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Objective: The aim of this study was to evaluate the adherence to recommendations for secondary prevention of cardiovascular diseases in patients with acute coronary syndromes (ACS)., Methods and Results: Physical examination, a careful medical interview with assessment for lifestyle habits, adherence to pharmacological therapy and blood analyses were performed in 130 patients at the time of the acute event and after 6 months of follow-up. At follow-up examination, 7 patients persisted to smoke (5.4%), 41 (31.5%) continued to have high blood pressure, 34 (26.1%) had high levels of total cholesterol, 38 (29.2%) high levels of triglycerides, 64 (49.2%) high levels of LDL-cholesterol and 46 (35.4%) low levels of HDL-cholesterol. Despite all treatments no significant change occurred. A high percentage of patients (47%) reported a lower daily consumption of fruit and vegetables with respect to the recommended daily portions, nearly the whole population (92.3%) did not reach the recommended portions of legumes per week recommended, and a consistent percentage of patients (81.5%) did not consume fish twice a week, as recommended., Conclusion: These findings demonstrate the difficulty of modifying the lifestyle habits in patients with ACS.

Retinal vein occlusion (RVO) is a disease that is often associated with a variety of systemic disorders including arterial hypertension, diabetes mellitus, dyslipidemia and systemic vasculitis. There are various types of RVO, categorized on the basis of the site of occlusion and on the type of consequent vascular damage. Central retinal vein occlusion (CRVO) is the most clinically relevant type of RVO. In addition to well-known classical risk factors, new thrombophilic factors have been investigated in patients with RVO. Data concerning a number of the parameters remain contradictory; yet, hyperhomocysteinemia and vitamins involved in methionine metabolism appear to play a significant role in the pathogenesis of this disease. Alterations in the fibrinolysis pathway (elevated levels of PAI-1 and Lipoprotein (a)), together with haemorheologic modifications have been recently consistently associated with the disease. Medical treatment includes identification and correction of vascular risk factors. In addition, LMWHs appear to be the best therapeutic approach even if based on a limited number of trials, conducted on a limited number of patients. No data are available on the possible role of antithrombotic strategies in the long-term prevention of recurrent RVO or vascular events.

Objective: Carotid stenosis is a common manifestation of systemic atherosclerosis. Apart from traditional risk factors, genetic determinants, such as polymorphisms of the renin angiotensin system (RAS), may be relevant in modulating the atherosclerotic process leading to carotid stenosis. In this study, we investigated the role of angiotensin-converting enzyme (ACE) I/D and -240A>T, angiotensinogen (AGT) M235T, and angiotensin type 1 receptor (AGTR1) 1166A > C polymorphisms in modulating the susceptibility to the disease., Methods: Eight hundred twenty-one consecutive patients with severe carotid stenosis (≥70%) and 847 control subjects were investigated., Results: A significant difference in genotype distribution (P < .0001) and allele frequency (P < .0001) between patients and controls for the ACE I/D polymorphism, but not for the other single-nucleotide polymorphisms investigated, was observed. The ACE D allele frequency was significantly higher in patients without traditional risk factors in comparison with that observed in those with at least one risk factor (0.71 vs 0.61; P = .04). The ACE D allele significantly influenced carotid stenosis under dominant, recessive, and additive model of inheritance at both univariate (P < .0001) and multivariate analysis (P < .0001). When the combined effect of RAS unfavorable alleles was considered, patients carrying less than three alleles had a lower risk of carotid stenosis (odds ratio [OR], 0.79 [0.63-0.99]; P = .05), while carriers of more than four unfavorable alleles had an increased risk (OR, 1.44 [1.12-1.84]; P = .004), in comparison with subjects carrying three or four unfavorable alleles. ACE D allele frequency was similar in patients with and without additional atherosclerotic localizations (0.61 vs 0.62, respectively)., Conclusions: Our findings evidence a role for ACE I/D polymorphism in influencing the susceptibility to carotid stenosis, even in the absence of traditional risk factors. Interestingly, our findings provided further information concerning the role of this polymorphism in modulating the atherosclerotic process apart from its different localizations., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19(*)2 (or 681 G > A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the (*)2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19(*)2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14-3.37); P = 0.02). When studies evaluating stent thrombosis (n = 4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23-6.54); P = 0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19(*)2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.

Purpose: To investigate atherosclerotic and thrombophilic risk factors in patients affected by acute ischemic and nonischemic central retinal vein occlusions (CRVOs)., Methods: One hundred and three patients with acute unilateral CRVO (41 ischemic and 62 nonischemic) were studied. The frequency of traditional cardiovascular risk factors was assessed, and the plasma levels of a variety of thrombophilic markers were measured. Univariate logistic regression was performed to determine risk factors for ischemic CRVO., Results: Arterial hypertension, hypercholesterolemia, postmethionine hyperhomocysteinemia (HHcy), elevated factor VIII, and reduced folic acid and B6 plasma levels were more frequent in patients with ischemic CRVO than in those with nonischemic CRVO (P = 0.030, P = 0.025, P = 0.011, P < 0.001, P < 0.001, and P = 0.044, respectively). Risk factors for ischemic CRVO were arterial hypertension (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.13-9.21; P = 0.037), hypercholesterolemia (OR, 3.03; 95% CI, 1.06-8.65; P = 0.042), reduced folic acid levels (OR, 6.77; 95% CI, 1.59-28.79; P = 0.011), and elevated FVIII levels (OR, 6.17; 95% CI, 2.56-14.82; P < 0.001). Postmethionine HHcy was associated with low folic acid levels (r = -0.413; P = 0.007; OR, 9.33; 95% CI, 2.06-42.18; P = 0.005)., Conclusion: The results of the present study suggest that some atherosclerotic and thrombophilic risk factors may increase the risk of having an ischemic form of CRVO.

Objective: Postoperative atrial fibrillation (AF) is a frequent complication after cardiac surgery. AF may also occur after hospital discharge during postacute rehabilitation. Several studies have addressed the AF that occurs in the hospital after surgery, and predictors have already been identified. Postoperative AF that occurs after hospital discharge has not been investigated thoroughly, and predictors are still unknown. In this study, we hypothesized that moderate-intensity physical activity in the year before surgery might favorably affect the incidence of AF during postacute rehabilitation., Design: We tested our hypothesis in a cohort of 158 older patients admitted to a medical rehabilitation facility for postacute inpatient rehabilitation after coronary surgery and continuously monitored by telemetry for the duration of the rehabilitation., Results: Independent of potential confounders, patients who reported low-intensity physical activity in the year before surgery showed a significantly higher incidence of AF during postacute rehabilitation when compared with those who reported moderate-intensity physical activity (32.1% vs. 8.1%; P = 0.029). Other independent predictors of AF during postacute rehabilitation were the occurrence of AF during the patients' stay in hospital, larger left atrial volume, and lower left atrial emptying fraction., Conclusions: These findings confirm our hypothesis that physical activity in the year before surgery affects the incidence of postoperative AF during postacute rehabilitation. The results also provide information regarding possible predictors that may assist in identifying patients who could benefit from preventive treatments.

