Effects of Denosumab and Alendronate on Bone Health and Vascular Function in Hemodialysis Patients: A Randomized, Controlled Trial.

Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.

Serum ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin and brachial-ankle pulse wave velocity: The Mikkabi cohort study.

BACKGROUND AND AIMS: Findings of observational studies suggest cardioprotective effects of antioxidant vitamins and carotenoids. However, recent meta-analyses failed to show the beneficial effects of supplemental intake of antioxidants on cardiovascular disease (CVD). We aimed to assess the association between CVD risk and ß-cryptoxanthin in Japan, where Satsuma mandarin, a major source of ß-cryptoxanthin, is widely consumed. METHODS AND RESULTS: This was part of the Mikkabi cohort study. Surveys were conducted at baseline, in 2003 and 2005, and on follow-up in 2006, 2009, and 2013. We examined brachial-ankle pulse wave velocity (baPWV) with a high cut-off value set at 18.3 m s(-1). Hazard ratios (HR) and 95% confidence intervals for high baPWV were estimated using a Cox proportional hazards model with adjustment for potential confounders. A total of 635 participants with baPWV of less than 18.3 m s(-1) at baseline were included in the analysis. During the follow-up period of 57,921 person-months, 99 subjects developed high baPWV. After multivariate adjustment, the HR for high baPWV in the highest tertile compared with the lowest tertile was significantly low for ß-cryptoxanthin, ß-carotene, and total carotenoids. Serum concentrations of ß-cryptoxanthin and ß-carotene were higher in people who ate Satsuma mandarin frequently. Compared with <1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV. CONCLUSION: This study indicated that ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin are candidate micronutrients for preventing arteriosclerosis development. Further longitudinal and interventional studies will be required to validate the effect on CVD.

[Assessment of the influence of the balneo-physiotherapeutic procedures on microcirculatory blood flow in patients with occlusive diseases of the great arteries].

Assessment of the influence of the balneo-physiotherapeutic procedures on microcirculatory blood flow in patients with occlusive diseases of the great arteries. A comprehensive program of rehabilitation treatment of patients with atherosclerosis of the arteries of the lower extremities, including over venous laser light, gradient magnetic field on the collar region and calf muscles, dry carbon dioxide baths alternating with baths with horse chestnut. The program is pathogenetically justified the use of its high-performance, regardless of the predominance of a clinical syndrome. This allows recommending it for widespread use in clinical practice, including sanatorium conditions. Some methods that are included in a comprehensive program, in accordance with the proposed algorithm can be used in patients with atherosclerosis of the arteries of the lower extremities with the predominance of individual symptom complex.

Omega-3 fatty acids do not improve endothelial function in virologically suppressed HIV-infected men: a randomized placebo-controlled trial.

Omega-3 fatty acids decrease cardiovascular disease (CVD) mortality possibly due to antiinflammatory effect. Inflammation and endothelial dysfunction likely play a role in the heightened CVD risk in HIV. Our goal was to evaluate the effect of omega-3 fatty acids primarily on endothelial function and inflammation in HIV-infected adults with moderate CVD risk on stable antiretroviral therapy. We conducted a 24-week, randomized, double-blind, placebo-controlled study to evaluate the effect of omega-3-acid ethyl esters 1 g twice a day. Flow-mediated dilation (FMD) of the brachial artery, lipoproteins and markers of inflammation, endothelial activation, coagulation, and insulin resistance were measured at entry and week 24. There were no within- or between-group differences in change in FMD over 24 weeks (mean change in FMD -0.13% vs. 1.5% for treatment vs. placebo; p=0.21). There were no between-group differences in changes in lipoprotein levels or biomarkers tested, except soluble tumor necrosis factor receptor-I, which favored omega-3-acid ethyl esters. Omega-3 fatty acids did not improve endothelial function or activation, coagulation, or insulin resistance in virologically suppressed, HIV-infected men with moderate CVD risk; however, inflammation tended to improve. This suggests that omega-3 fatty acids may not be potent enough to counteract the enhanced inflammation and endothelial dysfunction due to HIV and antiretrovirals.

Effects of Garcinia atroviridis on serum profiles and atherosclerotic lesions in the aorta of guinea pigs fed a high cholesterol diet.

