Laparoscopic sleeve gastrectomy modifies cholesterol synthesis but not cholesterol absorption.

BACKGROUND AND AIMS: Each bariatric surgery procedure impacts differently on cholesterol synthesis and absorption. Although a restrictive procedure, sleeve gastrectomy resolves diabetes mellitus and, like mixed-type procedures, induces early changes in gastrointestinal hormones. To our knowledge the present study is the first to assess the effects of sleeve gastrectomy on cholesterol synthesis and absorption. METHODS AND RESULTS: 42 consecutive subjects with obesity and sleeve gastrectomy candidates were included in the study together with a control group of 20 subjects without obesity. Before sleeve gastrectomy and 10 months afterwards, all subjects underwent a clinical examination, blood tests, ultrasound visceral fat area estimation and determination of plasma lathosterol, campesterol and sitosterol concentrations. After sleeve gastrectomy, significant decreases were observed in BMI, waist circumference, visceral and subcutaneous fat, blood pressure, triglycerides, insulin and glucose levels, lathosterol and HOMA-IR. HDL-C and apolipoprotein AI levels increased significantly. No significant differences emerged in LDL-C, apolipoprotein B levels or cholesterol absorption markers. Lathosterol levels correlated significantly with BMI, visceral fat area and HOMA-IR. Differences in cholesterol intake after surgery were not significantly associated with differences in lathosterol, campesterol and sitosterol concentrations. CONCLUSIONS: Sleeve gastrectomy reduced the markers of cholesterol synthesis but did not modify cholesterol absorption. Changes in cholesterol synthesis and absorption were independent of variations in cholesterol intake, suggesting a specific sleeve gastrectomy-related effect.

Increased Bone Resorption: A Possible Pathophysiological Link Between Hypovitaminosis D and Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Vitamin D deficiency has been associated with the prevalence and severity of peripheral arterial disease (PAD); nevertheless, data on bone turnover in patients with PAD is lacking. The present study investigates a possible relationship between the markers of bone turnover and the presence and severity of PAD. METHODS: The study examined 143 patients, with a mean ± SD age of 75.3 ± 8.5 years (range 50.0-93.0 years), of both sexes, admitted to a department of internal medicine. All patients underwent ankle brachial index (ABI) assessment by Doppler velocimetry. Serum levels of 25(OH) vitamin D and two markers of bone turnover, C-terminal telopeptide of type I collagen (sCTX) and bone isoenzyme of alkaline phosphatase, were measured. The differences between patients with normal ABI and patients with PAD were analyzed. Pearson and Spearman correlation coefficients were calculated and independent predictors were identified through a stepwise linear regression analysis. Odds ratios were calculated with a logistic regression model. RESULTS: Compared with patients with a normal ABI (≥0.90), patients with PAD (ABI < 0.90) presented with significantly lower levels of 25(OH) vitamin D (12.2 ± 9.6 ng/mL vs. 16.7 ± 8.7 ng/mL; p = .006) and a significantly higher concentration of sCTX (1.1 ± 0.7 ng/mL vs. 0.6 ± 0.4 ng/mL; p < .001). There was a positive correlation between ABI and serum concentration of 25 (OH) vitamin D (r = 0.3; p < .001), whereas ABI was inversely correlated with the concentration of sCTX (r = -0.358; p < .001). At logistic regression analysis, age, cigarette smoking, and both vitamin D and sCTX were independent predictors of an ABI < 0.90. CONCLUSION: These results support the hypothesis that hypovitaminosis D and increased bone turnover are risk factors for the presence and severity of PAD. Furthermore, the presence of PAD, even if asymptomatic and diagnosed by a reduced ABI, could identify a population at risk for osteoporosis and osteomalacia.

Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery.

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1ß, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1ß, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1ß showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1ß. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1ß, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1ß could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.

Non-cholesterol sterols in different forms of primary hyperlipemias.

