International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Carotid plaque morphology and cerebrovascular events.

AIM: Beside the degree of stenosis, plaque morphology obtained by the B mode ultrasound technique has been considered to define the plaque at risk for cerebrovascular events, and a subset of patients who deserve more strict surveillance. Our aim was to evaluate the relationship between plaque morphology, progression of stenosis, and the development of new cerebrovascular events. METHODS: We followed up by carotid duplex scan 230 asymptomatic patients, evaluating the degree and progression of internal carotid (ICA) stenoses and plaque morphology of the atherosclerotic lesions. RESULTS: During the follow-up period (median 32 month, range 6-125 months) 7% of patients developed ischemic neurological events of which 1.7% was a stroke. Of these events, only 5.7% correlated with carotid lesions. The new neurological events correlated with the degree and progression of stenoses, with a non homogeneous echographic appearance and irregular surface. The progression of the degree of stenoses was the parameter that correlated the most with the development of new neurologic symptoms. Nevertheless, the lesions that progressed modified their echographic pattern from homogeneous to non homogeneous in 78% of cases. Irregular surface and high degree of stenoses more than the baseline echographic pattern seem to correlate with plaque progression. CONCLUSION: Our follow-up study confirmed that ICA stenosis is a benign condition: very few strokes clearly correlated to the stenosis were observed. Nevertheless, the major predictors of risk for cerebrovascular events, besides the degree of stenoses, are the progression of the degree of stenosis, irregular surface and non-homogeneous echographic appearance.

Premature arterial and venous events in three families. Effect of folate levels and MTHFR mutation mediated by family/generation and homocysteine levels.

Plasma homocysteine levels result from the effect of genetic and environmental factors. We investigated the hypothesis of familial association between folates, methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia with acute events, studying three families through pedigree analysis and log-linear graphical models. In 43 subjects, 13 had homocysteine levels of >15 micromol/l. In Family A, premature venous and arterial events occurred in father and son, respectively. In Family B, several arterial premature events occurred and very high homocysteine level was found in a healthy 18-year-old nephew. In Family C, stroke occurred at the age of 16 in a boy. In all three families, all subjects with premature cardiovascular events had high homocysteine level as well as MTHFR mutation, either homozygous or heterozygous. The present results underline that hyperhomocysteinemia has a direct conditional association with cardiovascular events. Moreover, homocysteine level is a variable that links the indirect association of folates, MTHFR mutation and cardiovascular event.

Evidence of postprandial absorption of olive oil phenols in humans.

BACKGROUND AND AIM: Olive oil phenols are potent antioxidants in vitro. If this were to be also demonstrated in vivo, it would help to explain the beneficial effects of this typical ingredient of the Mediterranean diet. This study was designed to determine the presence in lipoprotein fractions of two phenolic compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and whether their absorption induces an antioxidant effect in vivo. METHODS AND RESULTS: Two trials were performed. In the first (Long-term), 14 healthy volunteers followed two diets, each for one month. The only difference between the diets was that the first supplied 50 g of extra virgin olive oil per day, where-as the second one supplied 50 g of refined olive oil with no simple phenols, as demonstrated by GC-MS analysis. There were no changes in LDL oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and plasma from fasting samples drawn at the end of each diet period. In the second study (Postprandial), eight healthy volunteers received an oral fat load consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30', 60', 120', 240', 360', and major plasma lipoprotein classes were separated. The concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered in all lipoprotein fractions, except VLDL, with concentrations peaking between 60' and 120'. However, a very high variability in tyrosol and OH-tyrosol absorption was observed among subjects. Vitamin E content of LDL and HDL did not vary significantly throughout the study. Plasma antioxidant capacity increased significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p = 0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox). CONCLUSIONS: These findings suggest that phenolic compounds in olive oil are absorbed from the intestine, though not through a pathway dependent on chylomicron formation, and may exert a significant antioxidant effect in vivo, probably in the postprandial phase.

Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia.