INTRODUCTION: The fruit extract of Garcinia atroviridis (G. atroviridis) contains hydroxycitric acid and flavonoids, which have been reported to have a hypolipidaemic property. This extract with solvent methanol was used to investigate its effects on serum lipid profiles of guinea pigs fed a high cholesterol diet. METHODS: 24 male Dunkin Hartley guinea pigs were randomly divided into four groups. The first group served as controls and was fed with commercial rabbit chow. The second group was given only G. atroviridis by oral gavage (50 mg/body weight). The third group was fed a one percent cholesterol diet in food pellets in order to induce atherosclerosis. The fourth group was administered G. atroviridis with cholesterol. All the treatments were given daily for eight weeks, after which the animals were sacrificed, and the blood and aorta were taken for biochemical analysis and histological studies. RESULTS: The supplementation of G. atroviridis with a cholesterol diet decreased the level of lipid profile in the serum. Histological studies showed a reduction in fat deposition in the aorta of high cholesterol diet animals given G. atroviridis as compared to the high cholesterol diet group. CONCLUSION: This study has shown that dietary intake of G. atroviridis has a tendency to decrease lipid composition levels in the serum and reduce fat deposition in the aorta of high cholesterol diet animals.

Acute effects of acupuncture treatment with Baihui (GV20) on human arterial stiffness and wave reflection.

OBJECTIVES: Treatment by manual acupuncture needling affects the vascular wall tone, and hemodynamic parameters for arterial stiffness may be characterized by treatment at the traditional acupuncture point (acupoint) of Baihui (GV20). METHODS: The acute effects of acupuncture treatment on arterial stiffness and wave reflection were investigated and, simultaneously, an augmentation index (AI), as an index of wave reflection, was estimated. These parameters were measured in male volunteers using applanation tonometry during 20 minutes of acupuncture treatment and 40 minutes post-acupuncture. RESULTS: During treatment, diastolic blood pressure (BP), but not systolic BP, increased significantly. Heart rates (HR) initially tended to increase and then decrease. The AI from radial arteries increased significantly, while central aortic blood pressure (CBP) was unaffected. Post-acupuncture, the effects lasted for 30-40 minutes. The average BP and HR were +10.1+/-0.3% and -7.2+/-0.2%, respectively, and the CBPs were not altered, but the AI decreased markedly; this latter effect presumably resulted from the involvement of neurovascular modulators. CONCLUSIONS: These results indicated that acute treatment at Baihui enhanced arteriosclerotic parameters. In post-acupuncture, the AI profoundly decreased, presumably resulting from the involvement with neurovascular modulators.

Vascular effects of diet supplementation with plant sterols.

OBJECTIVES: The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE). BACKGROUND: Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known. METHODS: In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis. RESULTS: Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increased plant sterol but equal cholesterol plasma concentrations. The PSE supplementation impaired endothelium-dependent vasorelaxation and increased cerebral lesion size after middle cerebral artery occlusion. To test the effects of cholesterol-lowering by PSE, apolipoprotein E (ApoE)-/- mice were randomized to Western-type diet (WTD) with the addition of PSE or ezetimibe (EZE). Compared with WTD, both interventions reduced plaque sizes; however, WTD + PSE showed larger plaques compared with WTD + EZE (20.4 +/- 2.1% vs. 10.0 +/- 1.5%). Plant sterol plasma concentration strongly correlated with increased atherosclerotic lesion formation (r = 0.50). Furthermore, we examined plasma and aortic valve concentrations of plant sterol in 82 consecutive patients with aortic stenosis. Patients eating PSE-supplemented margarine (n = 10) showed increased plasma concentrations and 5-fold higher sterol concentrations in aortic valve tissue. CONCLUSIONS: Food supplementation with PSE impairs endothelial function, aggravates ischemic brain injury, effects atherogenesis in mice, and leads to increased tissue sterol concentrations in humans. Therefore, prospective studies are warranted that evaluate not only effects on cholesterol reduction, but also on clinical endpoints.

[Effects of panax notoginseng saponins on expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells injury induced by oxidized low-density lipoprotein].