BACKGROUND AND AIMS: We investigated the behaviour of non-cholesterol sterols, surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol), in primary hyperlipemias. METHODS AND RESULTS: We studied 53 patients with polygenic hypercholesterolemia (PH), 38 patients with familial combined hyperlipemia (FCH), and 19 age- and sex-matched healthy control subjects. In all participants, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled to mass spectrometry. To correct for the effect of plasma lipid levels, non-cholesterol sterol concentrations were adjusted for plasma cholesterol (10² µmol/mmol cholesterol). Patients with FCH were more frequently men, and had higher body mass index (BMI), fasting glucose, insulin and HOMA-IR. Lathosterol was higher in FCH than in pH or controls (p < 0.05). Campesterol was significantly lower in FCH (p < 0.05), while no differences were found between pH and controls. Sitosterol displayed higher values in pH compared to FCH (p < 0.001) and controls (p < 0.05). Spearman's rank correlations showed positive correlations of lathosterol with BMI, waist circumference, HOMA-IR, triglycerides, apoprotein B, and a negative one with HDL-cholesterol. Sitosterol had a negative correlation with BMI, waist circumference, HOMA-IR, triglycerides, and a positive one with HDL-cholesterol and apoprotein AI. Multivariate regression analyses showed that cholesterol absorption markers predicted higher HDL-cholesterol levels, while HOMA-IR was a negative predictor of sitosterol and BMI a positive predictor of lathosterol. CONCLUSIONS: Our findings suggest the occurrence of an increased cholesterol synthesis in FCH, and an increased cholesterol absorption in pH. Markers of cholesterol synthesis cluster with clinical and laboratory markers of obesity and insulin resistance.

Case report. Hyperlipoproteinaemia(a): which is the optimal therapy? A case report.

This case report presents the clinical history of a patient with elevated lipoprotein(a) and small size isoform, associated with mixed hyperlipaemia, which was probably familial combined hyperlipaemia. After premature myocardial infarction, the subject was treated with fibrates. Niacin was started after recurrence. One year ago, after another episode of acute coronary syndrome, rosuvastatin was added to niacin. The atherogenicity of this lipid disorder, along with the different options for therapy is discussed.

Lifestyle intervention improves microvascular reactivity and increases serum adiponectin in overweight hypertensive patients.

BACKGROUND AND AIMS: Obesity and hypoadiponectinemia are often associated with high blood pressure. Moreover, microvascular dysfunction is reported to be an early event in patients with hypertension and may be involved in the pathogenesis of organ damage. METHODS AND RESULTS: We investigated the impact of 8-week moderate-intensity aerobic training on adiponectin plasma levels and skin microvascular reactivity in 24 overweight sedentary patients (18 men, age 44+/-6 years, body mass index 28+/-3 kg/m(2)) with never-treated grade 1 essential hypertension. Twenty-four age- and sex-matched hypertensive patients, who were examined twice at 8-week intervals in the absence of exercise training, served as controls. Exercise training was followed by a significant reduction in waist circumference (from 97+/-9 to 95+/-9 cm, p<0.05) and an increase in adiponectin plasma levels (from 11.9+/-3 to 12.5+/-4 mg/L, p<0.05). An inverse correlation was found between adiponectin change and waist circumference change (r=-0.43, p<0.05). The area under the curve after post-occlusive reactive hyperemia at skin laser-Doppler examination increased significantly after aerobic training (from 876+/-539 to 1468+/-925 PU/s, p<0.001). A positive correlation was found between exercise-induced variations of post-occlusive reactive hyperemia and adiponectin plasma levels (r=0.41, p<0.05). Office or 24-h blood pressure values did not change significantly. CONCLUSION: In sedentary overweight patients with mild hypertension, moderate aerobic training improves cutaneous microvascular reactivity and adiponectin plasma levels. These changes precede blood pressure reduction and may serve as biomarkers of the efficacy of non-drug treatment in hypertensive patients.

Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study.

BACKGROUND AND AIMS: Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant beta-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved. METHODS AND RESULTS: The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6g of plant sterol-enriched FM (n=60) or control FM product (n=56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2+/-2.0 to 147.4+/-2.8 mg/dL (p=0.01). A significant reduction was observed for total cholesterol (from 263.5+/-2.6 to 231.0+/-3.2mg/dL, p=0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07+/-1.78 to 38.04+/-1.14 pg/ml, p=0.018) but not in patients taking the control product (from 42.56+/-2.12 to 43.19+/-2.0 pg/ml, p=NS). Campesterol and beta-sitosterol levels were not influenced by phytosterol consumption. CONCLUSIONS: Daily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.

