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Background: Beneficial effects of vegetarian and vegan diets on health outcomes have been supposed in previous studies., Objectives: Aim of this study was to clarify the association between vegetarian, vegan diets, risk factors for chronic diseases, risk of all-cause mortality, incidence, and mortality from cardio-cerebrovascular diseases, total cancer and specific type of cancer (colorectal, breast, prostate and lung), through meta-analysis., Methods: A comprehensive search of Medline, EMBASE, Scopus, The Cochrane Library, and Google Scholar was conducted., Results: Eighty-six cross-sectional and 10 cohort prospective studies were included. The overall analysis among cross-sectional studies reported significant reduced levels of body mass index, total cholesterol, LDL-cholesterol, and glucose levels in vegetarians and vegans versus omnivores. With regard to prospective cohort studies, the analysis showed a significant reduced risk of incidence and/or mortality from ischemic heart disease (RR 0.75; 95% CI, 0.68 to 0.82) and incidence of total cancer (RR 0.92; 95% CI 0.87 to 0.98) but not of total cardiovascular and cerebrovascular diseases, all-cause mortality and mortality from cancer. No significant association was evidenced when specific types of cancer were analyzed. The analysis conducted among vegans reported significant association with the risk of incidence from total cancer (RR 0.85; 95% CI, 0.75 to 0.95), despite obtained only in a limited number of studies., Conclusions: This comprehensive meta-analysis reports a significant protective effect of a vegetarian diet versus the incidence and/or mortality from ischemic heart disease (-25%) and incidence from total cancer (-8%). Vegan diet conferred a significant reduced risk (-15%) of incidence from total cancer.

Objective: To investigate lipoprotein(a) [Lp(a)], a well known cardiovascular risk factor, in women with history of placenta-mediated pregnancy complications (PMPC) compared with healthy uneventful-pregnancy women (HW), and the role of LPA gene functional polymorphisms in modulating both Lp(a) levels and PMPC risk., Design: Retrospective observational study., Setting: University hospital., Patient(s): A total of 360 women with history of PMPC (154 preeclampsia [PE], 121 stillbirth [SB], and 85 small for gestational age [SGA]) and 270 HW., Intervention(s): Not applicable., Main Outcome Measure(s): Lp(a) levels measurement and LPA +93C >T and +121G>A polymorphisms genotyping., Result(s): In PMPCs we observed higher Lp(a) levels than those found in HW and an association with PMPC risk, also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring 2.5-fold and 2-fold increased risks, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk., Conclusion(s): We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: A history of placenta-mediated pregnancy complications (PMPCs) increases the risk of cardiovascular disease later in life, possibly related to the persistence of endothelial dysfunction. We performed this study in order to search for a common genetic background shared by women with a history of PMPC and vascular disorders, due to their common pathophysiologic pathway of endothelial dysfunction., Methods: We analyzed the prevalence of seven polymorphisms in ACE, AGTR1, AGT, and eNOS genes, endothelial-function related, in 290 women with a history of premature cardiovascular events (CVDs), and in 367 women with a history of PMPC (preeclampsia (PE), stillbirth (SB), and small for gestational age (SGA)), compared with 300 healthy women (HW) who delivered after uneventful pregnancy (HW)., Results: ACE D allele frequency was similar between women with history of CVD and PMPC, and significantly higher than that observed in HW [OR (95% CI) 1.91, p = 0.002, and OR (95% CI) 2.18, p < 0.0001, respectively]. In women carrying ACE-240T or eNOS-786C allele, a two-fold increase in SB susceptibility was evidenced (p = 0.004 and p = 0.005, respectively). Women with a history of SB and premature CVD exhibited a significantly higher unfavorable allelic burden ≥ 3 in comparison to that observed in HW (p < 0.0001 and p = 0.002, respectively)., Conclusions: Our findings demonstrate a common genetic background shared by women with a history of vascular disorders and PMPCs; pregnancy may be considered a window to future cardiovascular risk; therefore, "non-classic" genetic biomarkers of endothelial dysfunction might allow one to identify women who could have a greater benefit for an early cardiovascular screening and prevention.