Purpose: Epidemiological studies suggest that a moderate consumption of wine is associated with a reduced risk of cardiovascular diseases and with a reduced mortality for all causes, possibly due to increased antioxidant defences. The present intervention study was undertaken to evaluate the in vivo effects of wine polyphenols on gene expression in humans, along with their supposed antioxidant activity., Methods: Blood haemorheology and platelet function were also evaluated. In order to avoid interferences from alcohol, we used de-alcoholised wine (DAW) with different polyphenol content. A randomised cross-over trial of high-proanthocyanidin (PA) red DAW (500 mL/die, PA dose = 7 mg/kg b.w.) vs. low-PA rosé DAW (500 mL/die, PA dose = 0.45 mg/kg) was conducted in 21 post-menopausal women in Florence, Italy. Oxidative DNA damage by the comet assay and gene expression by microarray was measured in peripheral blood lymphocytes, collected during the study period. Blood samples were also collected for the evaluation of haematological, haemostatic, haemorheological, and inflammatory parameters., Results: The results of the present study provide evidence that consumption of substantial amounts of de-alcoholised wine for 1 month does not exert a protective activity towards oxidative DNA damage, nor modifies significantly the gene expression profile of peripheral lymphocytes, whereas it shows blood-fluidifying actions, expressed as a significant decrease in blood viscosity. However, this effect does not correlate with the dosage of polyphenols of the de-alcoholised wine., Conclusions: More intervention studies are needed to provide further evidence of the health-protective effects of wine proanthocyanidins.

Objective: The relationship between physical activity and cognitive function is intriguing but controversial. We performed a systematic meta-analysis of all the available prospective studies that investigated the association between physical activity and risk of cognitive decline in nondemented subjects., Methods: We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to January 2010. Studies were included if they analysed prospectively the association between physical activity and cognitive decline in nondemented subjects., Results: After the review process, 15 prospective studies (12 cohorts) were included in the final analysis. These studies included 33,816 nondemented subjects followed for 1-12 years. A total of 3210 patients showed cognitive decline during the follow-up. The cumulative analysis for all the studies under a random-effects model showed that subjects who performed a high level of physical activity were significantly protected (-38%) against cognitive decline during the follow-up (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54-0.70; P < 0.00001). Furthermore, even analysis of low-to-moderate level exercise also showed a significant protection (-35%) against cognitive impairment (HR 0.65, 95% CI 0.57-0.75; P < 0.00001)., Conclusion: This is the first meta-analysis to evaluate the role of physical activity on cognitive decline amongst nondemented subjects. The present results suggest a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline., (© 2010 The Association for the Publication of the Journal of Internal Medicine.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is a worldwide diffuse condition due to alimentary, environment and genetic factors. The aim of our preliminary study was to evaluate the effectiveness of long-term consumption of food enriched with n-3 polyunsaturated fatty acids (PUFA) in patients with NAFLD., Methods: Eleven patients were enrolled; six (four males, two females) were planned for oral administration of 6.5 ml olive oil enriched with n-3 PUFA for 12 months, while five (four males, one female) were used as controls., Results: Consumption of olive oil enriched with n-3 PUFA demonstrated a significant improvement of liver echo-texture and of the Doppler Perfusion Index after 12 months (after: 0.19 ± 0.02 vs. pre: 0.15 ± 0.03; P < 0.05), whereas no significant changes were seen at the end of follow-up in controls. Moreover, patients who consumed the olive oil enriched with n-3 PUFA showed a significant amelioration of liver enzymes, and of triglycerides (post: 132.8 ± 63.7 vs. pre: 164.5 ± 85.5 mg/dl; P = 0.04) in a general linear model adjusted for age and gender. Interestingly, patients reported to have a significant increase of adiponectin levels (post: 1,487.9 ± 96.7 vs. pre: 1,143 ± 24.8 μg/ml; P = 0.04)., Conclusion: The results of this preliminary study showed that long-term consumption of olive oil enriched with n-3 PUFA in patients with NAFLD is able to decrease circulating liver enzymes and triglycerides, with a significant improvement of adiponectin levels.

Background: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes., Objective: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status., Design: We conducted a comprehensive literature search through electronic databases up to June 2010., Results: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality., Conclusion: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.

Objective: Several biologic mediators and genetic predisposing factors may contribute to the development of peripheral arterial disease (PAD). The eNOS gene, encoding for endothelial nitric oxide synthase, has been proposed as a candidate gene in the predisposition to the disease. In this study, we evaluated the role of eNOS-786T>C, -894G>T and 4a/4b polymorphisms as markers of PAD per se and in the presence of the ACE D allele in patients previously investigated., Methods: We analyzed 281 consecutive patients (220 men, 61 women; median age, 72 years) with PAD and 562 healthy controls, comparable for sex and age., Results: eNOS-786C, but not -894T and 4a, allele frequency was significantly higher in PAD patients than in controls (P = .03). An association with the predisposition to PAD was found for the eNOS-786C allele (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.11-2.09; P = .009) and the eNOS -786C/4a haplotype (OR, 1.41; 95% CI, 1.02-1.94, P = .04) at univariate analysis but not after adjustment for traditional risk factors. When smoking habit was considered, we observed that eNOS-786C/4a haplotype, but not the eNOS-786C allele, influenced PAD predisposition after adjustment for traditional risk factors in smokers (OR, 2.71; 95% CI, 1.38-5.30; P = .004). The eNOS-786C and eNOS-786C/4a haplotype did not modify the susceptibility to PAD in patients carrying the ACE D allele. Nevertheless, the presence of the eNOS-786C/4a haplotype increased PAD predisposition in smokers also carrying ACE D allele (OR, 2.71 to 3.79; P > .05 for interaction)., Conclusions: This study demonstrated an association between eNOS and ACE genes in increasing PAD susceptibility in smokers, thus providing evidence for a gene-environment interaction in modulating predisposition to the disease., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The aim of this study was to evaluate the influence of short-term dietary intake of bread obtained by a selected variety of old grain grown in Tuscany, Italy on some parameters related to the atherosclerotic process. Twenty healthy subjects (median age, 39.5 years) followed for 10 weeks a diet containing bread (150 g/day) made from the test grain (test period) and for the same period a diet containing commercially available bread of the same quantity (control period). Lipid, inflammatory, and hemorheological profiles before and after dietary intervention were evaluated. The test period showed a significant (P < .05) improvement of total cholesterol (pre-intervention, 211.2 +/- 10.8 mg/dL; post-intervention, 196.5 +/- 9.8 mg/dL) and low-density lipoprotein-cholesterol levels (pre-intervention, 137.5 +/- 8.1 mg/dL; post-intervention, 119.5 +/- 7.5 mg/dL), whereas no significant changes during the control period were observed. With regard to inflammatory and hemorheological parameters, the test period showed a significant decrease in some of the parameters investigated (interleukin-8 [pre-intervention vs. post-intervention, 67.4 +/- 10.7 vs. 43.9 +/- 4.1 pg/mL], whole blood viscosity at high [4.36 +/- 0.03 vs. 4.32 +/- 0.03 mPa x s, respectively] and low [26.1 +/- 0.4 vs. 24.8 +/- 0.5 mPa x s, respectively] shear rates, and erythrocyte filtration [8.4 +/- 0.7% vs. 9.1 +/- 0.6%, respectively]) relative to the control period, which showed no significant changes. Short-term dietary intake of whole grain bread obtained from an old grain variety seems to impose a favorable status with regard to lower circulating levels of markers of atherosclerosis.