Renal dysfunction predicts long-term mortality in patients with lower extremity arterial disease.

BACKGROUND: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. OBJECTIVES AND DESIGN: This prospective study investigated the relation between renal dysfunction and long-term all-cause and cardiovascular mortality in a population of nonsurgical patients with lower extremity arterial disease (LEAD). SUBJECTS AND METHODS: A total of 357 patients with symptomatic LEAD underwent baseline glomerular filtration rate (GFR) estimation by the 4-variable Modification Diet in Renal Diseases equation, and were then followed for 4.2 years (range: 1-17). RESULTS: During follow-up, 131 patients died (8.6 deaths per 100 patient-years), 79 of whom (60%) from cardiovascular causes. All-cause death rates were 3.8, 6.6, and 15.5 per 100 patient-years, respectively, in the groups with normal GFR, mild reduction in GFR (60-89 mL min(-1) per 1.73 m2) and chronic kidney disease (CKD; <60 mL min(-1) per 1.73 m2; P < 0.001 by log-rank test). Compared to patients with normal renal function, the risk of all-cause and cardiovascular death was significantly higher in patients with CKD [hazard ratio, respectively, 2.23, 95% confidence interval (CI): 1.16-4.34, P = 0.017; 2.15, 95% CI: 1.05-4.43, P = 0.03]. The association of CKD with all-cause and cardiovascular mortality were independent of age, LEAD severity, cardiovascular risk factors and treatment with angiotensin-converting enzyme (ACE)-inhibitors, hypolipidaemic and antiplatelet drugs. The power of GFR in predicting all-cause death was higher than that of ankle-brachial pressure index (P = 0.029) and Framingham risk score (P < 0.0001). CONCLUSION: Chronic kidney disease strongly predicts long-term mortality in patients with symptomatic LEAD irrespective of disease severity, cardiovascular risk factors and concomitant treatments.

Fat distribution and endothelial function in normal-overweight menopausal women.

BACKGROUND: Adipose tissue is not an inert deposit of fat; in the truncal area, it seems to be metabolically active, due to the adipokines produced locally. These substances are related to insulin resistance, inflammation and atherosclerotic damage to the vascular system. The development of ultrasound methodologies enable better estimation of fat distribution and more detailed investigation of the metabolic aspects of the fat depots and their impact on the initial stages of atherosclerosis. AIM OF THE STUDY: To investigate the influence of abdominal fat on endothelial function, the initial stages of atherosclerotic vascular damage and its relationship with inflammatory status in normal-overweight subjects [n. 162, body mass index (BMI) >25 kg/m(2) to <30 kg/m(2)]. METHODS: A total of 162 Caucasian postmenopausal women (mean age 54 +/- 4 years, menopausal age 8 +/- 4 years) were subdivided on the basis of the median value of the visceral fat distribution and associations with brachial flow-mediated vasoactivity (FMV), BMI, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), total and LDL cholesterol investigated. RESULTS: Subjects with lower levels of visceral fat had a higher brachial FMV (7.9 +/- 4.3 vs. 5.1 +/- 3.2%, P < 0.05) and lower BMI, waist, sICAM-1, sVCAM-1, total and LDL cholesterol. In univariate analyses, abdominal visceral fat showed a direct correlation with sICAM-1 (r = 0.43, P < 0.001), and an inverse correlation with FMV (r = -0.49, P < 0.01). Moreover an indirect relationship emerged between brachial FMV and sICAM-levels (r = -0.36, P < 0.05). In a multivariate analysis the predictive variables for brachial FMV were LDL cholesterol (beta = -0.22, P < 0.05), visceral fat (beta = -0.32, P < 0.05), sICAM-1 (beta = -0.18, P < 0.05), HDL cholesterol (beta = 0.25, P < 0.05) and brachial diameter (beta = -0.27, P < 0.05). Subcutaneous fat and triglycerides were also included in the model. CONCLUSIONS: In Caucasian normal-overweight women, visceral fat thickness was directly associated with the level of soluble ICAM-1 and inversely with FMV, thereby showing its relevance to endothelial function and the inflammatory state.