Photodynamic therapy (PDT) appears to be a novel promising modality to prevent intimal hyperplasia (IH) and restenosis after angioplasty. Local PDT, that consists of local delivery of photosensitizing agents followed by intraluminal local irradiation, represents a recent advancement. This methodology requires optimization in order to achieve the best prompt outcome especially in terms of pharmacokinetics of the photosensitizing agent. We studied the pharmacokinetic properties by using the photosensitizing agent Zn(II)-phthalocyanine (ZnPc), locally released by a channeled balloon. The efficacy of local PDT in reducing IH was evaluated in an experimental rabbit model of arterial injury. The maximum accumulation of ZnPc was found at 30 min: the injured portion of the artery gave a ZnPc recovery of 1.18 micromol/mg, as compared with undetectable amounts of ZnPc in the non injured arteries; within 90 min after the local delivery, clearance of the agent was almost complete. Local PDT produced an effective reduction of IH in our vascular injury model: at 7, 14, 21 and 28 days IH and intima/media ratio (IMR) was significantly reduced as compared with balloon injured arteries. The local delivery of ZnPc showed favourable pharmacokinetic properties, that allow the performance of PDT immediately after the vascular injury. Local PDT performed in these conditions represents a promising approach to prevent IH after balloon injury. Further studies are needed to better clarify the biological response of the injured arterial wall to local PDT.

[Extrahospital cardiac arrest: the experience of Mestre Emergency Service]. / Arresto cardiaco extraospedaliero: l'esperienza di Mestre Emergenza.

BACKGROUND: Out-of-hospital cardiac arrest (AC) is one of the leading causes of death in industrialized countries. AC-related mortality can be reduced by rapid intervention. We report the experience of the emergency medical service (EMS) of Mestre on the management of out-of-hospital AC. METHODS: We analyzed 80 cases of out-of-hospital AC observed consecutively by the EMS of Mestre from February 1996 to September 1997: 72 cases (90.0%) involved cardiac etiology and 8 (10.0%) non-cardiac etiology. The 72 cases involving cardiac etiology were divided in three groups: group A) 12 unwitnessed ACs (16.7%); group B) 12 ACs witnessed by EMS personnel (16.7%); group C) 48 bystander-witnessed ACs (66.6%). RESULTS: In group A, in which 4/12 patients (33.3%) presented ventricular fibrillation (FV) or pulseless ventricular tachycardia (TV) as initial rhythm, return of spontaneous circulation (ROSC) was obtained in one patient with FV and in one patient with asystole. In group B, 7/12 patients (58.3%) presented FV or TV as initial rhythm; in this subgroup, ROSC was obtained in 71.4% of cases (4 cases with FV and one case with TV) and discharge in 42.9%, while in the subgroup with other rhythms the rate of ROSC was 40.0% (two patients with pulseless electrical activity later died). In group C, 35/48 patients (72.9%) presented VF or TV as initial rhythm; in this subgroup, ROSC was achieved in 42.9% of cases (13 cases with FV and 2 cases with TV) and discharge in 14.3%, while in the subgroup of bystander-witnessed AC with other rhythms the rate of ROSC was extremely low (7.7%) (one patient with asystole later discharged). In group C, bystander cardiopulmonary resuscitation (CPR) was performed in 20/48 patients (40.1%). In these patients, FV or TV were more frequently recorded as initial rhythm (80.0 vs 67.9%; p < 0.05). In patients without bystander CPR, the interval between the time of collapse and the time of the first defibrillation was shorter in the patients who were admitted than in patients who died (6.0 +/- 1.4 vs 10.9 +/- 4.4 min; p < 0.05). Considering all patients with FV or TV as initial rhythm and the interval between the collapse and the first defibrillation exactly recorded, the percentage of ROSC decreased when the interval between the collapse and the first defibrillation increased. CONCLUSIONS: Our data confirm that early defibrillation is the key factor in the prognosis of out-of-hospital AC. The data suggest that the immediate delivery of bystander CPR could extend the interval in which defibrillation is effective.

Percutaneous excimer laser angioplasty of lower limb vessels: results of a prospective 24-month follow-up.

The aim of this prospective study was to assess the effectiveness and the long-term patency effect of excimer laser angioplasty in peripheral arterial obstructive disease. Seventy-eight patients referred for excimer laser angioplasty of lower limbs have been followed up for up to 24 months. Ankle/brachial systolic pressure index, color Doppler mapping, and arterial digital subtraction angiography were performed. Immediate procedural success was achieved in a high percentage of patients (97%). Balloon angioplasty was also used in 85% of patients. Early reocclusions occurred in 8% of patients. The cumulative patency rate was 47% at the 12-month interval and 40% at the 24-month interval. Poor runoff and the length of the lesions negatively influenced the outcome. Excimer laser angioplasty is an effective procedure, indicated in selected patients showing < 10 cm occlusions and good runoff.