OBJECTIVE: To study the protective effect of panax notoginseng saponins (PNS) on human umbilical vascular endothelial cells (HUVECs) injury induced by oxidized low-density lipoprotein (ox-LDL) for investigating the mechanism of PNS in treating arteriosclerosis obliterans (ASO). METHODS: Taking the cultured HUVECs as target cells, ox-LDL was used to establish a model of injured HUVEC and it was then intervened by PNS. The morphologic changes of HUVEC were observed under light microscope; activity of cells was determined by MTT method; the adhesive percentage between ox-LDL treated HUVEC and monocyte detennined by protein quantification and the protein expression of intercellular adhesion molecule-1 (ICAM-1) determined by flow cytometry. RESULTS: At the time points of HUVEC being treated with ox-LDL (100 mg/L) for 12 h and 24 h, significant injury of HUVEC was shown, its activity reduced, the adhesion rate with monocytes elevated, and the protein expression of ICAM-l in HUVEC increased significantly (P < 0.05, P < 0.01). PNS showed significant effect in reversing all the above changes, as compared with the control group (without PNS treaded), respective significant difference was shown in all the four indexes (P < 0.05, P < 0.01). CONCLUSION: PNS has a protective effect on endothelial cells injury induced by ox-LDL,which may be one of its mechanisms in treating ASO. The protective effect of PNS is probably by way of down-regulating the expression of ICAM-1 in endothelial cells and inhibiting the adherence of monocytes to endothelial cells.

Green tea polyphenols inhibit oxidized LDL-induced NF-KB activation in human umbilical vein endothelial cells.

AIM: To examine the anti-inflammatory effects of green tea polyphenols on oxLDL-mediated TNFalpha expression and NF-KB activation in the human umbilical vein endothelial cells (HUVECs). METHODS: We postulate that green tea polyphenols regulate TNF-alpha gene expression by modulating NF-KB activation through their inhibition effect on IKB Kinase (IKK) activity and as scavenger of free radicals. Pretreatment of green tea polyphenols reduced oxLDL-induced production of proinflammatory cytokine TNF-alpha and NF-KB activation in dose dependent manner (p < 0.05). Post hoc comparison test with Mann Whitney between various dosage of green tea polyphenols in inhibition of NF-KB activation showed significant result (p < 0.05). RESULTS: In TNF-alpha expression, there was also declined TNF-alpha productions (p 0.09; 0.2 vs 0.4mg/ml: ns). The effect of green tea polyphenols on TNF-alpha expression were determined by Mann-Whitney test. There is significant difference between the first dose (0.1mg/ml) vs 0.2mg/ml polyphenols (p=0.009); between 0.1 vs 0.4 mg/ml polyphenols (p=0.009). There was no difference when the dose was increased from 0.2 mg/ml to 0,4 mg/ml polyphenols (0.141). In this study, green tea polyphenols showed significant effects on the inhibition of TNF-alpha through NF-KB activation pathway in HUVECs with oxidized LDL. CONCLUSION: Green tea polyphenol can be used to prevent the development of atherosclerosis.

Chunghyul-dan (Qingxie-dan) improves arterial stiffness in patients with increased baPWV.

Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. Chunghyul-dan (CHD) has anti-hyperlipidemic activity, anti-inflammatory activity and anti-atherogenic effects. To determine its clinical effect on increased arterial stiffness, we examined whether CHD improves arterial stiffness in patients with increased brachial-ankle PWV (baPWV). Thirty-five subjects with increased baPWV (> 1400 cm/sec) were recruited and randomized to a treatment group (20 subjects) or a control group (15 subjects). The treatment group was administered CHD at a dose of 600 mg three times a day for 8 weeks, and the control group received no medication (observation only). baPWV was assessed using a pulse pressure analyzer at baseline and after 8 weeks. Blood pressure and serum lipid profile were monitored in the treatment group. Our results indicate that baPWV was lowered significantly in the treatment group after 8 weeks of medication (p < 0.05), but not in the control group. Moreover, there were no significant changes in blood pressure and serum lipids profile except triglyceride level suggesting that the effect is largely independent of CHD's lipid-lowering effect or a blood pressure change. In conclusion, CHD appears to improve arterial stiffness in patients with increased PWV.

