Influence of dietary intervention on microvascular endothelial function in coronary patients and atherothrombotic risk of recurrence.

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient's risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p < 0.001) and reactive hyperaemia area (4233.3 ± 127.73 vs. 9695.9 ± 205.23 arbitrary perfusion units per time, 129.04% increase, p < 0.001) improved after the dietary intervention in the cohort, without finding differences due to the diet (p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

Mediterranean Diet and Atherothrombosis Biomarkers: A Randomized Controlled Trial.

SCOPE: To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. METHODS AND RESULTS: In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n = 120) or nuts (MedDiet-Nuts; n = 119) versus a low-fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1-year differences in biomarkers. Differences are observed between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in high-density lipoproteins (HDLs) (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1 -antitrypsin levels (-6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments are associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake are linked to enhancements in biomarkers. CONCLUSION: MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.

The Mediterranean diet decreases prothrombotic microvesicle release in asymptomatic individuals at high cardiovascular risk.

BACKGROUND & AIMS: Circulating microvesicles (cMV) are small phospholipid-rich vesicles that contribute to the atherothrombotic process, and are biomarkers of cardiovascular disease (CVD) burden and progression. Diet is a cornerstone for CVD prevention, but dietary effects on cMV shedding are poorly characterized. We aimed at assessing the long term effects of a Mediterranean diet compared to a low-fat diet (LFD) on MV shedding by cells of the blood and vascular compartments in patients at high cardiovascular risk treated as per guidelines. METHODS: A total of 155 participants from the PREDIMED trial free of cardiovascular events after a mean follow-up of 5 years (n = 53 from the Mediterranean diet supplemented with extra-virgin olive oil -EVOO-; n = 49 from the Mediterranean diet supplemented with mixed nuts -Nuts-; and n = 53 from the LFD) were included in the study. At baseline and after one-year intervention, cMV were quantified and characterized by flow cytometry to identify their activated parental cell origin and prothrombotic potential by Annexin V (AV) binding. RESULTS: After one year of dietary intervention, platelet-derived PAC-1+/AV+ and CD62P+/AV+ cMV concentrations were lower in the Nuts group compared with the LFD and EVOO interventions (P = 0.036 and 0.003, respectively). In addition, prothrombotic cMV carrying tissue factor (CD142+/AV+) and CD11a+/AV+ cMV derived from activated cells, were significantly lower in both Mediterranean diet (EVOO and Nuts) interventions compared to one year of LFD (P < 0.0001 and 0.028, respectively). SMAα+/AV- cMV were lower in the LFD compared to the Nuts group after one year of intervention (P = 0.038). CONCLUSIONS: cMV are markers of cell activation and vascular injury that appear to be sensitive to dietary changes. Following a Mediterranean diet rich in EVOO or nuts is associated with lower cell activation towards a pro-atherothrombotic phenotype, suggesting a delay in the development of CV complications.

Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids.

Thrombosis is the most common underlying pathology responsible for morbidity and mortality in cardiovascular disease (CVD). Platelet adhesion, activation, and aggregation play central roles in hemostasis; however, the same process may also cause thrombosis and vessel occlusion at the site of ruptured atherosclerotic lesions leading to heart attack and stroke. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are an essential component of the platelet phospholipid membrane and play a major role in many aspects of platelet function. Dietary supplementation of ω-3 and ω-6 PUFAs has long been used to slow the progression of CVD and to prevent acute cardiovascular events. Despite this, the role of ω-3 and ω-6 PUFAs and their oxylipin metabolites in platelet function remains controversial due to the lack in our understanding of the mechanistic regulation controlling platelet reactivity in vitro and substantial evidence for PUFA regulation of thrombotic events in vivo. In this review, we will outline the role of platelet physiology in hemostasis and the effect of ω-3 and ω-6 PUFAs on platelet function, with special emphasis on in vivo effects on hemostasis and thrombosis due to the role of PUFAs and their bioactive lipids in circulation. Further, recent mechanistic insights and evidence for cardio-protective effects of PUFAs and their bioactive lipids will be discussed.

Complicaciones de la nutrición parenteral pediátrica / Complications of pediatric parenteral nutrition

No disponible

Amblyomin-X having a Kunitz-type homologous domain, is a noncompetitive inhibitor of FXa and induces anticoagulation in vitro and in vivo.