[Prevalence of clinically silent pulmonary embolism in deep venous thrombosis of the legs]. / Prevalenza di embolia polmonare clinicamente silente nella trombosi venosa profonda degli arti inferiori.

BACKGROUND: Thromboembolic venous disease is a possible lethal condition which is very often present in clinical practice. The aim of this study was to evaluate the prevalence of clinically occult pulmonary embolism (PE) in a group of patients with recent proximal deep venous thrombosis (DVT), and the relationship between prevalence of PE and DVT extension, echographic features of the thrombi, anticoagulant therapy administered. MATERIALS AND METHODS: The study enrolled 93 patients with DVT of the proximal lower extremities, without clinical symptoms and signs of PE. All patients were submitted to echo color-Doppler and ventilation-perfusion lung scan. The results were analysed by a score system for the echographic scan and by a series of probability criteria, as recommended by the PIOPED investigators, for the lung scan. RESULTS: All patients were recognised to suffer from proximal DVT. High probability lung scans for PE were found in 43 subjects (46.2%), intermediate probability in 14 (15%), low probability in 7 (7.7%), very low-normal in 29 (31.1%). The prevalence of PE failed to show any significant difference with respect to DVT extension, ultrasonographic features of the thrombi and anticoagulant therapy administered. CONCLUSIONS: The results obtained show a high prevalence of asymptomatic PE in patients with DVT, and suggest the need of an extensive use of lung scan in this kind of patients, and the utility of an early detection of DVT, in order to establish an intense antithrombotic therapy, irrespective of the extension of the thrombus with US.

The characteristics of the thrombi of the lower limbs, as detected by ultrasonic scanning, do not predict pulmonary embolism.

OBJECTIVE: To evaluate whether pulmonary embolism (PE), as detected by perfusion lung scan, could be predicted by the ultrasonic (US) characteristics of the thrombi in patients with deep venous thrombosis (DVT) of the lower limbs. PATIENTS: Ninety-three consecutive patients with DVT and no symptoms of lung involvement (52 men, 41 women; mean age, 67 +/- 17 years). MEASUREMENTS AND RESULTS: The degree of thrombotic involvement of the lower limbs was assessed using a US score system ranging from 1 (indicating a subsegmental, nonocclusive thrombus) to 16 (massive, occlusive). According to the echographic and color-Doppler features, the thrombi were classified in terms of echoreflectivity, adhesiveness to the vein wall, and organization. The diagnosis of PE (PIOPED criteria) was highly probable in 46% of the patients, intermediate in 15%, low in 8%, and very low/normal in 31%. No correlations were found between the lung scan findings on one side and the venous scoring system or the US features of the thrombi on the other side. CONCLUSIONS: While confirming that the prevalence of PE in patients with DVT is elevated, we failed to define a subgroup of patients at higher risk. Our data imply that lung scan should be used extensively for the detection of silent PE and that anticoagulation should not be graded on US findings.

[The prevalence of carotid and coronary diseases in asymptomatic patients at high risk for atherosclerosis]. / Prevalenza di carotidopatia e coronaropatia in pazienti asintomatici ad elevato rischio per aterosclerosi.

To evaluate the prevalence of carotid lesions and silent coronary artery disease in asymptomatic patients, we studied 31 subjects with one or more risk factors for atherosclerosis. All patients have been studied by means of non invasive cardiologic evaluations and carotid echo color Doppler. The prevalence of carotid and or coronary artery disease was 80%. The prevalence of silent coronary artery disease was 19% and carotid artery disease 61%. Patients with more than one risk factor showed a higher prevalence of carotid lesions (84%) than those with only one risk factor (16%). In conclusion, the prevalence of carotid disease in asymptomatic patients, at risk for atherosclerosis, is high. The echo color Doppler system represents the best approach to study carotid atherosclerosis in vivo. When carotid lesions are present, a non invasive cardiological evaluation may be useful to reveal a silent coronary artery disease.

n-3 fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects.

Recent data suggest that treatment with n-3 fatty acids could enhance the susceptibility of plasma low-density-lipoprotein (LDL) to oxidation. Twelve hypertriacylglycerolemic, hemodialyzed patients were treated with 2.5 g n-3 fatty acids/d for 2 mo. Treatment was then withdrawn for 2 mo (washout phase). Plasma total cholesterol and LDL cholesterol increased significantly (9% and 28%) and plasma triacylglycerols decreased significantly after the n-3 phase compared with baseline and washout values. LDL susceptibility to oxidation was tested by oxidation of LDL particles with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). No significant changes were observed for the lag phase and the peroxidation rate. The vitamin E content of LDL also did not change significantly. The results thus suggest that a daily dosage of 2.5 g n-3 fatty acids does not enhance LDL susceptibility to oxidation, while retaining its hypotriacylglycerolemic effect.