Introduction: Retinal vein occlusion (RVO) is one of the most common retinal vascular disorders affecting ocular vessels. Few studies, with conflicting results and conducted in limited study populations, have hypothesised the role of high levels of lipoprotein (a) [Lp(a)] in the occurrence of RVO. The aim of this study was to investigate, in a large group of RVO patients, the role of such an emerging thrombophilic parameter on the pathogenesis of RVO., Materials and Methods: We compared 262 patients [median age: 66 years (15-88); 122 M, 140 F] with 262 age- and sex-comparable healthy subjects., Results: Circulating concentrations of Lp(a) were found to be significantly different in patients when compared to healthy subjects [189 (60-1898)mg/L vs. 119.5 (6-1216)mg/L; p<0.0001, respectively]. No significant differences were observed relating to the different types of occlusion (central or branch occlusion). In order to investigate the possible association between high Lp(a) levels and the disease we performed a logistic regression analysis. In the univariate analysis, Lp(a) levels>300mg/L were found to be associated with an increased risk of RVO (OR: 2.39, 95%CI 1.39-3.59; p<0.0001). Following this, three models of multivariate analysis were performed, firstly by adjusting for age, gender, and traditional cardiovascular risk factors, secondly for triglycerides and thirdly for homocysteine levels. In all the models, Lp(a) levels>300mg/L confirmed their role as a risk factor for RVO [first model, OR: 2.15 (95%CI 1.39-3.32), p=0.0001; second model, OR: 3.11 (95%CI 1.77-5.62), p<0.00001; third model, OR: 3.48 (95%CI 1.88-6.43), p<0.00001]., Conclusions: This study reports that, in a large population of RVO patients, high Lp(a) concentrations are significantly related to RVO, independent from other traditional and emerging risk factors, suggesting that they may play a role in its pathogenesis., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

We performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients followed for a time ranging from 14 days to one year, were included. The cumulative analysis reported that residual platelet reactivity despite clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a consistent heterogeneity of the model and evidenced a significant risk of publication bias, so were excluded from the analysis. This exclusion, however, did not influence the overall result, by confirming the increased risk of cardiovascular recurrences for patients with a poor response to clopidogrel treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta-analysis documents a significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events, so suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.

The relationship between protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05-4.12; p<0.00001). On subgroup analysis, a significant association was found between low protein Z levels and arterial vascular diseases (OR 2.67, 95%CI 1.60-4.48; p=0.0002), pregnancy complications (OR 4.17, 95%CI 2.31-7.52; p<0.00001), and venous thromboembolic diseases (OR 2.18, 95%CI 1.19-4.00; p=0.01). The results of this meta-analysis are consistent with a role for protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism.

Background and Aim: Some studies recently reported a favourable effect for cis-9, trans-11 conjugated linoleic acid (CLA) on plasma lipoprotein profile of healthy subjects. Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep's milk naturally rich in CLA on several atherosclerotic biomarkers, in comparison with a commercially available cheese., Methods and Results: Ten subjects (6 F; 4 M) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA (intervention period) and for the same period a diet containing a commercially available cheese of the same quantity (placebo period). Consumption of the dairy product naturally rich in cis-9, trans-11 CLA determined a significant (p<0.05) reduction in inflammatory parameters such as interleukin-6 (pre: 8.08+/-1.57 vs. post: 4.58+/-0.94 pg/mL), interleukin-8 (pre: 45.02+/-5.82 vs. post: 28.59+/-2.64 pg/mL), and tumour necrosis factor-alpha (pre: 53.58+/-25.67 vs. post: 32.09+/-17.42 pg/mL) whereas no significant differences in the placebo period were observed. With regard to haemorheological parameters, the test period significantly ameliorated erythrocytes' filtration rate (pre: 7.61+/-0.71% vs. post: 9.12+/-0.97%; p=0.03) with respect to the placebo period. Moreover, a reduction in the extent of platelet aggregation, induced by arachidonic acid [pre: 87.8+/-1.76% vs. post: 77.7+/-3.56%; p=0.04] was observed during the test period in comparison with the placebo period., Conclusions: Dietary short-term intake of the tested dairy product naturally rich in cis-9, trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers., (Copyright 2009 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by cognitive and memory deterioration, with an increasing prevalence in the industrialized countries and an extraordinary cost of caring for patients. Due to the limited information available on the exact pathophysiology of the disease, over the last years there have been extensive efforts on the identification of possible risk factors, but no conclusive data have been obtained. Some risk factors have been identified but no clear evidence on what is clearly associated with the occurrence and progression of AD are available, and in particular no effective preventive strategies have been found. One of the most intriguing and appealing lines of investigation is the association between lifestyle habits such as diet and dietary compounds and the occurrence of AD. In this review, we focus on studies that investigated the association between nutrition and AD, paying particular attention to the role of a dietary pattern such as a Mediterranean-like diet on the occurrence of such disease. Studies in support of Mediterranean diet as an optimal diet for prevention of cardiovascular and major chronic diseases has rapidly evolved. A recent meta-analysis from our group, comprising prospective studies that investigated the association between adherence to Mediterranean diet and health status, showed a significant association between a greater adherence to Mediterranean diet and a reduced risk of major chronic degenerative diseases, including AD. Moreover, the Mediterranean diet has been extensively reported to be associated with a favorable health outcome and a better quality of life.

Objective: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis. Apart from traditional cardiovascular risk factors, several novel biologic mediators and genetic predisposing factors appear relevant in determining the atherogenetic process leading to PAD. Genes encoding for renin angiotensin system (RAS) components have been proposed as candidate in atherosclerosis. This study investigated four polymorphisms in angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1), genes of RAS, in both predicting PAD and modulating the severity of the disease., Methods: The ACE I/D and -240A>T, AGT M235T, and AGTR1 1166A>C polymorphisms were analyzed in 281 PAD patients and in 485 controls comparable for age and sex., Results: The ACE D and -240T alleles both significantly influenced the predisposition to PAD. The ACE D, but not -240 T, allele remained associated with PAD after Bonferroni correction (P = .004) and adjustment for cardiovascular risk factors (P = .03). The ACE D allele influenced PAD predisposition with a dose-dependent effect (odds ratio for ACE ID vs II genotype, 1.77; P = .006; ACE DD vs II genotype, 2.15; P = .001). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T haplotype significantly and independently influenced the predisposition to PAD (P = .02). In 190 PAD patients with no additional atherosclerotic localizations (isolated PAD), a significant association between ACE D and -240T alleles and PAD was observed. Only the ACE D allele remained associated with isolated PAD after Bonferroni correction (P = .02) and after adjustment for cardiovascular risk factors (P = .02). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T, but not the D/-240A haplotype significantly influenced the predisposition to PAD (P = .0003). No influence of the polymorphisms analyzed on the severity of the disease, according to Rutherford categories, was found., Conclusions: The present study contributes data to highlight the role of the ACED/-240T haplotype in predisposing to PAD, also in the absence of other atherosclerotic comorbidities.

