Determinants of High Parathyroid Hormone Levels in Patients With Severe Obesity and Their Relationship With the Cardiometabolic Risk Factors, Before and After a Laparoscopic Sleeve Gastrectomy Intervention.

BACKGROUND: Obesity is a risk factor for vitamin D deficiency and hyperparathyroidism. Hyperparathyroidism could exert a negative effect on glucose metabolism and vascular function. The aim of this study was to identify the determinants of hyperparathyroidism beyond vitamin D deficiency, whether hyperparathyroidism could have a negative impact on individual health and whether laparoscopic sleeve gastrectomy (LSG) negatively affects the levels of intact parathyroid hormone (iPTH) and 25(OH) vitamin D (25(OH)D). METHODS: We evaluated the levels of iPTH, 25(OH)D, and leptin, together with markers of insulin sensitivity and early cardiovascular disease, in a cohort of 160 patients with severe obesity before and after an LSG intervention. RESULTS: Ninety-seven percent of subjects had vitamin D deficiency, and 72% of them had hyperparathyroidism. After correcting for possible confounders, we found a correlation between iPTH levels and carotid intima-media thickness, as well as with the HOMA index. After the LSG, 25(OH)D levels were significantly increased, while iPTH levels were significantly reduced. The reduction of iPTH was significantly correlated with the reduction of BMI, diastolic blood pressure, and leptin, which was the independent predictor of iPTH reduction. CONCLUSIONS: Our results suggest that vitamin D deficiency is not the sole determinant of hyperparathyroidism in severe obesity because visceral fat deposition and leptin could both play a role. Obesity-related hyperparathyroidism is associated with insulin resistance and atherosclerosis, although the results from previous studies were conflicting. Finally, LSG intervention does not negatively affect vitamin D status and improves hyperparathyroidism.

Operators' radiation exposure reduction during cardiac catheterization using a removable shield.

Cardiac catheterization through radial access is associated with significant ionizing radiation exposure for the operator. We aimed at evaluating whether a removable shield placed upon the patient could impact favorably on annual radiation exposure for the operator. We designed a pre-post study comparing radiation exposure in a total of five operators under standard protection procedures (first period) and after applying a removable shield (second period). Each period included all the procedures performed in 1 year. Radiation exposure was measured through three dosimeters on each operator. A total of 1610 procedures were performed during the first period, and 1670 during the second period. For each operator, Fluoroscopy Time (FT) per exam did not differ between the two periods (13.1 ± 1 vs 12.9 ± 2 min/exam, p = 0.73), whereas Dose-Area Product (DAP) per procedure was slightly higher in the second period (5.247 ± 651 vs 6.374 ± 967 mGy/cm2, p < 0.01). The use of a removable shield significantly reduced operators' radiation dose at the left bracelet (64.3 ± 13.3 µSv/exam vs 23.8 ± 6.0 µSv/exam, p = 0.003). This remained significant even after adjustment for DAP per procedure (p = 0.015) and number of operators participating to each procedure (p = 0.013), whereas no significant difference was observed for card (5.6 ± 10.5 µSv/exam vs 0.9 ± 0.3 µSv/exam, p = 0.36) and neck bands (3.3 ± 4.5 µSv/exam vs 2.0 ± 2.0 µSv/exam, p = 0.36) dosimeters. The use of a removable shield during cardiac catheterization reduces radiation exposure at the level of the operator's upper limb, whereas no difference was found for other body parts. This may help in reducing radiation exposure of operator's hand. DAP increase merits further investigation.

High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy.

BACKGROUND & AIMS: Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females. METHODS AND RESULTS: In 110 morbidly obese patients undergoing laparoscopic sleeve gastrectomy, hs-CRP as well as anthropometric assessment of adiposity, completed by electric bioimpedance and ultrasonography quantification of visceral fat area (VFA), were measured before and one year after surgery. As compared to males, obese female showed less severe overweight and prevalent subcutaneous fat deposition, but higher circulating hs-CRP. In obese females, hs-CRP was associated with VFA at baseline, independently of body mass index (BMI) and visceral adiposity index (OR 1.022 [95% CI 1.001-1.044]; p = 0.039). Based on decreases and increases in hs-CRP levels after surgery, two distinct subgroups of females were identified. Post-surgery decreases in hs-CRP was predominantly observed in patients with higher baseline levels of hs-CRP and associated with greater reduction of weight, BMI, fat and lean mass, VFA and visceral to subcutaneous fat ratio. Finally, we observed that high baseline values of hs-CRP were able to predict VFA reduction one-year after surgery, independently of BMI and visceral adiposity index (VAI) loss (OR 1.031 [95% CI 1.009-1.053]; p = 0.005). CONCLUSION: In obese females, hs-CRP levels might be a promising biomarker of visceral fat amount and dysfunction, in addition to predict the effectiveness of bariatric surgery in terms of loss of VFA one-year after surgery.