Association between nutrient intake and peripheral artery disease: results from the InCHIANTI study.

BACKGROUND: Little is known about the relationship between dietary patterns and peripheral arterial disease (PAD). Our aim was to estimate the association between nutrient intake and diagnosis of PAD. METHODS AND RESULTS: We assessed the nutrient intake of 1251 home-dwelling subjects enrolled in the InCHIANTI study, mean age 68 years (S.D.: 15). We explored the relationship between nutrient intake, obtained through the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire, and PAD, defined as an ankle-brachial index (ABI)<0.90. After adjustment for potential confounders, we found a reduction of the risk of having an ABI<0.90 associated with vegetable lipid intake>or=34.4 g/day (OR: 0.39; 95% CI: 0.16-0.97), Vitamin E intake>or=7.726 mg/day (OR: 0.37; 95% CI 0.16-0.84) and higher serum HDL cholesterol concentration (OR: 0.76; 95% CI: 0.63-0.92 for 10mg/dl increase). Age (OR: 1.11; 95% CI 1.07-1.14 for 1 year increase), smoking (OR: 1.03; 95% CI: 1.01-1.04 for 10 packs/year increase) and pulse pressure (OR: 1.11; 95% CI: 1.03-1.19 for 5 mmHg increase) were associated with an increased risk of PAD. CONCLUSIONS: A higher intake of vegetable lipids, Vitamin E and higher concentrations of serum HDL cholesterol characterize subjects free from PAD. Prospective studies are needed to verify whether this dietary pattern and/or interventions aimed at increasing HDL cholesterol exert some protective effect against PAD.

Antioxidant status and lipid peroxidation end products in patients of type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVE: In Type 1 diabetes mellitus (DM), hyperglycemia is considered a primary cause of diabetic vascular complications and is associated with oxidative stress. The role of antioxidants, particularly alpha tocopherol, in Type 1 DM and its contribution in the development of vascular complications is not clear. Therefore, the present study aims to investigate the relationship between antioxidant status (alpha tocopherol) and lipid peroxidation end products (malondialdehyde; MDA) in the plasma of 20 Type 1 DM and 20 nondiabetic healthy control subjects. MATERIAL AND METHOD: Lipid levels in all subjects were analyzed spectrophotometrically by enzymatic reagent kits. Plasma MDA was assessed by spectrofluorometry, whereas plasma alpha tocopherol was estimated by high performance liquid chromatography in Type 1 DM as well as in the control subjects of matched sex and ages. The results of Type 1 DM were compared with a control group using unpaired Student's t-test. The correlations between fasting plasma glucose and other laboratory parameters were assessed by Pearson rank correlation coefficient. RESULTS: The plasma MDA concentration was significantly higher in Type 1 diabetic patients as compared to controls, (p < 0.01). A significantly reduced plasma antioxidant status of Type 1 DM patients was found only in alpha tocopherol / total lipid as compared to controls (p < 0.05). However, no significant difference was observed in plasma a tocopherol and a tocopherol / total cholesterol (p > 0.05) as compared to the control subjects. The positive correlation between MDA and FPG was demonstrated in Type 1 diabetic compared with normal subjects. CONCLUSION: We conclude that antioxidant supplementation may be necessary for treatment to reduce oxidative stress for diabetic complication protection in Type 1 DM.

Suppressive effects of cacao liquor polyphenols (CLP) on LDL oxidation and the development of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic rabbits.