Trans fatty acids are unsaturated fatty acids produced by the partial hydrogenation of polyunsaturated oils. Over the last few years, an increasing interest on these fatty acids has been shown because of their role in the pathogenesis of cardiovascular diseases. To date, major scientific associations strongly recommend consuming a low intake of trans fatty acids for the prevention of cardiovascular diseases, but data on the consumption of these fatty acids in the general population are still lacking. We conducted this observational study on a population of Italian teenagers in order to evaluate the consumption of trans fatty acids in the diet. We studied 81 Italian teenagers, 45 males and 36 females, with a median age of 16 years. To assess their consumption of trans fatty acids, we used the "High School Survey", a questionnaire prepared by the Harvard Medical School. Total calories of the studied population were 2359.2 +/- 591.5 kcal/day with a mean intake of trans fatty acids of 3.24 +/- 1.48 g/day, corresponding to 1.23% of the total energy. A relevant proportion of subjects, namely 51 (62.9%), exceeded the limit contribution of 1% of energy from trans fatty acids. Their intake of total calories and trans fatty acids significantly increased according to their increasing age (p = 0.0003 for trend). Our data, therefore, obtained in a limited population of Italian adolescents, showed that a consistent proportion of adolescents does not follow the nutritional recommendations for intake of trans fatty acids, likely increasing their risk of cardiovascular diseases.

Purpose of Review: The optimal dietary strategy for the prevention of chronic degenerative diseases remains a challenging and a highly relevant preventive health issue. In recent years, there have been ongoing investigations of the effectiveness of the Mediterranean diet in preventing the development of cardiovascular and other chronic diseases. Initial research suggested that the consumption of diets high in vegetable oil, fish, and complex grains and carbohydrates conferred a benefit in reducing the prevalence of cardiovascular disease. The purpose of this review is to examine the evidence in support of the effectiveness of the Mediterranean diet in reducing the prevalence of cardiovascular and chronic disease and their associated risk factors., Recent Findings: Recent studies intended to evaluate the Mediterranean diet in the primary or secondary prevention of cardiovascular and other chronic degenerative diseases have been focused on examining the impact of a whole dietary approach rather than on isolating single nutrients; it is recognized that analyses of single nutrients ignore the important and complex interactions between components of a diet and, more importantly, because people do not eat isolated nutrients. Therefore, dietary scores estimating the adherence to a Mediterranean diet within a population have been developed. Consumption of a Mediterranean diet has been found to be associated with a reduction of overall mortality and a reduced incidence of cardiovascular disease., Summary: The Mediterranean diet has been consistently shown to be associated with favourable health outcomes and a better quality of life. The findings suggest that significant health gains can be expected in a general population whose diet reflects the nutritional principles reflected in a Mediterranean diet.

Objective: Promoting an active lifestyle through an appropriate physical exercise prescription is one of the major targets of cardiac rehabilitation. However, information on the effectiveness of cardiac rehabilitation in promoting lifestyle changes in elderly patients is still scant., Design: In 131 patients over the age of 65 yrs (86 men, and 45 women, mean age 75 yrs +/- 6 SD) who have attended postacute inpatient cardiac rehabilitation after cardiac surgery, we tested the 1-yr adherence to the physical exercise prescription received at the end of the cardiac rehabilitation by using a questionnaire on physical activity and the 6-min walk test., Results: All of the 36 patients who reported an active lifestyle and 49 of the 95 patients who reported a sedentary lifestyle in the year preceding the cardiac operation reported at least 1 hr/day on 5 days each week of light regular physical activity in the year after the cardiac rehabilitation. Further, the distance walked at the follow-up 6-min walk test was significantly related to the physical activity score gathered from the questionnaire., Conclusions: Our data show that 65% of the elderly patients who have attended postacute inpatient cardiac rehabilitation after cardiac surgery are still capable of recovering or even increasing their regular physical activity and of maintaining these favorable lifestyle changes at least for 1 yr.

Background: PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS)., Methods: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations., Results: We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls., Conclusions: The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases.

Background: Previous studies explored the association between hemorheological alterations and acute myocardial infarction, pointing out the role of hematological components on microvascular flow. The aim of this study was to evaluate the association between blood viscosity and infarct size, estimated by creatine kinase (CK) peak activity and cardiac Troponin I (cTnI) peak concentration in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PCI)., Methods: The study population included 197 patients with diagnosis of STEMI undergoing PCI. Hemorheological studies were performed by assessing whole blood viscosity (measured at shear rates of 0.512 s(-1) and 94.5 s(-1)) and plasma viscosity using the Rotational Viscosimeter LS 30 and erythrocyte deformability index by Myrenne filtrometer., Results: Significant correlations between CK peak activity, cTnI peak concentration, left ventricular ejection fraction and hemorheological variables were observed. At linear regression analysis (adjusted for age, gender, traditional cardiovascular risk factors, renal dysfunction, timeliness of reperfusion, pre-PCI TIMI flow, infarct location, multivessel disease and previous coronary artery disease) leukocytes and whole blood viscosity at 0.512 s(-1) and 94.5 s(-1) were independently and positively associated with infarct size., Conclusions: These results demonstrate a significant and independent association between hemorheology and infarct size in STEMI patients after PCI suggesting that blood viscosity, in a condition of low flow, might worsen myocardial perfusion leading to an increased infarct size. The measurement of whole blood viscosity in STEMI patients could help to identify those who may benefit from new therapeutic strategies.

Summary Introduction: Protein Z is a vitamin K-dependent protein that serves as a cofactor for the inhibition of activated factor X by the serpin protein Z-dependent protease inhibitor (ZPI). Protein Z plasma levels have been shown to be reduced in patients with peripheral arterial disease (PAD), but ZPI levels have not yet been reported. The aim of this study was to more fully assess the protein Z-ZPI system in individuals with atherosclerosis selected by the presence of symptomatic PAD., Materials and Methods: Protein Z and ZPI levels were determined in 95 PAD patients (73 males; 22 females) [median age: 73 years (range, 50-86 years)] and in 190 controls comparable for age and gender. Protein Z was measured using a commercial immunoassay, and ZPI was measured with a homemade immunoassay and a functional assay., Results: Protein Z antigen, ZPI antigen and ZPI function were found to be significantly lower in PAD patients with respect to controls [protein Z, median 72.5% (range: 3.4-123.7%) vs. 90.7% (range: 32.1-203.2%), P < 0.0001; ZPI antigen, 86.1% (range: 25.1-149.5%) vs. 93.2% (range: 48.9-171.3%), P = 0.004; ZPI function, 83.5% (range: 21.1-135.2%) vs. 97.2% (range: 50.5-175.5%), P < 0.0001]. The lowest tertiles of protein Z antigen [odds ratio (OR) 5.4, 95% confidence interval (CI) 2.2-13.5, P < 0.0001] and ZPI function (OR 2.4, 95% CI 1.1-5.5, P = 0.03) were associated with PAD on multivariate analysis after adjustment for age, gender, and traditional cardiovascular risk factors. A significant inverse relationship was also observed between protein Z and ZPI levels and the number of traditional cardiovascular risk factors and the clinical severity of disease (Fontaine stage)., Conclusions: Low levels of protein Z antigen and protein Z activity are significantly associated with the occurrence and severity of atherosclerotic PAD.