BACKGROUND: Cancer has long been associated with thrombosis and many of the standard chemotherapeutics used to treat cancer are pro-thrombotic. Thus, the identification of novel selective anticancer drugs that also have antithrombotic properties is of enormous significance. Amblyomin-X is an anticancer protein derived from the salivary glands of the Amblyomma cajennense tick. METHODS: In this work, we determined the inhibition profile of Amblyomin-X and its effect on activated partial thromboplastin time (aPTT) and prothrombin time (PT), using various approaches such as, kinetic analyses, amidolytic assays, SDS-PAGE, and mass spectrometry. RESULTS: Amblyomin-X inhibited factor Xa, prothrombinase and tenase activities. It was hydrolyzed by trypsin and plasmin. MS/MS data of tryptic hydrolysate of Amblyomin-X suggested the presence of Cys(8)-Cys(59) and Cys(19)-Cys(42) but not Cys(34)-Cys(55) disulfide bond. Instead of Cys(34)-Cys(55), two noncanonical Cys(34)-Cys(74) and Cys(55)-Cys(74) disulfide bonds were identified. Furthermore, when Amblyomin-X (1mg/kg) injected in rabbits, it prolonged aPTT and PT. CONCLUSION: Amblyomin-X is a noncompetitive inhibitor (Ki=3.9µM) of factor Xa. It is a substrate for plasmin and trypsin, but not for factor Xa and thrombin. The disulfide Cys(34)-Cys(55) bond probably scrambles with interchain seventh free cysteine residues (Cys(74)) of Amblyomin-X. The prolongation of PT and aPTT is reversible. GENERAL SIGNIFICANCE: In term of anticoagulant property, this is structural and functional characterization of Amblyomin-X. All together, these results and previous findings suggest that Amblyomin-X has a potential to become an anticancer drug with antithrombotic property.

US Findings in Patients at Risk for Pancreas Transplant Failure.

Purpose To determine if ultrasonographic (US) findings, including Doppler US findings, are associated with subsequent pancreas transplant failure. Materials and Methods A cohort of adult patients who underwent pancreas transplantation at a tertiary institution over the course of 10 years (from 2003 to 2012) was retrospectively evaluated for failure, which was defined as return to insulin therapy or surgical graft removal. The institutional review board provided a waiver of informed consent. All US images obtained within the 1st postoperative year were reviewed for three findings: arterial flow (presence or absence of intraparenchymal forward diastole flow), splenic vein thrombus, and edema. These findings were correlated with pancreas graft failure within 1-year after surgery by using Cox proportional hazards models and hazard ratios. Results A total of 228 transplants were included (mean patient age, 41.6 years; range, 19-57 years; 122 men, 106 women). Absent or reversed arterial diastolic flow was identified in nine of 20 failed transplants (sensitivity, 45%; 95% confidence interval [CI]: 23, 68) and in 15 of 208 transplants that survived (specificity, 93% [193 of 208]; 95% CI: 89, 96). The Cox proportional hazard ratio was 6.2 (95% CI: 3.1, 12.4). Splenic vein thrombus was identified in 10 of 20 failed transplants (sensitivity, 50%; 95% CI: 27, 73) and in 25 of 208 transplants that survived (specificity, 88% [183 of 208]; 95% CI: 83, 92). The Cox proportional hazard ratio was 4.2 (95% CI: 2.4, 7.4). Edema had the lowest specificity (Cox proportional hazard ratio, 2.0; 95% CI: 1.3, 2.9). In the multivariate analysis, only absent or reversed arterial diastolic flow remained significantly associated with transplant failure (adjusted hazard ratio, 3.6; 95% CI: 1.0, 12.8; P = .045). Conclusion Absent or reversed diastolic arterial Doppler flow has a stronger association with transplant failure than does splenic vein thrombus or edema. (©) RSNA, 2016.

Acetic acid in aged vinegar affects molecular targets for thrombus disease management.

To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.

The antithrombotic effects of carrot filtrates in rats and mice.

The prevention of arterial thrombotic disease has a high priority in developed countries. An inappropriate diet is known to enhance the risk for acute thrombotic events and a regular diet with proven antithrombotic effects might be a beneficial way to prevent disease. The present study was undertaken as a part of a series of investigations to examine vegetables and fruits for antithrombotic activity. A shear-induced in vitro platelet reactivity/thrombolysis method [Global Thrombosis Test, formerly Gorog Thrombosis Test] was used to screen 15 different varieties of carrot for antiplatelet and thrombolytic activities. Effective varieties were further investigated using an in vivo, laser-induced thrombosis model in mice. The different carrot varieties demonstrated a variable effect on thrombosis in vitro and in vivo. In particular, a variety designated SAKATA-0421 exerted an antithrombotic effect in vivo independent from heat treatment of the filtrate at 100 degrees C for 10 min. There was no significant correlation between antithrombotic activity and the levels of polyphenolics and any other biochemical parameter, including antioxidant activity, alpha-carotene and beta-carotene, alpha-tocopherol and ascorbic acid. Different varieties of carrot demonstrated a range of antithrombotic and prothrombotic activities. After oral intake, the particular heat resistant variety (SAKATA-0421) showed antithrombotic effect in vivo possibly due to antiplatelet reactivity and/or spontaneous thrombolytic activity. The present study added a new variety to the list of antithrombotic fruits and vegetables.