We investigated the properties of cacao liquor polyphenols (CLP), which have an antioxidative effect on low-density lipoprotein (LDL) and an anti-atherosclerotic effect in the spontaneous familial hypercholesterolemic model, the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit. After 6 months of dietary administration of CLP at 1% (w/w) to the KHC rabbits, a higher total cholesterol concentration was observed in the treatment group compared to the control group. However, no other effects were noted in lipid profiles in plasma or lipoproteins. The plasma concentration of thiobarbituric acid reactive substances (TBARS), which is a lipid-peroxidation index, was significantly decreased 1 month after the start of CLP administration compared to that of the control group. The antioxidative effect of CLP on LDL was observed from 2 to 4 months of administration. The area of atherosclerotic lesions in the aorta in the CLP group (32.01+/-1.58%) was significantly smaller than that in the control group (47.05+/-3.29%), and the tissue cholesterol and TBARS concentrations were lower in the CLP group than in the control group. The anti-atherosclerotic effect of CLP was confirmed both rheologically and histopathologically. An in vitro study using KHC rabbit-derived LDL revealed that CLP significantly prolonged the lag time of LDL oxidation that was induced by a lipophilic azo-radical initiator, 2,2'-azobis(4-methoxy)-2,4-dimethylvaleronitrile (V-70), or Cu(2+) from a low concentration of 0.1 microg/mL. The antioxidative effect of CLP was superior to those of the well-known antioxidative substances, vitamin C, vitamin E and probucol. Therefore, CLP suppressed the generation of atherosclerosis, and its antioxidative effect appeared to have an important role in its anti-atherosclerotic activity.

Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed.

Hypercholesterolemia, low HDL-C and oxygen radicals have been implicated in the development of atherosclerosis. Lignan complex isolated from flaxseed contains secoisolariciresinol diglucoside (SDG), 3-hydroxy-3methylglutaric acid (HMGA) and cinnamic acids. SDG and cinnamic acids are antioxidants, and HMGA is a hypocholesterolemic agent. Antioxidants are known to reduce hypercholesterolemic atherosclerosis. The objectives of this study were to determine if lignan complex reduces (i) serum cholesterol, (ii) oxidative stress, and (iii) atherosclerosis in hypercholesterolemic rabbits. Rabbits were assigned to four groups: Group I, control; Group II, lignan complex control (lignan complex, 40 mg/kg body weight daily orally); Group III, 0.5% cholesterol; Group IV, 0.5% cholesterol diet+lignan complex, (40 mg/kg body weight daily orally). Blood samples were collected before (time 0) and after 1 and 2 months of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for measurement of atherosclerotic plaques, MDA and aortic tissue chemiluminescence (Aortic CL), a marker of antioxidant reserve. Rabbits in Group III developed atherosclerosis (50.84+/-6.23% of the intimal surface of the aorta was covered with atherosclerotic changes) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, MDA and aortic MDA and antioxidant reserve. Lignan complex reduced the development of atherosclerosis by 34.37% and this was associated with a decrease in serum TC by 20%, LDL-C by 14%, TC/HDL-C by 34%, serum MDA by 35% and aortic MDA by 58%. Serum HDL-C was elevated by 30% in hypercholesterolemic rabbits and by 25% in normocholesterolemic rabbits with lignan complex. Lignan complex did not affect the TC and LDL-C and serum MDA in the normocholesterolemic rabbits. However, it increased the aortic MDA in the normocholesterolemic rabbits. These results suggest that lignan complex isolated from flaxseed reduced the extent of hypercholesterolemic atherosclerosis and this effect was associated with marked decreases in oxidative stress, serum total cholesterol, LDL-C and risk ratio, and elevation of serum HDL-C. Lignan complex may, therefore, be beneficial in preventing atherosclerosis, and reducing risk factors for coronary artery disease and stroke.

Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study.

The present study was conducted to examine the effect of eicosapentaenoic acid supplements on pulse wave velocity (PWV) in patients with dyslipidemia as a prospective open-labeled study. Eicosapentaenoic acid supplements (1,800 mg/day) were prescribed to 40 patients, and diet therapy in consultation with a nutritionist was conducted in 44 patients as a control group. These interventions were continued for 12 months, and PWV and blood examinations were performed at the start and end of these interventions. PWV increased in the control group but not in the eicosapentaenoic acid group. After adjustment for age, gender, the initial PWV, and the changes in mean blood pressure during the study period, a general linear model univariate analysis post hoc comparison demonstrated that the change in PWV during the period of study was significantly larger in the control group (42 +/- 20 cm/s) than in the eicosapentaenoic acid group (-9 +/- 19 cm/s) (p<0.05). Thus, this preliminary study suggested that eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia. A further study with a larger number of subjects is proposed to confirm this beneficial effect of eicosapentaenoic acid supplements on arterial stiffness.