Background: Non-arteritic anterior ischemic optic neuropathy (NAION) is a multifactorial disease that is caused by an infarction of the vessels that supply the optic nerve head. This study aims at evaluating the role of traditional and emerging cardiovascular risk factors on the development of NAION., Methods: A total of 85 newly diagnosed NAION patients and 107 age- and gender-matched healthy controls were studied. All participants underwent blood testing for homocysteine and lipoprotein(a). Plasma levels of vitamin B6 and B12, and folic acid were also determined. Plasma values of all these parameters were evaluated as continuous variables, by a logarithmic transformation. In addition, traditional cardiovascular risk factors were considered., Results: With univariate analysis, higher values of homocysteine and Lp(a) (OR 4.24, 95% CI 2.01-8.94, p < 0.0001; OR 1.32, 95% CI 1.04-1.67, p = 0.03, respectively) and lower values of vitamin B6 (OR 0.44, 95% CI 0.25-0.76, p = 0.003) were significantly associated with NAION. At multivariate analysis, adjusted for age, gender, smoking habit, hypertension, dyslipidemia, diabetes, sleep apnea, and thrombophilic risk factors, the higher homocysteine and Lp(a) values (OR 5.74, 95% CI 2.41-13.67, p = 0.0001; OR 1.27, 95% CI 1.01-1.63, p = 0.04) and lower vitamin B6 values (OR 0.42, 95% CI 0.23-0.77, p = 0.005) maintained their significant relationship with NAION., Conclusions: This study demonstrated that elevated plasma homocysteine and lipoprotein(a) levels, as well as low vitamin B6 levels, may increase the risk of developing NAION. A screening for these thrombophilic markers could be useful in subjects experiencing NAION.

The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.

No data are available about the possible role of endothelial progenitor cells (EPCs), cytochemokines and N-terminal pro-brain natriuretic peptide (NT-proBNP) in determining a different response to short period of cardiologic rehabilitation (CR), as measured by the improvement of exercise capacity. In a population of 86 cardiac surgery patients, we evaluated the numbers of EPCs, pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, IL-1ra), hs-C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and NT-proBNP before (T1), and after 15 days of CR (T2). EPCs were measured by flow cytometry, and the exercise capacity was measured at T1 and T2 by using the six-minute walk test (6MWT). At T2, a significant increase of 6MWT (p<0.0001) was detected. No significant increase of EPCs was observed, while a significant (at least p<0.05) decrease in cytochemokines, CRP and NT-ProBNP levels was evidenced. By analyzing the median improvement of 6MWT, only patients with a median improvement > or = 23% showed a significant (p<0.05) increase of EPCs at T2, with significant correlations between EPCs, VEGF and IL-10. On the contrary, in patients with a median improvement <23% a negative correlation between CRP and EPCs was observed. Finally, CD34+/KDR+ EPCs showed significant correlation with IL-8 at T1. In conclusion, a short period of CR intervention determines a different pattern of modifications for EPCs in relation to the improvement of exercise capacity.

Mediterranean diet (MD) is an eating pattern that has been worldwide promoted as a model for healthy eating and has been reported to contribute to a favourable health status and to a better quality of life. Over the last years, despite evidences on the beneficial effects of the single components of MD have been reported, research interest has been focused on the whole dietary pattern rather than on a single nutrient, since individual analyses of nutrients and food can ignore important interactions between components of a diet and, more importantly, because people do not eat isolated nutrients. Therefore, dietary scores estimating the adherence to the MD have been operationalised and have been found to be associated with a reduction of overall mortality, cardiovascular diseases, hypertension and obesity. Furthermore, a high degree of adherence to MD has been found related to lower concentrations of inflammation, endothelial dysfunction and coagulation markers. In a recent meta-analysis on over than 1,5 million of persons we were able to demonstrate that a higher adherence to Mediterranean diet is associated with a significant reduced risk of incidence and mortality from all causes and from cardiovascular, neoplastic and neurodegenerative diseases.

Aim: The objective of the present study was to evaluate the influence of short-term dietary intake of farmed fish on biomarkers related to the atherosclerotic process., Methods and Results: Lipid, inflammatory, and haemorheological variables before (T0) and after a dietary intervention with about 800 g Orbetello farmed sea bass per week for 10 weeks (T1) were evaluated in nine dyslipidemic subjects. Fish intake significantly decreased triacylglycerols (T1, 140.2+/-20.3 mg/dl versus T0, 183.3+/-29.2 mg/dl; P =0.04), whereas no significant changes for the other lipid variables have been observed. Moreover, dietary intervention significantly (P <0.05) decreased all of the inflammatory parameters investigated; namely, high-sensitivity C-reactive protein, interleukin-6, and interleukin-8. Furthermore, a significant (P =0.04) improvement in erythrocytes' deformability index was reported after 10 weeks of fish dietary intake (9.0+/-0.7% versus 5.4+/-1.0% for T1 and T0, respectively)., Conclusion: Dietary short-term intake of farmed fish seems to impose favourable biochemical changes in dyslipidemic subjects.

A role of ACE I/D polymorphism in the pathogenesis of abdominal aortic aneurysm (AAA) has been demonstrated, possibly due to the effect of angiotensin II on vascular tissue remodelling. Angiotensin II exerts profibrogenic effects through the local induction of TGF-beta. Dysregulated TGF-beta signalling may result from mutations in TGFBR1 and TGFBR2 genes, thus resulting in degenerative changes in the vessel wall. We performed a case-control study in order to investigate the role of TGFBR1 9A6A polymorphism as predisposing factor to AAA per se, and in the presence of ACE DD and AT1R 1166 CC genotypes in 201 AAA patients (mean age+/-S.D., 71.5+/-6.9) referred to the Unit of Vascular Surgery of the University of Florence, compared with 252 healthy controls (mean age+/-S.D., 70.6+/-8.6). A significant difference in genotype distribution and allele frequency between patients and controls was found for ACE, but not for AT1R and TGFBR1 polymorphisms. At univariate analysis a significant association between ACE DD, but not AT1R CC and TGFBR1 6A allele, and the susceptibility to the disease was found [ACE DD OR=1.86 (95% CI 1.26-2.76), p=0.002]. After adjustment for age, gender, traditional cardiovascular risk factors, and CAD, PAD and CVD, ACE DD genotype still affected the susceptibility to AAA [OR=2.13 (95% CI 1.06-4.28), p=0.03], and the contemporary presence of ACE DD genotype and TGFBR1 6A allele, increased the predisposition to the disease [OR=5.09 (95% CI 1.44-18.02), p=0.01]. This study, which demonstrates an interaction between ACE and TGFBR1 genes in predisposing to AAA, may provide further information on the mechanisms contributing to AAA susceptibility, and offer a topic for future larger studies.

Objective: To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting., Design: Meta-analysis of prospective cohort studies., Data Sources: English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574,299 subjects followed for a time ranging from three to 18 years were included., Results: The cumulative analysis among eight cohorts (514,816 subjects and 33,576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson's disease and Alzheimer's disease (0.87, 0.80 to 0.96)., Conclusions: Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson's disease and Alzheimer's disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.