Natriuretic peptides levels are related to HDL-cholesterol with no influence on endothelium dependent vasodilatation.

BACKGROUND: The natriuretic peptides, Brain Natriuretic Peptide (BNP), C-type Natriuretic Peptide (CNP), are mediators of cardiovascular homeostasis. The impairment of arterial ability to vasodilate, also known as endothelial dysfunction, represents the first stage of atherosclerotic damage and may be assessed as brachial flow mediated vasodilation (FMV) in human. Generally an altered brachial FMV is documented in association to several cardiovascular risk factors as hypercholesterolemia. Aim of the study was to evaluate the behaviour of BNP and CNP in hyperlipemia and the potential relationship to FMV. PATIENTS AND METHODS: Forty-four hyperlipemic patients (LDL-cholesterol > 130 mg/dl and/or triglycerides > 150, age 35-60 y) of both genders and 20 normolipemic patients, matched for age and sex were investigated. RESULTS: Patients had lower values of brachial FMV in comparison to controls (3.9 +/- 3.5 vs 7.5 +/- 0.5%, p < 0.005), no differences were observed in BNP (4.6 +/- 4.6 vs 5.9 +/- 3.4 ng/mL, p = n.s) and CNP (4.1 +/- 5.8 vs 5.7 +/- 3.3 ng/mL, p = n.s). Univariate analysis showed a positive correlation between BNP and HDL-cholesterol values (r = 0.36, p = 0.001). In the multivariate analysis, LDL-cholesterol (beta = -0.57), HDL-cholesterol (beta = 0.26) and brachial artery diameter (beta = -0.33) were predictors of brachial FMV. The only predictive variable for CNP was HDL-cholesterol (beta = 0.37). CONCLUSIONS: The present study suggested that natriuretic peptides, BNP and CNP, are not altered in patients affected by hypercholesterolemia. Nevertheless, the levels of HDL-cholesterol are strictly related to the values of CNP. This observation, in humans, adds another mechanism to the vascular control exerted by HDL.

Low-grade systemic inflammation impairs arterial stiffness in newly diagnosed hypercholesterolaemia.

BACKGROUND: Excess of cardiovascular risk among patients with chronic inflammatory diseases has been attributed to increased arterial stiffness. Hypercholesterolaemia has been demonstrated to promote a low-grade inflammatory status. The objective of the present study was to define, in hypercholesterolaemia, the influence of plasma lipids, low-grade inflammation, and indices of adiposity on aortic pulse wave velocity, a measure of arterial stiffness and cardiovascular risk. MATERIALS AND METHODS: Anthropometric characteristics, plasma lipids, C-reactive protein and aortic pulse wave velocity were measured in 85 subjects (60 patients with newly diagnosed never-treated hypercholesterolaemia and 25 age- and sex-matched normocholesterolaemic controls). RESULTS: Plasma C-reactive protein and aortic pulse wave velocity were significantly higher among hypercholesterolaemic patients than in controls (P < 0.05 for both). Aortic pulse wave velocity was associated with age (r = 0.24, P = 0.04), body mass index (r = 0.33, P = 0.006), waist (r = 0.42, P < 0.001) and hip (r = 0.32, P = 0.007) circumferences, as well as with systolic (r = 0.34, P = 0.003) and diastolic (r = 0.30, P = 0.01) blood pressures, plasma C-reactive protein (r = 0.51, P < 0.001), total cholesterol (r = 0.45, P < 0.001), and low-density lipoprotein cholesterol (r = 0.46, P < 0.001). In the multivariate analysis, waist circumference and C-reactive protein levels predicted increased aortic stiffness, independently of traditional cardiovascular risk factors. The degree of independent association between cholesterol, systolic blood pressure and aortic stiffness increased when indices of adiposity and inflammation were excluded from the multivariate analysis. Comparable results were obtained when the analyses were restricted to hypercholesterolaemic patients. CONCLUSIONS: Low-grade systemic inflammation and abdominal fat, more than traditional risk factors, are major determinants of reduced arterial distensibility in hypercholesterolaemia.

Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity.

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. OBJECTIVE: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. METHODS: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age /=4 determinations multiplied by the disease duration (r = -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta = -0.28, p<0.05). CONCLUSIONS: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia.

BACKGROUND: Fasting and post-prandial hypertriglyceridemia have been associated with endothelial dysfunction. OBJECTIVE: To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load. METHODS: Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients. RESULTS: Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7 +/- 1 mmol/L at baseline vs. 4.2 +/- 1, 6.5 +/- 1, 6.6 +/- 2, and 5.3 +/- 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3 +/- 2% at baseline vs. 2.8 +/- 1, 2.2 +/- 1, and 1.3 +/- 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7 +/- 1.3 vs. 2.1 +/- 0.8 mmol/L), ICAM (480 +/- 113 vs. 269 +/- 65 ng/mL) and VCAM (1821 +/- 570 vs. 1104 +/- 376 ng/mL), and an increase in FMV (4.3 +/- 2 vs. 7.1 +/- 2%). Post-prandially triglycerides increased (2.1 +/- 1 at baseline vs. 2.4 +/- 2 and 3.6 +/- 1 mmol/L after 4 and 6 h), FMV decreased (7.1 +/- 2 at baseline vs. 5.8 +/- 2, 5.5 +/- 2, 5.9 +/- 2, 6.4 +/- 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = -0.34; P < 0.05) and ICAM (r = -0.66; P < 0.001). CONCLUSIONS: The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.

Association between endothelial dysfunction and major cardiovascular events in peripheral arterial disease.

BACKGROUND: Patients with peripheral arterial disease (PAD) are characterized by a high mortality for cardiovascular events. An impairment of endothelial function, expressed as brachial-artery flow-mediated vasodilation (FMV), has been described in PAD patients. Aim of this study was to investigate the association between FMV and cardiovascular events in patients with PAD. PATIENTS AND METHODS: Thirty-eight patients with intermittent claudication (71% men, mean age 71 years) were divided into two groups according to the presence or absence of previous major cardiovascular events (myocardial infarction or stroke). RESULTS: Brachial FMV was significantly lower in patients with a history of myocardial infarction or stroke (n = 16) than in patients without cardiovascular events (3.2 +/- 3.6% vs. 5.7 +/- 3.6%; p = 0.042). In the group with cardiovascular events there was a significantly higher proportion of subjects in the lower FMV tertile (56% vs. 18%), and a lower proportion of subjects in the upper tertile (25% vs. 41%; chi 2 test, p = 0.047). CONCLUSION: We conclude that FMV of the brachial artery is significantly reduced in PAD patients with a history of stroke and myocardial infarction. These cross-sectional results suggest a potential role of FMV as a marker of major cardiovascular events.

Postprandial endothelial impairment and reduced glutathione levels in postmenopausal women.

BACKGROUND/AIM: Postmenopausal age is characterized by a higher risk for coronary heart disease (CHD) and postprandial lipemia is strictly related with the evidence of CHD. The aim of the study was to clarify the vascular effects of postprandial state in postmenopausal women. METHODS: Ten postmenopausal women (mean age 57 +/- 8 years) without vascular risk factors and history of cardiovascular disease underwent an oral fat load test. Endothelial function, expressed as brachial flow-mediated vasodilation (FMV), lipid parameters and reduced glutathione (GSH) were evaluated at baseline and 2, 4 and 6 h after the load. RESULTS: FMV showed a significant decrease at the 2nd hour (2.3 +/- 2.6%, vs. baseline 7.7 +/- 2.8%, p < 0.05) and overlapping to the basal value after 4 h. Triglycerides increased postprandially at the 2nd and 4th hour (1.6 +/- 0.6 micromol/l, 1.8 +/- 0.5 micromol/l vs. baseline 0.9 +/- 0.4 micromol/l, p < 0.05), decreasing thereafter. GSH decreased at the 2nd hour of the postprandial phase (5.1 +/- 1.9 micromol/l vs. baseline 8.4 +/- 1.9 micromol/l, p < 0.05), normalizing successively. At the univariate analysis a negative correlation was found between FMV and triglyceride changes (r = -0.37, p < 0.05) and a positive one between FMV and GSH modifications (r = 0.40, p < 0.05). CONCLUSION: These data demonstrated that postprandial lipemia transiently impairs endothelial reactivity by an oxidative burden, partly dependent to triglyceride increase.

Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males.

BACKGROUND: Endothelial dysfunction is considered the earliest stage of atherosclerosis. Postprandial phase is associated with a transient impairment of endothelial function concomitantly with the triglyceride-rich lipoprotein increase. This phenomenon may be explained by the oxidative burden induced by triglyceride-rich lipoproteins, reducing nitric oxide bioavailability. OBJECTIVE: To investigate the effect of a diet enriched with L-arginine, the substrate for nitric oxide synthesis on endothelial function in healthy volunteers. METHODS: Endothelial function (expressed as flow-mediated vasodilation (FMV) of the brachial artery), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, LDL-size, Lp (a) and reduced glutathione (GSH) were evaluated in seven healthy males (mean age 23 +/- 3 years) without cardiovascular risk factors. Measurements were made at baseline and 2, 4 and 6 h after a standardized oral fat load. L-arginine (6 g daily) was administered for 10 days. On the 11th day the oral fat load and the parameters examined previously at entry were repeated. RESULTS: After the first oral fat load, FMV significantly decreased at 2 and 4 h, and overlapped with the basal levels at 6 h. After L-arginine treatment, FMV significantly decreased at 2 h and normalized after 4 and 6 h. Triglycerides increased at 2 and 4 h and decreased after 6 h in both sets of observations relating to before and after L-arginine administration. GSH dropped 2 h after the fat load, both before and after L-arginine. Before L-arginine, FMV exhibited a significant correlation with triglycerides (r= -0.426, P= 0.024) and GSH (r=0.48; P=0.009). After L-arginine, FMV was related to GSH (r=0.39; P=0.03) but not to triglycerides (r= -0.12; P=0.52). CONCLUSION: Postprandial endothelial impairment is partly abolished by L-arginine administration. These data, which require confirmation, suggest the importance of dietary choice for atherosclerosis prevention even in young healthy subjects.

Postprandial lipemia and associated metabolic disturbances in healthy and hyperlipemic postmenopausal women.

The increased risk for coronary artery disease observed in postmenopausal women is partly explained by a more atherogenic fasting lipoprotein profile. Moreover, natural menopause has been associated with an altered postprandial lipid profile. To better characterize the interaction between fasting and postprandial lipid profile after menopause, we examined postprandial changes in several lipid parameters in three age-matched groups of postmenopausal women (16 affected by mixed hyperlipemia, 17 by common hypercholesterolemia, and 17 normolipemic), who underwent a standardized oral fat-loading test. The magnitude of postprandial lipemia, expressed as 8-hour triglyceride incremental area under the curve, was greater in women with mixed hyperlipemia (1,326 +/- 372 mg x dL(-1) x h(-1)) than in normal (484 +/- 384 mg x dL(-1) x h(-1)) and hypercholesterolemic (473 +/- 223 mg x dL(-1) x h(-1); both P <.0001) women, and the differences held after adjustment for body mass index and fasting insulin. Women with mixed hyperlipemia showed a significant postprandial decrease in high-density lipoprotein 2 (HDL(2)) cholesterol, lipoprotein (a), and low-density lipoprotein (LDL) particle size. Both hypercholesterolemic and normolipemic women showed a significant postprandial decrease in HDL cholesterol and lipoprotein (a) levels but not in LDL size. In a multiple linear regression analysis, fasting triglyceride levels, insulin level, and waist-hip ratio were all independent predictors of the magnitude of postprandial lipemia. In conclusion, postmenopausal women with mixed hyperlipemia show a greater postprandial triglyceride increase and a more pronounced reduction in HDL cholesterol level and LDL size than hypercholesterolemic and normolipemic subjects. The presence of the features of insulin resistance syndrome could contribute to the deterioration of postprandial lipemic response in these subjects.