Olive oil and haemostasis: a review on its healthy effects.

UNLABELLED: Interest in the Mediterranean diet (MD) has grown worldwide. Despite the high complexity of its nutrients composition, olive oil emerges as its principal food, since it provides the higher percentage of energy and a lot of bioactive compounds. OBJECTIVE: In this review, we will discuss the benefits of diets enriched in virgin olive oil, whose effects are probably due not only to its oleic acid content but also to its other potentially health-promoting components. METHODS: Traditionally, the benefits of MD were linked to its effect on lipoprotein metabolism, but today we realise that there exists a whole sheaf of other benefits, including the components of haemostasis: platelet function, thrombogenesis and fibrinolysis. RESULTS: A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and thromboxane B2 plasma levels. Moreover, a particular interest has aroused about its capacity to decrease fasting factor VII plasma levels and to avoid or modulate its postprandial activation. In addition, tissue factor expression in mononuclear cells could be reduced with the chronic intake of virgin olive oil, and finally, studies performed in different experimental situation have shown that it could also increase fibrinolytic activity, reducing plasma concentration of plasma activator inhibitor type-1 (PAI-1). CONCLUSION: The MD is an alimentary model with a high content of monounsaturated fats that is capable of inducing a wide range of biological effects on the cardiovascular system. The application of modern focuses of study will dilucidate in the future the biological and clinical interest of these findings.

Dietary diacylglycerol extenuates arterial thrombosis in apoE and LDLR deficient mice.

INTRODUCTION: Prevention of arterial thrombotic diseases has high priority in developed countries. An appropriate diet is thought to be the best way to prevent or reduce the risk of mortality from such diseases. The aim of the present study was to evaluate the effect of diacylglycerol (DAG)-rich diets on arterial thrombosis. MATERIAL AND METHODS: Diet-sensitive congenital apolipoprotein E (ApoE) and LDL receptor (LDLR) double deficient mice were used. Thrombosis was assessed by the rate and extent of thrombus formation in the carotid artery of mice after laser irradiation. Plasma total cholesterol and triglyceride levels were measured by enzymatic assays. Four kinds of diets were used: high fat (Western-style) diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the TAG-rich and the DAG-rich high fat diet contained 20% TAG or DAG oil (w/w) with very similar fatty acid composition and 0.05% cholesterol ; Low fat (Japanese-style) diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 8 weeks from 6 weeks of age. RESULTS: Western-style high fat and TAG-rich high fat diets significantly increased thrombogenicity compared with low fat diet. DAG-rich high fat diet showed the lowest value, and the extent of thrombogenicity was equivalent to the low fat diet group. Fasting plasma total cholesterol level of DAG-rich high fat and low fat diet groups were significantly lower than that of TAG-rich high fat and high fat diet groups. Fasting plasma triglyceride levels in DAG-rich high fat diet group were significantly lower than in the TAG-rich high fat diet group. CONCLUSIONS: Dietary DAG but not TAG oil extenuates arterial thrombus formation. The mechanism of this effect is unclear and further investigated.

Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.

We have investigated the influence of dietary n-6/n-3 (ù-6/ù-3) polyunsaturated fatty acid-balance on the tendency to arterial thrombosis and the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Homozygous apoE-/- LDLR-/- double knockout mouse (DKO mice, 129XC57BL/6J background) and male C57BL/6 mice aged 6 weeks were divided into four groups. Each group was fed a diet containing a different n-6/n-3 ratio (Group l: 0.29; Group 2: 1.43; Group 3: 5.00; Group 4: 8), prepared with high linolenic (LNA) flaxseed oil (n-3 rich) and high linoleic (LA) safflower oil (n-6 rich). There were no statistical differences in the gain in body weight between the four groups. After 16 weeks, plasma triglyceride and LDL levels in Group 1 were significantly lower than in the other groups. Conversely, HDL was the highest. After 8 and 16 weeks, the tendency to arterial thrombosis was assessed using a He-Ne laser-induced thrombosis model. The degree of atherosclerosis was measured using the entire aorta method employing image analysis software. The n-6/n-3 ratio had a dose-dependent antithrombotic effect (thrombus volume decreased 23%, Group 1 vs. Group 4), In addition, the extent of atherosclerosis was less in the animals fed a low n-6/n-3 ratio compared with the high n-6/n-3 ratio group (atherosclerotic area decreased 40%, Group 1 vs. Group 4). The lowest n-6/n-3 ratio tested (0.29) was the most effective in suppressing the thrombotic and atherosclerotic parameters in these DKO mice.