Objective: To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet., Design: We conducted a comprehensive literature search through all electronic databases up to June 2013., Setting: Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained., Subjects: The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses., Results: A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet., Conclusions: The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.

Cardiovascular diseases actually remain the leading cause of death and morbidity in Western countries, and it is the most common cause of death in American women accounting for about one third of all deaths. Women remain underrepresented in published trial literature relative to their disease prevalence. Strong evidence do exists demonstrating gender differences in efficacy (ischemic risk) and safety (bleeding risk) associated with antithrombotic treatment, mostly related to different values of body mass, and renal function in women than men. Several data show a higher platelet reactivity in females and a higher prevalence of high platelet reactivity on aspirin and clopidogrel therapy. In primary prevention, the use of aspirin is associated with a higher reduction of risk for ischemic stroke in females and for myocardial infarction in males. In the setting of ACS, female gender is associated with a significantly higher risk of bleeding. In summary, there are some gender-related aspects of guidance in the complex spectrum of the net clinical benefit related to antithrombotic treatment.

Objective: Increasing evidence suggests an association between insomnia and cardiovascular disease. We performed a systematic review with meta-analysis of all the available prospective studies that investigated the association between insomnia and risk of developing and/or dying from cardiovascular disease., Design: Systematic review and meta-analysis of prospective cohort studies., 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 December 2011. Studies were included if they were prospective, had assessment of insomnia or sleep complaints at baseline, evaluated subjects free of cardiovascular disease at baseline and measured the association between insomnia and risk of developing and/or dying from cardiovascular disease., Results: After the review process 13 prospective studies were included in the final analysis. These studies included 122,501 subjects followed for a time ranging from three to 20 years. A total of 6332 cardiovascular events occurred during the follow-up. Insomnia was assessed through questionnaire and defined as either difficulty of initiating or maintaining sleep or presence of restless, disturbed nights. The cumulative analysis for all the studies under a random-effects model showed that insomnia determined an increased risk (+45%) of developing or dying from cardiovascular disease during the follow-up (relative risk 1.45, 95% confidence interval 1.29-1.62; p < 0.00001), with no evidence of heterogeneity across the studies (I 2: 19%; p = 0.14)., Conclusion: Insomnia is associated with an increased risk of developing and/or dying from cardiovascular disease.

Over the last years, numerous evidence on the existing relationship between nutrition and chronic degenerative diseases have led investigators to search for the optimal dietary pattern to maintain a good health status. It's well known, in fact, that nutrition is capable of substantially modifying the risk profile ofa subject in primary and/or secondary prevention. Several models of diet have been imposed on public attention, but the one that got the most interest is certainly the Mediterranean diet. Recently, several studies have shown that a strict adherence to a Mediterranean dietary pattern is associated with a lower incidence of mortality and incidence of chronic degenerative diseases such as cardiovascular disease and cancer. Meta-analyses conducted by our group have revealed, in a population of over than 2 million of people, that adherence to Mediterranean diet determines a significant reduction on the risk of cardiovascular and cerebrovascular accidents. To the best of the knowledge the most effective indications for an optimal therapeutic strategy in nutrition include: increase the consumption of fruits and vegetables up to the recommended 5 servings a day, prefer whole grains, replace saturated and trans fats with unsaturated fats, reduce the consumption of sugar and sweetened beverages, and limit salt intake. With these simple indications, together with recommendations of following the principles of the traditional Mediterranean diet, a substantial reduction of the risk of incidence and/or mortality from cardiovascular disease can be easily obtained.