[Patients with hyperlipidemia: inappropriate nutritional intake]. / Sujets hyperlipidémiques, des apports nutritionnels inappropriés.

OBJECTIVE: Gather knowledge on nutritional supplementation in patients with hyperlipidemia. METHODS: In an observational study on patients with hyperlipidemia, nutritional intake was assessed using a 7-day dietary questionnaire, provided on the first visit to a lipid clinic. RESULTS: 291 patients (201 men and 90 women) were studied. Calorie intake and proportion of energetic nutrients revealed low carbohydrate intake, low intake of dietary fibres, and excessive lipid and saturated fatty acid intakes. Patients with isolated hypercholesterolemia had nutritional intake very similar to the daily allowances recommended in France. Men with type III hyperlipidemia had the highest calorie intake and those with type IV dyslipidemia had the highest alcohol intake. Triglycerides increased with total energy intake and with fat intake (%). Body mass index was inversely correlated to carbohydrate intake. The duration of dyslipidemia was related to low vitamin C and B9 intake. The existence of risk factors (type 2 diabetes, hypertension, smoking or inactivity) was associated with less well-balanced diet and low protective micronutrient status. In the case of atherosclerosis, vitamin B9, C, E and beta-carotene intake was insufficient. Interactions existed between nutrient intake with correlations between fibres, vitamin B9, C and beta-carotene, suggesting that nutritional education should favour foodstuffs that provide them simultaneously. CONCLUSION: Nutritional intake in patients with hyperlipidemia is often far from that recommended and does not greatly differ from that in large non-selected populations. It can be considered as inappropriate because of the metabolic and cardiovascular risks in these patients. Adapted nutritional management is crucial.

Mild hyperhomocysteinemia: risk factor or just risk predictor for cardiovascular diseases?

Elevated plasma levels of homocysteine (hyperhomocysteinemia) are increasingly recognized as a potential risk for atherothrombotic vascular diseases by numerous epidemiological and clinical studies. There are increasing experimental data that indicate mechanisms by which homocysteine may alter the vasculature in a way that predisposes to atherosclerotic vascular disease. A key event in the vascular pathobiology of hyperhomocysteinemia seems to involve the induction of endothelial dysfunction due to a reduction of the endogenous antiatherothrombotic molecular nitric oxide. Elevated homocysteine levels can be efficiently and safely reduced in most of hyperhomocysteinemic patients by supplementation of folic acid and cobalamin. This reduction is associated with an improvement in endothelial function and other surrogate markers of atherothrombosis, like carotid plaque area and the rate of abnormal stress electrocardiograms. Whether or not this translates into clinical benefits, is still under investigation. The first clinical study on homocysteine-lowering vitamin supplementation in patients that had undergone coronary intervention showed a benefitial effect on the rate on restenosis and the need for revascularization which translated into a reduction of major coronary events. In contrast, in three larger scaled secondary intervention trials in patients with stable coronary disease or post non-disabling stroke, vitamin supplementation had no effect on future vascular events although baseline homocysteine levels were significantly associated with a worse prognosis. Until the results of more clinical trials are available, the clinical relevant question whether or not homocysteine is just a risk predictor or a modifiable risk factor can not definitely be answered.

5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders.

There is evidence of an association between depression and anxiety and cardio- cerebro-vascular conditions, but the mechanisms of this association are unknown. Here we review a possible role for the 5-lipoxygenase (5-LOX) pathway. 5-LOX is an enzyme that, in association with 5-LOX-activating protein (FLAP), leads to the synthesis of leukotrienes from omega-6 arachidonic acid. Production of active leukotrienes can be reduced by dietary omega-3 fatty acids, which also are beneficial in cardiac and psychiatric (e.g., depression) pathologies. Human 5-LOX and FLAP gene polymorphisms are a risk factor in atherosclerosis and cardio-cerebro-vascular pathologies; an overactive 5-LOX pathway is found in these diseases. Studies with 5-LOX-deficient transgenic mice suggest that 5-LOX activity may contribute to anxiety- and depression-like behaviors. Future research should characterize the role of the 5-LOX pathway in comorbid cardio-cerebro-vascular and psychiatric disorders and in the therapeutic actions of dietary omega-3 fatty acids.