes that delayed intravascular TG lipolysis is a strong and independent predictor of evolution to severe angina among patients undergoing secondary prevention therapy of CAD.

Slow chylomicron intravascular catabolism has been associated with coronary artery disease and screening for drugs that can speed-up this process can be important. In this study, the effects of etofibrate upon chylomicron metabolism was tested by determination of the plasma kinetics of a chylomicron-like emulsion model in 12 patients with coronary artery disease, aged 59+/-11 years, (total cholesterol: 240+/-41 mg/dl; triglycerides: 188+/-42 mg/dl) submitted to a randomized, crossover, double-blind, placebo-controlled study with administration of 1 g per day etofibrate or placebo for 1-month. A 1-month washout period was inserted between the treatment periods. Patients were intravenously injected a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate and 3H-triolein at baseline and after treatments. After etofibrate treatment, there was decrease of total cholesterol and triglyceride plasma levels and a trend to increase high-density lipoprotein cholesterol plasma levels. Etofibrate elicited 62% enhancement of post-heparin lipolytic activity and 100% increase of 3H-triglyceride fractional clearance rate compared with placebo treatment. 14C-cholesterol ester fractional clearance rate was 260% greater after etofibrate than after placebo. Therefore, a potent effect of etofibrate on both chylomicron lipolysis and remnant removal was achieved, indicating that this drug can be used to improve this metabolism in future prospective studies.

Objective: To verify the in vivo status of chylomicron metabolism in systemic lupus erythematosus (SLE) since there is a high incidence of atherosclerosis in this disease and chylomicrons may have an important role in atherogenesis., Methods: A chylomicron-like emulsion labeled with 14C-cholesteryl esters and 3H-triglycerides was injected intravenously into 10 female patients with inactive SLE and 10 healthy age- and sex-matched control subjects to determine the plasma kinetics of the emulsion lipids from consecutive plasma samples taken at regular intervals for 1 hour. Lipolytic activity was determined in vitro after incubation of the labeled emulsion with postheparin plasma., Results: The decay curves for the emulsion were markedly slowed in SLE. Chylomicron lipolysis, indicated by the fractional clearance rate (FCR) of emulsion 3H-triglyceride, was 2-fold smaller in SLE patients than in controls (mean +/- SD 0.023 +/- 0.011 versus 0.047 +/-0.015 minute(-1); P = 0.010). Chylomicron removal, indicated by emulsion 14C-cholesteryl ester FCR, was 3-fold smaller in SLE patients than in controls (0.007 +/-0.007 versus 0.023 +/- 0.011 minute(-1); P = 0.009). In vitro lipolysis in SLE patients was nearly half that of the controls (mean +/- SD 10,199 +/- 2,959 versus 6,598 +/-2,215; P = 0.014). Higher levels of very-low-density lipoprotein cholesterol and triglycerides and lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I were also observed in the SLE patients., Conclusion: SLE patients have disturbances in chylomicron metabolism that are characterized by decreased lipolysis and chylomicron remnant removal from the plasma. This finding, together with other alterations in lipid profiles that were confirmed in the present study, is largely accountable for the accelerated atherosclerotic process of the disease.

Background: Development of coronary graft disease is the most important cause of late heart graft failure. Alterations in plasma lipid profile are frequent in heart transplant (HT) patients, but they seem not to be prominent. Currently, the metabolism of chylomicrons, the lipoproteins that carry dietary lipids absorbed by the intestine, was evaluated because chylomicron remnants are considered atherogenic., Methods: An emulsion labeled with 3H-triolein and 14C-cholesteryl oleate and known to mimic the metabolic behavior of chylomicrons was injected intravenously after a 12-hr fast into 34 HT patients, 24 patients with end-stage heart failure (ESHF), and 30 healthy normolipidemic subjects. The plasma disappearance curves of the radioisotopes were determined from blood samples collected over 1 hr. In some of the patients and in controls, in vitro postheparin lipolytic activity was measured and an oral fat load test with postprandial measurement of triglyceridemia was performed., Results: Fractional clearance rate (in m(-1), median [25%; 75%]) of both emulsion 3H-triolein and 14C-cholesteryl oleate was extremely diminished in HT patients (HT: 0.0114 [0.0114; 0.0179] and 0.2x10(-8) [0.2x10(-8); 0.0041, respectively]; ESHF: 0.0226 [0.0223; 0.0568] and 0.0160 [0.0055; 0.0189]; control subjects: 0.0270 [0.0226; 0.0392] and 0.0090 [0.0042; 0.0180], respectively, P<0.05). HT patients also had reduced postheparin lipolysis and marked elevation of postprandial triglyceridemia compared with the controls., Conclusions: HT patients develop accumulation in the plasma of chylomicrons and their remnants. The observed alterations were so intense that they may suggest an important involvement of atherogenic chylomicron remnants in coronary graft disease.