Since the mid '90s, the concept of evidence-based medicine has grown exponentially, contributing to the advancement of personalized medicine, which considers the "female gender" as an extremely important area of customization, but orphan of targeted research. Strong evidence do exists demonstrating gender differences in bleeding risk associated with antithrombotic treatment, mostly related to lower values of body mass, organ size and renal function in women than men. Across clinical studies, the search for the specific risk of bleeding in the female vs male gender has gained attention only recently; therefore, data from different studies and relatively limited meta-analyses should be assessed carefully. As for antiplatelet therapy for primary prevention, the risk of major bleeding events, such as cerebral hemorrhage, is lower for women than for men. Conversely, in acute situations in which antithrombotic drugs are given in association, the risk of bleeding is greater for women, in particular for combination therapies with heparin or low molecular weight heparin or thrombolytic agents. Numerous studies in the literature evaluated the incidence of minor and major bleeding during oral anticoagulant therapy in relation to gender, but the results are not entirely consistent and appear to vary over the years. In summary, there are some aspects of guidance in the complex spectrum of the bleeding risk related to antithrombotic treatment, with indications of a lower bleeding risk in women than men related to long-term preventive single antithrombotic drug treatments. In addition, hormonal effects and use of outprescribed drugs may also play a significant role in modulating hemostasis.

Atherosclerosis is the main cause of morbidity and mortality in the Western world. Inflammation and blood flow alterations are new markers emerging as possible determinants for the development of atherosclerotic lesions. In particular, blood flow exerts a shear stress on vessel walls that alters cell physiology. Shear stress arises from the friction between two virtual layers of a fluid and is induced by the difference in motion and viscosity between these layers. Regions of the arterial tree with uniform geometry are exposed to a unidirectional and constant flow, which determines a physiologic shear stress, while arches and bifurcations are exposed to an oscillatory and disturbed flow, which determines a low shear stress. Atherosclerotic lesions develop mainly in areas of low shear stress, while those exposed to a physiologic shear stress are protected. The presence of areas of the arterial tree with different wall shear stress may explain, in part, the different localization of atherosclerotic lesions in both coronary and extracoronary arteries. The measurement of this parameter may help in identifying atherosclerotic plaques at higher risk as well as in evaluating the efficacy of different pharmacological interventions. Moreover, an altered shear stress is associated with the occurrence of both aortic and intracranial aneurysms, possibly leading to their growth and rupture. Finally, the evaluation of shear stress may be useful for predicting the risk of developing restenosis after coronary and peripheral angioplasty and for devising a coronary stent with a strut design less thrombogenic and more conducive to endothelization., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Renal transplant recipients (RTRs) patients are at increased risk of cardiovascular morbidity and mortality. We aimed this study to assess reticulated platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA) treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the percentage of RP of the total optical platelet count (immature platelet fraction; IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA) induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 μM ADP (ADP2-PA and ADP10-PA) and 2 μg/ml collagen (Coll-PA). vWF levels were measured by using a miniVidas analyser. Group A and group B showed significant higher values of RP than controls. At a multiple linear regression analysis IPF and IPF# were significantly and positively related to collagen-PA. By analysing group B according to residual platelet reactivity (RPR), we observed a significant higher number of RP among patients with RPR by collagen. Moreover at a multiple logistic regression analysis, IPF# significantly affected the risk of having a RPR by collagen. With regard to vWF, RTRs patients showed higher levels than control subjects. We documented a higher platelet turn-over in both groups of RTRs patients and increased platelet reactivity in RTRs patients not on ASA therapy than controls.

The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 17% to 33% in the general population. It is frequently associated with obesity (60-90%), dyslipidemia (27-92%), diabetes (28-55%) and arterial hypertension (22%); in the presence of the metabolic syndrome, its incidence is 2-fold higher. NAFLD can be considered as an early mediator of the atherosclerotic process with which it shares some pathogenetic mechanisms (insulin resistance, oxidative stress, endothelial dysfunction, inflammatory activation). Patients with NAFLD are usually asymptomatic, high values of liver enzyme tests being the most common finding. Although liver biopsy is the current gold standard for diagnosis of NAFLD, it is not a practical screening tool given the cost, time-consuming nature and potential morbidity of this procedure. Ultrasound is a relatively inexpensive technique of liver imaging. Patients with NAFLD exhibit a higher mortality rate than the general population. The most frequent causes of death are represented by liver-related diseases, malignant neoplasms and cardiovascular disease, the latter being as frequent as malignant neoplasms. Data on cardiac abnormalities in patients with NAFLD are scarce. Abnormalities in left ventricular geometry and diastolic function have been described in patients with NAFLD as well as a more severe coronary artery disease characterized by vulnerable plaques, though observed in small cohort studies. According to the available evidence, NAFLD should be taken into consideration by cardiologists because its identification allows a better risk stratification in both primary and secondary prevention. Its correlation with coronary artery disease strongly suggests that NAFLD plays a proatherogenic role per se, in addition to the well known atherosclerotic risk factors. The finding of increased fatty liver content should prompt to assess the coexistence of other risk factors as well as to tailor the appropriate therapeutic regimen in order to reduce fatty liver content.