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.

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.

Endothelial dysfunction in vivo is related to monocyte resistin mRNA expression.

BACKGROUND: Resistin could be the linkage between the adipose tissue and the insulin resistance. In humans, the role of resistin on metabolic and vascular homeostasis is not well defined. The aim of this study was to investigate the possible association between resistin expression and insulin resistance. METHODS AND RESULTS: We evaluated the relationship between monocyte expression of mRNA and anthropometric and metabolic parameters of insulin resistance. We focused on the potential role of resistin on endothelial function. Thirty-nine patients with metabolic syndrome (MS) and clinically free from cardiovascular disease, and 15 healthy subjects were included in this study. All subjects underwent clinical examination, assessment of haematochemical parameters, bioimpedentiometry, measurement of monocyte resistin mRNA and of brachial-artery flow-mediated vasodilation (FMV). Patients with MS showed higher levels of interleukin-6 (IL; 2.1 +/- 1.2 vs. 1.2 +/- 0.9 pg/mL, P < 0.05) and reduced FMV (5.4 +/- 3.9 vs. 8.3 +/- 3.1%, P < 0.05). The subjects were divided into two groups: (i) subjects with high expression mRNA resistin levels and (ii) subjects with low or not detectable; Group 1 was younger (50 +/- 13 vs. 59 +/- 11 years, P = 0.01), showed higher IL-6 values (2.3 +/- 1.2 vs. 1.6 +/- 1.2, P = 0.03) and lower values of FMV (4.3 +/- 2.8 vs. 7.4 +/- 3.9%, P = 0.003). With univariate analysis monocyte mRNA showed a significant positive correlation with waist circumference (r = 0.27, P < 0.05) and IL-6 (r = 0.26, P < 0.05) and a negative correlation with FMV (r = -0.38, P < 0.005). With multivariate regression analysis brachial-artery diameter, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, IL-6 and RNAm resistin expression were independent predictors of reduced FMV. CONCLUSIONS: mRNA resistin negatively influences FMV, and is a possible in vivo index of endothelial dysfunction.

Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies.

Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis.

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.

[Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity]. / Aterosclerosi subclinica in giovani pazienti con artrite reumatoide e bassa attività di malattia.

BACKGROUND: There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA) are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. OBJECTIVES: To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. METHODS: Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score < or =3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. RESULTS: Patients had higher intima-media thickness than controls of all the sites evaluated at carotid artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. CONCLUSIONS: Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

Prognostic impact of low-shear whole blood viscosity in hypertensive men.

BACKGROUND: The role of blood viscosity as a marker for discriminating cardiovascular risk in essential hypertension remains uncertain. The aim of this study was to assess whether whole blood viscosity (WBV) could be useful in assessing cardiovascular risk in men with a first diagnosis of hypertension. DESIGN: A total of 331 middle-aged men with newly diagnosed essential hypertension (age at entry 40-64 years, average blood pressure 151/95 mmHg) underwent low-shear-rate (0.94 s(-1)) and high-shear-rate (94.5 s(-1)) WBV determination and were then followed for a mean of 4.8 +/- 3 years (range 0-12 years). RESULTS: Cardiovascular event rates in the bottom, middle and top tertiles of the distribution of low-shear WBV were 1.10, 2.13 and 4.43 per 100 patient-years, respectively (log-rank test, P < 0.001). After taking into account several established cardiovascular risk factors in a Cox survival analysis, a raised low-shear WBV conferred an increased risk for cardiovascular events (top vs. bottom tertile hazard ratio = 3.42, 95% confidence interval = 1.4-8.4, P = 0.006; middle vs. bottom tertile hazard ratio = 2.25, 95% confidence interval = 0.9-5.6, P = 0.09). The independent association between high-shear-rate WBV and cardiovascular events bordered statistical significance (P = 0.07). Inclusion in the survival model of low-shear-rate resulted in a significantly greater chi(2) improvement (P < 0.05) than inclusion of high-shear-rate WBV. CONCLUSIONS: In hypertensive men, an increased WBV at low shear rate is a predictor of cardiovascular events independently from the effect of several traditional risk factors. Low-shear WBV is a better discriminator of cardiovascular risk than high-shear WBV.

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.

Left ventricular mass and systolic dysfunction in essential hypertension.

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.