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P < 0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P < 0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P < 0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.

Chylomicron catabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. In rats, triglyceride-rich emulsions can mimic chylomicron metabolism. To further validate this model in man, the emulsion was injected intravenously into fasting and into subjects previously fed a test fatty meal. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined. The fractional clearance rate (FCR) of both labels was markedly reduced in the fed subjects (triglycerides: fed = 0.018 +/- 0.007; fasting = 0.105 +/- 0.013 min-1, P < 0.001; cholesteryl ester: fed = 0.016 +/- 0.001; fasting = 0.040 +/- 0.006 min-1; P < 0.05) indicating that the emulsion and chylomicrons generated from the testinal lipid absorption compete for the same catabolic processes, confirming the validity of the method. The emulsion was injected into 11 patients with CAD and into 11 controls. All had plasma cholesterol < 240 and triglycerides < 250 mg/dl. FCR of triglycerides was 5-fold smaller in CAD compared to controls (0.028 +/- 0.004 and 0.141 +/- 0.069 min-1, respectively, P < 0.01). FCR of cholesteryl ester was 4-fold smaller in CAD than in controls (0.015 +/- 0.004 and 0.056 +/- 0.067 min-1 respectively, P < 0.05). These results indicate that both chylomicron lipolysis and remnant removal are diminished in CAD.

Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein resembling low-density lipoprotein (LDL) but with an additional apoprotein (apo), apo(a). To determine whether plasma Lp(a) levels can influence the clinical presentation and extent of coronary artery disease (CAD), Lp(a), plasma lipids and apolipoproteins were determined in 203 Caucasian subjects with CAD and in 66 subjects without CAD, all confirmed by cinecoronariography. CAD patients were divided into groups according to their clinical history. The extent of the disease was evaluated by a scoring system. Lp(a) was elevated in CAD patients compared to subjects without CAD. However, there was no difference between patients that had myocardial infarction as the first manifestation of the disease and those who had only angina pectoris for at least two years. Plasma Lp(a) levels were correlated with extent of the disease. Among patients with CAD, Lp(a) was higher in females. Lp(a) was also studied separately in 29 Black subjects, 12 without CAD and 17 with CAD. In Black subjects, Lp(a) was higher than in Caucasians but there was no difference between subjects with and without CAD. Among the other risk factors studied, only plasma apo B levels and smoking were correlated with CAD.

Objective: To determine lipoprotein(a) [Lp(a)] levels in systemic lupus erythematosus (SLE) and its possible correlation with thrombosis, disease activity, anticardiolipin antibodies (aCL) and steroid therapy., Methods: Serum Lp(a) levels were determined by radioimmunoassay (RIA) in 34 Caucasian patients with SLE and compared to 66 healthy subjects., Results: In patients with SLE Lp(a) levels were higher than in controls (42 +/- 35 vs 26 +/- 25 mg/dl, p = 0.01). Lp(a) levels were high (> or = 30 mg/dl) in 56% of the patients with SLE and in 30% of controls (p = 0.02) but were not correlated with the clinical and laboratory findings., Conclusions: Lp(a) levels are significantly higher in patients with SLE and are not influenced by disease activity, thrombosis, aCL and steroid therapy.

Purpose: To evaluate the plasma concentration of lipoprotein (a) (Lp(a) in subjects with normal or altered coronary angiography, as a risk factor of atherosclerosis in a Brazilian population., Patients and Method: Lp(a) plasma levels were determined by radioimmunoassay in 31 subjects with normal angiography and in 131 subjects with atherosclerosis. Plasma cholesterol, triglycerides, apolipoprotein A, A1 and B were also determined as well as risk factors like systemic arterial hypertension, smoking habit, diabetes and physical activity., Results: Subjects with coronary disease had Lp(a) plasma levels of 41.9 mg/dl, compared to 23.9 mg/dl found in the normal group. Coronary artery disease risk was increased 2.3 times in those with plasma Lp(a) levels equal or above 25 mg/dl, compared to those with levels below this boundary. As to other known risk factors, only smoking habit has shown correlation with coronary artery disease., Conclusion: We confirmed the value of Lp(a) as a risk factor of coronary heart disease.