An onion variety has natural antithrombotic effect as assessed by thrombosis/thrombolysis models in rodents.

INTRODUCTION: Prevention of arterial thrombotic diseases has a high priority in developed countries. As inappropriate diet has been shown to be an important risk factor for thrombotic events, regular antithrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test onion extracts for antithrombotic effect and to identify the effective varieties in Allium cepa. MATERIALS AND METHODS: A shear-induced platelet function test (haemostatometry) was used to screen for antithrombotic potential. Onion extracts showing significant antithrombotic activity in vitro were further assessed in vivo by using a laser-induced thrombosis test in mice. RESULTS AND CONCLUSIONS: An onion variety, Toyohira, showed significant antithrombotic activity both in vitro and in vivo. Toyohira showed thrombolytic activity in addition to the antiplatelet effect. Superkitamomiji, 2935A, and K83211 showed only thrombolytic activity. Quercetin, the richest flavonoid in onion, was measured, but no correlation was found between quercetin content and antithrombotic activity. It is concluded that onion A. cepa can be classified into varieties with or without antithrombotic and thrombolytic effects. This should be taken into account in future population studies on the antithrombotic effects of vegetables.

Sub-optimal taurine status may promote platelet hyperaggregability in vegetarians.

Although vegan diets typically have a very favorable effect on a range of vascular risk factors, several independent groups have reported that the platelets of vegetarians are more sensitive to pro-aggregatory agonists than are those of omnivores. In light of clear and convincing evidence that platelet function has an important impact on risk for thromboembolic events, it is important to clarify the basis of platelet hyperaggregability in vegetarians. A dietary deficit of long-chain omega-3 fatty acids is not likely to explain this phenomenon, since most omnivore diets do not include enough of these fats to discernibly influence platelet function. A more plausible possibility is that relatively poor taurine status--a function of the facts that plants are devoid of taurine and the human capacity for taurine synthesis is limited - is responsible. Plasma taurine levels are lower, and urinary taurine excretion is substantially lower, in vegetarians than in omnivores. Platelets are rich in taurine, which functions physiologically to dampen the calcium influx evoked by aggregating agonists--thereby down-regulating platelet aggregation. Supplemental intakes of taurine as low as 400 mg daily have been reported to markedly decrease the sensitivity of platelets to aggregating agonists ex vivo. Although the average daily intake of taurine from omnivore diets may be only about 150 mg, it is credible to speculate that a supplemental intake of this magnitude could normalize the platelet function of vegetarians in the long term; in any case, this thesis is readily testable clinically. Taurine is just one of a number of nutrients found almost solely in animal products--"carninutrients"--which are rational candidates for supplementation in vegans.

Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.

We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P<0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 +/- 0.03, 0.09 +/- 0.06 and 0.16 +/- 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall.

Mediterranean diet and health: is all the secret in olive oil?

OBJECTIVE: The purpose of this study was to review and analyze the synergies of olive oil related food consumption and nutrient intake in a Mediterranean region. DESIGN: Cross sectional study by face to face interview. SETTING: Population based random sample derived from the Catalan Nutrition Survey. SUBJECTS: 1600 individuals between 18 and 60 years of age. INTERVENTION: Two 24-hour recalls were administered to measure food and nutrient intakes. Food group consumption and nutrient intakes ratios between the highest(greater than 13.5% of total calories, 4th quartile)and lowest quartiles (less than 6.8% of total calories,1st quartile) of olive oil consumption were calculated. RESULTS: Comparing the highest quartile of olive oil consumption to the lowest, the highest ratios by food group consumption were observed for eggs, vegetables and fish in both men and women and non fried potatoes in women only. Lower ratios were associated in both sexes with soft drinks, commercially baked goods, processed meat and full fat milk and nuts in women only, and fried potatoes in men only. Analysis by nutrients showed higher ratios for carotenoids,monounsaturated fatty acids, vitamin E and folic acid in both sexes and Vitamin C and polyunsaturated fatty acids in women only. Lower ratios were seen for mono,di and polysaccharides, saturated fat, retinol and sodium in both genders and calcium niacin, thiamin,riboflavin and fibre in men only. CONCLUSION: Olive oil is a key contributor to the healthy aspects attributed to the Mediterranean diet, since its own health attributes may be added to those of foods that it's commonly served with (fish, vegetables), thus contributing to its thrombosis related disease preventive properties. As such, nutritional objectives in Mediterranean countries should address reducing saturated fats, without modifying quantities of olive oil,and increasing fish, vegetables and nuts.