Intimal medial thickening of common carotid artery as indicator of coronary artery disease.

The authors investigated the relation between coronary atherosclerosis, angiographically detected, and intimal-medial (I-M) thickening of the common carotid artery (CCA), as measured by high-resolution B-mode ultrasound system. They studied 31 patients with coronary artery disease (CAD) and 23 healthy control subjects. I-M thickening of CCAs and atheromatous plaques at the carotid bifurcation were evaluated. A score system was defined (range 0-20) based on the absence or presence of atherosclerotic lesions at common and internal carotid arteries. A coronary angiography score was defined based on the presence of of atherosclerotic lesions at nine coronary arterial segments (range 0-36). The thickness of CCAs (M +/- SD) in CAD patients was significantly higher (1.45 +/- 0.95 mm) than in controls (0.87 +/- 0.10 mm, P < 0.005), and an I-M thickening of 1.1 mm or more was specific and positively predictive of CAD. A significant positive correlation between coronary and carotid score was observed (P < 0.028, r = 0.373). The study suggests that I-M thickening could be helpful for the identification of patients at risk for CAD.

Wall thickening of common carotid arteries in patients affected by noninsulin-dependent diabetes mellitus: relationship to microvascular complications.

This study evaluates the wall thickness of common carotid arteries and the atherosclerotic involvement of the carotid bifurcations in patients with noninsulin-dependent diabetes mellitus (NIDDM), with and without microvascular complications. Seventy subjects affected by NIDDM, and 17 healthy controls were evaluated by means of high-resolution echo-Doppler scan. Twenty-six diabetics (Group A) and complications (overnight proteinuria > 500 mg, background retinopathy, sensory neuropathy), while 44 (Group B) had no complications. The two groups were comparable for age, sex, plasma lipid profile, and smoking habit. Arterial hypertension was present in 15 of 26 (58%) complicated patients (Group A) and in 18 of 44 (41%) uncomplicated patients (Group B). None of the patients had a history of cerebrovascular disease. The authors found that the wall thickness of the common carotid artery was greater and atherosclerotic lesions of the carotid bifurcation were more frequent in diabetic patients with microvascular complications than in uncomplicated diabetics (who had a similar distribution of other risk factors for atherosclerosis) and in nondiabetic controls. These data on the one hand confirm the role of diabetes as an independent risk factor for carotid atherosclerosis and, on the other hand, indicate a correlation between microvascular lesions and early atherosclerosis in diabetes.

Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients.

The aim of this study was to determine whether gemfibrozil-mediated decrease in very low density lipoprotein triglyceride (VLDL-TG) concentration is accompanied by an improvement in overall glucose metabolism in hypertriglyceridemic patients. We assessed this hypothesis in 7 hypertriglyceridemic without (HTG) and in 11 hypertriglyceridemic with noninsulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-months treatment either with the drug or with placebo. Placebo VLDL-TG concentrations in both HTG (3.82 +/- 0.92 mmol/l (mean +/- S.D.) vs. 3.91 +/- 1.01 mmol/l) and in NIDDM-HTG (6.62 +/- 3.93 mmol/l vs. 6.84 +/- 4.16 mmol/l) were not different from baseline values, whereas gemfibrozil decreased VLDL-TG in both groups (1.84 +/- 0.56 mmol/l, P < 0.001 for HTG, and 1.93 +/- 2.68 mmol/l, P = 0.013 in NIDDM-HTG). In both groups, gemfibrozil treatment was associated with an improvement in fasting plasma glucose levels (from 5.85 +/- 0.92 mmol/l to 4.87 +/- 0.40 mmol/l in HTG, P = 0.001, and from 11.47 +/- 2.92 mmol/l to 9.56 +/- 3.41 mmol/l in NIDDM-HTG, P = 0.042). In NIDDM-HTG, gemfibrozil treatment was associated with a significantly lower 2 h-postprandial plasma glucose level (9.87 +/- 3.63 vs. 13.09 +/- 3.62, P = 0.05). A significant decrease in fasting free fatty acids (FFA) level was observed during gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a significant drop of these substrates was observed in both fasting and postprandial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial mapping with color flow duplex imaging of the lower extremities after excimer-laser-assisted angioplasty.