Background: Recently, a growing body of evidence on the possible role of residual platelet reactivity (RPR) in affecting clinical events has accumulated. The aim of this study was to systematically assess the relationship between RPR on acetylic salicylic acid (ASA) therapy and the occurrence of recurrent events in a meta-analysis of prospective studies., Methods: A systematic literature search of MEDLINE, EMBASE, Science Citation Index, the Cochrane Systematic Review Database and bibliographies of retrieved articles through May 2007 was conducted. Studies were included if they analysed RPR in coronary heart disease patients in relation to the occurrence of adverse coronary events during follow-up., Results: Eleven prospective studies, incorporating 1952 patients with coronary heart disease followed for a time ranging from 6 days to 4 years, met the inclusion criteria. The pooled analysis demonstrated a significantly increased relative risk of adverse clinical events during follow-up for patients with RPR on ASA therapy (RR: 3.11, 95%CI 1.88-5.15; p<0.0001). Moreover, the association between RPR and cardiovascular recurrences remained to be statistically significant even when subgroup analyses performed according to the duration of follow-up, ASA dosage, characteristics of the study population, and laboratory method were conducted., Conclusions: The present meta-analysis documents a significant association between RPR on ASA treatment and recurrent cardiovascular events. More prospective studies are needed to determine the independent prognostic importance of RPR during aspirin therapy and possible benefit of individually tailored anti-platelet treatment strategies in these patients.

The aim of this study was to evaluate hemorheologic variables in patients with acute coronary syndromes in relation to the occurrence of ST-segment elevation myocardial infarction (STEMI). In 370 consecutive patients with acute coronary syndromes, 215 with STEMIs and 155 with non-ST-segment elevation myocardial infarctions or unstable angina pectoris, who underwent percutaneous coronary intervention, hemorheologic studies were performed by assessing whole-blood viscosity (at shear rates of 0.512 and 94.5 s(-1)), plasma viscosity, and erythrocyte deformability index. A significant difference in hematocrit and in whole-blood viscosity at 0.512 s(-1) was found between the 2 groups of patients. Hematocrit at admission in the highest tertile compared with the lowest tertile remained independently associated with the occurrence of STEMI on multivariate analysis adjusted for traditional cardiovascular risk factors, previous coronary artery disease, multivessel disease, bleeding complications, and leukocyte count. In conclusion, erythrocyte concentration seems to play a role per se in the occurrence of STEMI and complete coronary artery occlusion and might be considered in stratifying high-risk cardiovascular patients and as a possible therapeutic target in patients presenting with acute coronary syndromes.

Objective: To evaluate the clinical usefulness of complete preparticipation cardiovascular screening in a large cohort of sports participants., Design: Cross sectional study of data over a five year period., Setting: Institute of Sports Medicine in Florence, Italy., Participants: 30,065 (23,570 men) people seeking to obtain clinical eligibility for competitive sports., Main Outcome Measures: Results of resting and exercise 12 lead electrocardiography., Results: Resting 12 lead ECG patterns showed abnormalities in 1812 (6%) participants, with the most common abnormalities (>80%) concerning innocent ECG changes. Exercise ECG showed an abnormal pattern in 1459 (4.9%) participants. Exercise ECG showed cardiac anomalies in 1227 athletes with normal findings on resting ECG. At the end of screening, 196 (0.6%) participants were considered ineligible for competitive sports. Among the 159 participants who were disqualified at the end of the screening for cardiac reasons, a consistent proportion (n=126, 79.2%) had shown innocent or negative findings on resting 12 lead ECG but clear pathological alterations during the exercise test. After adjustment for possible confounders, logistic regression analysis showed that age >30 years was significantly associated with an increased risk of being disqualified for cardiac findings during exercise testing., Conclusions: Among people seeking to take part in competitive sports, exercise ECG can identify those with cardiac abnormalities. Follow-up studies would show if disqualification of such people would reduce the incidence of CV events among athletes.

Background: A vast body of evidence during the last decades has shown the clear preventive role of physical activity in cardiovascular disease. The real magnitude of the association between physical activity during leisure time (LTPA) and primary prevention of coronary heart disease (CHD) has, however, not been completely defined., Design: Meta-analysis of prospective cohort studies., Methods: Studies were included if they reported relative risks and their corresponding 95% confidence intervals (CI), for categories of LTPA in relation to CHD. The LTPA categories of the selected studies were grouped into three levels of intensity: high, moderate and low. The high level of physical activity was determined, to obtain a level of intensity attainable by the general population., Results: Data were available for 26 studies, incorporating 513,472 individuals (20,666 CHD events), followed up for 4-25 years. Under a random-effects model, the overall analysis showed that individuals who reported performing a high level of LTPA had significant protection against CHD [relative risk 0.73 (95% CI 0.66-0.80), P<0.00001]. A similar significant protection against CHD, for individuals who practised a moderate level of LTPA, has been also demonstrated [relative risk 0.88 (95% CI 0.83-0.93), P<0.0001]., Conclusions: The current meta-analysis reports significant protection against the occurrence of CHD resulting from moderate-to-high levels of physical activity. These results strengthen the recommendations of guidelines that indicate the protective effect against cardiovascular disease of physical activity profiles that are attainable by ordinary people.

Retinal vein occlusion (RVO) is one of the most common retinal vascular disorders. During the last years, high levels of homocysteine (Hcy) have been demonstrated to be an independent risk factor for RVO. Aim of this study was to investigate the association among circulating B-group vitamins, Hcy and RVO. Thus, we studied 262 RVO patients and 262 age- and sex-comparable healthy subjects. Serum vitamin B6 was measured by HPLC, serum folic acid and vitamin B12 by radioimmunoassay and plasma Hcy by FPIA. Blood levels of vitamin B6, folate and Hcy, but not of vitamin B12, were found to be significantly different in patients as compared to healthy subjects. At the univariate analysis, the lowest tertile of vitamin B6 [odds ratio (OR) 4.03; 95% confidence interval (CI) 2.58-6.31; P<0.0001)] and folate (OR 6.13; 95% CI 3.85-9.76, P<0.0001), and the highest tertile of Hcy (OR 8.08; 95% CI 5.05-12.92, P<0.0001) were found to be significantly associated with RVO. Moreover, at multivariate analysis, after adjustment for traditional cardiovascular risk factors, Hcy, and circulating levels of vitamins, respectively, the lowest tertile of vitamin B6 (OR 3.29; 95% CI 1.89-5.70, P<0.0001) and folate (OR 5.41; 95% CI 3.08-9.51, P<0.0001) and the highest tertile of Hcy (OR 2.58; 95% CI 1.12-5.94, P<0.0001) maintained their significant association with RVO. In conclusion, the present study documents, on a large sample of patients, that low vitamin B6 levels, low folic acid levels and elevated Hcy levels are each independently associated with RVO.