The mediterranean lecture: wine and thrombosis--from epidemiology to physiology and back.

The protective effect of moderate alcohol consumption on the risk of cardiovascular disease has been consistently shown in many epidemiological studies. Antiatherogenic alterations in plasma lipoproteins, particularly increase in high-density lipoprotein (HDL) cholesterol,are considered as the most plausible mechanism of the protective effect of alcohol consumption on coronary artery disease (CHD). Other potential mechanisms contributing to the cardio-protective effects of moderate alcohol consumption include anti-thrombotic down regulation of blood platelet function, as well as of the coagulation and fibrinolysis balance. Since the proposal of a "French paradox" in the early Nineties, the possibility that consuming alcohol in the form of wine might confer a protection against CHD above that expected from its alcohol content, has made the topic"wine and health" increasingly popular. Many epidemiological studies have explored such a possibility, by comparing specific alcoholic beverage types (wine,beer, liqueur) in respect to their relative capacity to reduce the risk of CHD. In parallel, experimental studies have been done, in which wine and wine-derived products have been tested for their capacity to interfere with molecular and cellular mechanisms relevant to the pathogenesis of CHD. Wine might indeed conceivably have other ethanol unrelated beneficial effects. The biological rationale for such a hypothesis has been linked to the enrichment in grape-derived, non-alcoholic components, that possibly make it peculiar in respect to other alcoholic beverages. In fact, while the mechanisms underlying the effects of alcohol on cardiovascular disease have been limited to lipid metabolism and the haemostatic system, those related to wine consumption have also been extended to specific anti-inflammatory, antioxidant and nitric oxide related vaso-relaxant properties of its polyphenolic constituents. The effect of wine consumption has been carefully investigated to account for potential confounding of several conditions (inappropriate use of abstainers as control population, correlation between wine or total alcohol consumption and markers of healthy lifestyle and socioeconomic factors, diet, etc.). Strong evidence indicates that moderate wine consumption rather than confounders reduces both fatal and non fatal CHD events. In spite of the fact that the healthy effect of moderate intake of wine is by now well accepted, important issues remain to be resolved about the relationship between wine, alcohol and alcoholic beverages, the (possibly different) optimal amount of alcohol intake in men and women, the individual or environmental modulation of the alcohol related effect and the pattern of drinking. Some of these issues have been recently addressed in a large meta-analysis, in which the relationship between wine or beer consumption and CHD risk was quantitatively evaluated. We shall summarize here the experimental and epidemiological studies with wine or wine-derived products aimed at finding biological explanations for the supposed superior cardio-protective effects of wine consumption and to discuss some open questions about wine and vascular disease as approached in epidemiological studies.

Haemostatic cardiovascular risk factors: differential effects of red wine and diet on healthy young.

Two groups (21 healthy young male each) received either Mediterranean-type diet (MD) or high-fat diet(HFD) during 90 days. Between days 30-60, both diets were supplemented with 240 ml/day of red wine. MD alone was associated with: lower plasma fibrinogen (p=0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of protein S (p=0.013); longer BT (p=0.017); and marginal increases in platelet serotonin aggregation and secretion after stimulation with epinephrine. Red wine supplementation in both diets, resulted in lower plasma fibrinogen (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1 (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent, with a decrease in the HFD group and an increase in the MD group. No effects of diet or wine were detected in plasma proteins C and S, BT or VWF:Ag. Wine supplementation also resulted in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen (1 and 2 g/ml, p<=0.01).MD and moderate consumption of red wine have complementary,mostly beneficial effects on haemostatic CV risk factors. The longer BT in individuals on MD, independently of red wine, would denote less interaction of platelets with the vascular wall, which would be beneficial from the point of view of CV risk. However,the increased platelet aggregation/secretion after wine intake, possibly a "rebound" phenomenon, would be a risk factor for thrombosis.