The purpose of the present study was to evaluate the role of color flow duplex imaging (CFDI) in the follow-up of patients who have undergone excimer-laser-assisted angioplasty of peripheral arteries. Sixty-one patients (40 men and 21 women) were studied (mean age +/- SD sixty-three +/- nine years). All patients were affected by peripheral vascular disease and, for this reason, underwent percutaneous excimer-laser-assisted angioplasty. Digital angiography and CFDI were performed before the laser procedure. CFDI was repeated at months 1, 3, 6, 9, and 12 after the laser procedure, whereas angiography was repeated after twelve months. Common, superficial, and profunda femoral arteries and popliteal arteries were visualized in looking for the presence of lesions and occlusions, and spectral analysis of Doppler signals was recorded. After the initial success, claudication was reported again by 9 patients, 7 of whom showed total occlusions. All reocclusions were discovered by CFDI and confirmed by angiography; 3 of these 7 patients underwent a second laser procedure. The remaining 2 symptomatic patients showed patent vessels and did not undergo angiography. Another 9 patients redeveloped an occlusion, unsuspected from clinical history and symptoms. All the reocclusions, confirmed by angiography, were diagnosed by CFDI. The data show that CFDI provides an accurate noninvasive technique for following up patients after excimer laser angioplasty, allowing for asymptomatic reocclusions to be recognized and treated if necessary, and permitting symptoms not due to reocclusions to be properly identified, thus avoiding unnecessary angiography.

Metabolic effects of dietary stearic acid in mice: changes in the fatty acid composition of triglycerides and phospholipids in various tissues.

The fatty acid patterns of triglycerides and phospholipids extracted from adipose tissue, liver, heart, kidney, spleen, and lung of 3 groups of C57BL/6 mice were determined after feeding diets rich in palmitic acid (16:0) (high palmitic: 16:0 = 45.1% of total fatty acids), stearic acid (18:0) (high stearic: 18:0 = 42.9% of total fatty acids) and oleic acid (18:1) (high oleic: 18:1 = 79.7% of total fatty acids) for 9 months. Triglyceride content of adipose, liver, heart, kidney, lung and spleen tissues was significantly enriched in palmitic acid in mice fed the high palmitic diet (range among all tissues: 19.9% +/- 0.2% to 29.0% +/- 1.9% of total fatty acids) and in oleic acid in mice fed the high oleic diet (range 56.0% +/- 1.9% to 71.6% +/- 1.2%). The stearic acid content of organ triglycerides in mice fed the high stearic diet ranged from 3.7% +/- 0.3% to 10.8% +/- 1.2%; however, the content of oleic acid on this diet (range: 57.0% +/- 1.8% to 71.4% +/- 1.7%) was similar to the one observed in mice fed the high oleic diet. In all organs, phospholipids had a significantly higher percentage of stearic acid (range: 23.5% +/- 0.9% to 51.5% +/- 6.6%) than triglycerides, regardless of diet. To evaluate the production of oleate from stearate and palmitate, 2 groups of mice were fed the high palmitic and the high stearic diets for 1 week and then injected intravenously with [1-14C]palmitate and [1-14C]stearate and the amount of labelled oleate in liver triglycerides was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification.

Oxidized low density lipoproteins (LDLs) are thought to play an important role in atherogenesis. Nutritional and biochemical studies suggest that diet can modulate the susceptibility of plasma LDL to undergo oxidative degradation by affecting the concentration of polyunsaturated fatty acids and antioxidants in the lipoprotein particle. In the present study 11 healthy male volunteers underwent two diet phases. In one phase the diet was enriched in oleic acid (mono), while in the other it was high in linoleic acid (poly). Both diets lowered plasma total and LDL cholesterol contents. The sensitivity of plasma LDL to oxidation was estimated by challenging these lipoproteins with 2,2'-azobis(2-amidinopropane)dihydrochloride, a free-radical initiator. Although neither diet affected the antioxidant content of plasma LDL, the resistance to lipid peroxidation, measured after the consumption of antioxidants present in the lipoprotein, was higher during the mono phase. Indeed, the peroxidation rate of plasma LDL was inversely correlated with the oleic acid to linoleic acid ratio in the LDL particle. These results support the thesis that diets rich in monounsaturated fatty acids increase the resistance of plasma LDL to oxidative modification, independent of their content of antioxidants. This effect could lower the atherogenicity of these lipoproteins.