Purpose: Atherosclerotic and thrombophilic risk factors may be causes of central retinal vein occlusion (CRVO). The aim of this study was to evaluate the prevalence of the aforesaid risk factors in patients with recurrent CRVOs and patients with a single episode of CRVO., Methods: Seventeen patients with recurrent CRVO and 30 with a single episode of CRVO were enrolled. The atherosclerotic risk factors investigated were hypertension, diabetes, smoking, and dyslipidemia. Specific laboratory tests for the following thrombophilic markers were performed: homocystinemia (Hcy), lipoprotein (a), factor VIII, factor II G20210A and factor V G1691A polymorphisms, lupus anticoagulant, anticardiolipin antibodies, plasminogen activator inhibitor-1, and deficit of vitamins B6, B12, and folic acid. A multivariate analysis, adjusted for age, gender, traditional and thrombophilic risk factors, was performed. Statistical significance was set at p

Background: A large number of studies have demonstrated that regular physical activity during leisure time (LTPA) accounts for a significant protection against cardiovascular diseases (CVD). On the other hand, conflicting findings on the beneficial effects of occupational physical activity (OPA) have been reported. The aim of this study is to evaluate the possible influence of different amounts of LTPA and OPA on circulating levels of several parameters associated with an increased risk of CVD., Materials and Methods: We studied 932 individuals (365 M; 567 F, with a mean age of 54 years) living in Florence, Italy, who were enrolled in a population study conducted between 2002 and 2004. Subjects were divided into three classes of LTPA and OPA according to a score derived from a questionnaire that assessed the amount of physical activity performed., Results: LTPA was inversely related to body mass index (BMI), hip circumference, diastolic blood pressure and triglycerides, as well as directly correlated with high-density lipoprotein (HDL) cholesterol. Likewise, a higher OPA was found to be associated with higher HDL cholesterol levels. Moreover, a multivariate logistical regression analysis, adjusted for possible confounders, showed that a moderate-to-high intensity of LTPA was able to confer a significant protection against having abnormal levels of BMI, waist circumference and triglycerides, main features of the metabolic syndrome, whereas no associations between these parameters and OPA were observed., Conclusions: A moderate-to-high LTPA was found to be significantly associated with a more favourable cardiovascular risk profile in terms of anthropometric, metabolic and lipid parameters among an Italian population. In addition, a relationship between OPA and HDL-cholesterol was reported.

High plasma lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for atherosclerotic diseases. To date, no effective intervention strategies on reducing Lp(a) concentrations have been reported. The aim of the study was to evaluate the possible modulation of two polymorphisms of LPA gene (LPA 93C>T and LPA 121G>A) and nutritional habits on Lp(a) concentrations. We studied 647 healthy Italian subjects (260 M; 387 F) with a median age of 48 years (range: 19-78) enrolled in an epidemiological study conducted in Florence, Italy. A linear regression analysis showed a significant negative influence of fish intake (beta=-0.174+/-0.084; p=0.04) on Lp(a) concentrations, after adjustment for smoking habit, C-reactive protein serum concentrations, dietary habits and LDL-cholesterol concentrations. With regard to LPA polymorphisms, LPA 93C>T polymorphism resulted to significantly affect Lp(a) circulating concentrations in a dose-dependent manner, with lower concentrations shown by subjects carrying the T rare allele, whereas no significant influence of LPA 121G>A polymorphism on Lp(a) concentrations was observed. Moreover, by analyzing the possible interplay between LPA 93C>T and dietary fish intake, a significant interaction between these two determinants in lowering Lp(a) concentrations was reported. In addition, lower Lp(a) concentrations were observed in subjects carrying the T allele of the LPA 93C>T polymorphism and consuming a high intake of fish with respect to those being in the highest tertile of fish consumption but homozygotes for the common allele of the polymorphism. In conclusion, this study reported a significant interaction of daily fish intake and LPA 93C>T polymorphism in decreasing Lp(a) concentrations.

Retinal vein occlusion (RVO) is an important cause of permanent visual loss. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of RVO. Aim of this case-control study was to evaluate the possible association between haemorheology and RVO. In 180 RVO patients and in 180 healthy subjects comparable for age and gender we analysed the whole haemorheological profile: [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV), and fibrinogen]. WBV and PLV were measured using a rotational viscosimeter, whereas DI was measured by a microcomputer-assisted filtrometer. WBV at 0.512 sec(-1) and 94.5 sec(-1) shear rates as well as DI, but not PLV, were found to be significantly different in patients as compared to healthy subjects. At the logistic univariate analysis, a significant association between the highest tertiles of WBV at 94.5 sec(-1) shear rate (OR: 4.91, 95% CI 2.95-8.17; p < 0.0001), WBV at 0.512 sec(-1) shear rate (OR: 2.31, 95% CI 1.42-3.77; p < 0.0001), and the lowest tertile of DI (OR: 0.18, 95% CI 0.10-0.32; p < 0.0001) and RVO was found. After adjustment for potential confounders, the highest tertiles of WBV at 0.512 sec(-1) shear rate (OR: 3.23, 95% CI 1.39-7.48; p = 0.006), WBV at 94.5 sec(-1) shear rate (OR: 6.74, 95% CI 3.06-14.86; p < 0.0001) and the lowest tertile of DI (OR: 0.20,95% CI 0.09-0.44, p < 0.0001) remained significantly associated with the disease. In conclusion, our data indicate that an alteration of haemorheological parameters may modulate the susceptibility to the RVO, by possibly helping to identify patients who may benefit from haemodilution.

Background and Aim: During the last 5 years, an increasing body of evidence on the association between adherence to the Mediterranean diet (MD), calculated through specific diet scores, and health status have been accumulated, but limited data are available regarding the association between MD scores and biomarkers. Similarly, many studies have demonstrated a significant protection against chronic diseases from a global healthy lifestyle (HL) pattern which includes not only dietary habits but also physical activity and abstinence from smoking, whereas few data regarding the influence of a HL pattern on circulating biomarkers are available. Using the framework of an epidemiological study conducted in Florence, Italy between 2002 and 2004 we evaluated the association between two different scores (a score of adherence to the MD and a score of adherence to a healthful life which includes abstinence from smoking and a moderate-to-high physical activity level) and some circulating parameters linked to chronic diseases., Methods and Results: Dietary habits and anthropometric and biochemical profiles were studied in 932 individuals (365 M; 567 F) with a median age of 47.5 years. Subjects who reported a greater adherence to the MD were found more frequently to be male, married and over 45 years of age. A general linear model dividing the study population into quartiles of scores was used. After adjustment for age, gender, educational status, body mass index and total energy intake, we observed no influence of adherence to the MD on circulating levels of biomarkers. On the other hand, an inverse association between circulating levels of lipid parameters (namely total cholesterol, LDL-cholesterol and triglycerides) and higher scores of adherence to a HL, was reported. In addition, a significant difference between the highest and the lowest quartiles of HL scores for homocysteine plasma levels was observed (p=0.04)., Conclusion: A high adherence to a HL, which includes not only a high adherence to the MD but also to other lifestyle factors (i.e. abstinence from smoking, and increasing physical activity during leisure time), is able to lower lipid parameters and homocysteine in a clinically healthy Italian population.

Conflicting findings regarding the association between protein Z and atherosclerotic disease have been reported. The aim of this case-control study was to evaluate the role of protein Z in a peripheral localization of atherosclerosis. We studied protein Z levels in 120 patients (102 male, 18 female; median age: 75 years) admitted to the Unit of Vascular Surgery of the University of Florence with a clinical manifestation of peripheral arterial disease (PAD), and in 360 healthy subjects selected to be comparable to the patients group in terms of age and gender. Protein Z levels were found to be significantly (p<0.05) lower in PAD patients [1,594 (89-3,635) ng/ml] compared to the healthy control group [1,728 (300-3,736) ng/ml]. A logistic regression analysis showed, at univariate analysis, a significantly increased risk of PAD in patients with low levels of protein Z (<5th percentile of our control group: <601 ng/ml) (OR: 5.72, 95%CI 3.07-10.66; p<0.0001). After adjustment for age, gender and traditional cardiovascular risk factors the association was confirmed (OR: 5.83, 95%CI 2.83-12.01; p<0.0001). Moreover, a significant association between low protein Z levels and clinical severity of the disease, evaluated through Fontaine's stages, was reported after adjustment for age, gender, and traditional cardiovascular risk factors (general linear model, p for trend: 0.03). In conclusion, our data shows an association between low protein Z levels and the occurrence of PAD. These findings provide evidence for the role of protein Z in the pathogenesis of the atherosclerotic disease.

Background: Lipoprotein (a) [Lp(a)], a low-density lipoprotein particle linked to apolipoprotein (a), has been recently demonstrated to be an independent risk factor for arterial vascular diseases. However, despite increasing evidence of the association between high Lp(a) and arterial thrombotic diseases, few and conflicting results on the association between high Lp(a) levels and venous thromboembolism have been obtained. The aim of this article is to systematically examine the published data on the association between high Lp(a) levels and venous thromboembolism., Methods: A systematic search of all publications listed in the electronic databases (Medline, EMBASE, Web of Science, and The Cochrane Library) up to November 2006, using keywords in combination both as MeSH terms and text words, was conducted., Results: Six case-control studies were included, incorporating 1826 cases of venous thromboembolism and 1074 controls. The summary odds ratios of included case-control studies under a fixed-effects model showed a statistically significant association between Lp(a) levels >300 mg/L and venous thromboembolism: 1.87, 95% confidence interval (CI), 1.51-2.30; P <.0001. Furthermore, a random-effects model, which accounts for the interstudy variation, yielded a similar estimate of increased risk (odds ratio [OR] 1.77; 95% CI, 1.14-2.75; P=.01)., Conclusions: The present meta-analysis shows a significant association between high Lp(a) levels and the occurrence of venous thromboembolism in adults. Indeed, the detection of Lp(a) could be of clinical relevance for venous thromboembolism, especially among patients with absence of traditional and thrombophilic risk factors.

Background: Inflammatory markers are involved in heart failure (HF) pathophysiology. However, the link between these markers and reverse remodeling as well as major adverse cardiac events (HF death, sudden death, and unplanned cardiac rehospitalizations) in patients who undergo cardiac resynchronization therapy (CRT) has not been evaluated., Methods and Results: We recorded major adverse cardiac events of 140 patients (on optimized medical therapy, left ventricular ejection fraction 29.9 +/- 9.6%, New York Heart Association Class III-IV, with intraventricular dyssynchrony) who underwent CRT (enrolled since April 2004). Moreover, we evaluated before and after 6 months of CRT: interleukin-6, high-sensitivity C-reactive protein, New York Heart Association class, quality of life (score on Minnesota Living with Heart Failure questionnaire), 6-minute walking test, left ventricular end-diastolic and end-systolic volumes (nonindexed and indexed by body surface area), and left ventricular ejection fraction. Adverse cardiac events were observed in 40 patients (28.6%): 22 deaths and 18 cardiac unplanned rehospitalizations. Only patients without adverse events during follow-up showed a significant reduction of inflammatory markers and left ventricular volumes (reverse remodeling), despite a significant improvement of clinical status observed in both groups of patients., Conclusions: The reduction of inflammatory status seems to be linked to reverse remodeling as well as to a better clinical prognosis in patients with HF who underwent CRT.

Background and Aims: During the past three decades the relationship between habitual coffee drinking and coronary heart disease (CHD) has been assessed in numerous studies, with conflicting results. The aim of this study was to systematically examine the data published on the association between habitual coffee consumption and risk of CHD., Methods and Results: Thirteen case-control and 10 cohort studies were included. Case-control studies incorporated 9487 cases of CHD and 27,747 controls, and cohort studies included a total of 403,631 participants that were followed for between 3 and 44 years. The summary of odds ratios (OR) for the case-control studies showed statistically significant associations between coffee consumption and CHD for the highest intake group (>4 cups/day), OR 1.83 (95% CI 1.49-2.24; P<0.0001), and for the second highest category (3-4 cups/day), OR 1.33 (95% CI 1.04-1.71; P<0.0001), while no significant association emerged for low daily coffee intake (< or =2 cups/day), OR 1.03 (95% CI 0.87-1.21; P=0.45). The analysis of long-term follow-up cohort studies did not show any association between the consumption of coffee and CHD, with a relative risk (RR) of 1.16 (95% CI 0.95-1.41; P=0.14) for the highest category, and 1.05 (95% CI 0.90-1.22; P=0.57) and 1.04 (95% CI 0.90-1.19; P=0.60) for the second and third highest categories, respectively. These results did not differ substantially when controlling for region of origin, fatal and non-fatal events, year of publication, and number of years of follow-up., Conclusions: Despite a significant association between high consumption of coffee and CHD reported among case-control studies, no significant association between daily coffee consumption and CHD emerged from long-term follow-up prospective cohort studies.

During the last years, a growing body of evidence has been accumulated on the role of hyperhomocysteinemia in the occurrence of coronary artery disease and other arterial occlusive diseases. The mechanism by which high circulating homocysteine concentrations are a risk factor for atherothrombosis is incompletely understood. The present review is aimed to evaluate the role of inflammation in influencing homocysteine (Hcy) and vitamin B(6) concentrations. Results of a large population-based study have suggested that inflammatory markers are the major determinants of Hcy and vitamin B(6) concentrations. This association, independent of the leading factor, may explain, at least in part, why subjects with high concentrations of Hcy and low concentrations of vitamin B(6) have a high risk of developing cardiovascular diseases.

Background: The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude-associated hypoxia., Methods and Results: In a double-blind fashion, healthy volunteers were randomly assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2 days; n=10) or placebo (n=10) at sea level and after rapid ascent to high altitude (4559 m). At sea level, bosentan did not induce any significant changes in hemodynamic or renal parameters. At altitude, bosentan induced a significant reduction of systolic pulmonary artery pressure (21+/-7 versus 31+/-7 mm Hg, P<0.03) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment. However, both urinary volume and free water clearance (H2OCl/glomerular filtration rate) were significantly reduced versus placebo after 2 days of ET-1 antagonism (1100+/-200 versus 1610+/-590 mL; -6.7+/-3.5 versus -1.8+/-4.8 mL/min, P<0.05 versus placebo for both). Sodium clearance and segmental tubular function were not significantly affected by bosentan administration., Conclusions: The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation. These findings must be considered for the prevention and treatment of acute mountain sickness.