There is some data available on the role of high on-treatment platelet reactivity by ADP whereas, as regards arachidonic acid or other agonists, there is no proof of the best cut-off for identifying populations with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics (ROC) curves. We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) with stent implantation and followed them up for 12 months. Platelet reactivity was assessed by light transmission aggregometry (LTA) using 10 microM ADP, 1 mM arachidonic acid (AA) and 2 microg/ml collagen. At a 12-month follow-up, we found 37 cardiovascular deaths (3.3%), 54 non-fatal myocardial infarctions (MI) (4.8%) and 154 target vessel revascularisations (TVR) (13.8%). ROC analysis demonstrated that 10 microM ADP LTA, 1 mM AA and 2 microg/ml collagen LTA were able to distinguish between patients with and without subsequent cardiovascular death and non-fatal MI (area under the curve for 10 microM ADP 0.63 (0.55-0.71), p<0.001; for 1 mM AA 0.68 (0.61-0.76), p<0.0001; for 2 microg/ml collagen 0.62 (0.52-0.73), p<0.0111), whereas no association was demonstrated with the occurrence of TVR. Ten microM ADP LTA>or=55%, 1 mM AA LTA>or=15% and 2 microg/ml collagen LTA>or=31% were identified as the optimal cut-off to predict cardiovascular death and non-fatal MI at 12-month follow-up. The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI, whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [10 microM ADP LTA>or=55% + 1 mM AA LTA>or=15%: odds ratio [OR]=3.6(2.4-6.1), p<0.0001; ADP LTA>or=55% + 1 mM AA LTA>or=15% + 2 microg/ml collagen LTA>or=31%: OR=4.7(2.9-7.7), p<0.0001]. In this prospective study on a large number of acute coronary syndrome patients undergoing stent implantation, we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist--AA, ADP, collagen--is an independent risk factor for 12-month cardiovascular death and non-fatal MI. Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences.

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.

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.

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.

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.

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.

This article evaluates the prevalence of cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Forty-one patients with a first episode of a retinal artery occlusion underwent complete ophthalmic examination, routine blood testing and specific laboratory tests for thrombophilia, such as fasting and postmethionine homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, factor VIII, factor V Leiden, factor II G20210A polymorphism, lupus anticoagulant and anticardiolipin antibodies. The control population consisted of 100 healthy individuals comparable as regards age and sex. At univariate analysis, hypertension, smoking, dyslipidaemia (both high cholesterol and triglyceride levels), antiphospholipid antibodies, hyperhomocysteinaemia, elevated factor VIII and lipoprotein(a) levels were significantly associated with retinal artery occlusion; at multivariate analysis, adjusted for age, sex, traditional and thrombophilic risk factors, smoking, hypercholesterolaemia, elevated homocysteine and lipoprotein(a) levels confirmed their independent role as risk factors for retinal artery occlusion. In conclusion, the results of the present pilot study demonstrate that the prevalence of hypercholesterolaemia and smoking and the 'thrombophilic burden' are increased in patients with retinal artery occlusion. Our findings may have implications for the management of these patients, suggesting the need for an intensive and tailored secondary prevention and new therapeutic approaches.

Background: Marfan syndrome is an inherited connective tissue disorder with an autosomic dominant transmission. The prevalence is 1:5000-10 000 and the clinical major criteria involve the skeletal and ocular apparatus and the cardiovascular and central nervous system. The main cause of morbidity is represented by the thoracic aortic dissection/aneurysm that is responsible for 80% of the deaths., Methods: We performed a clinical study on 227 patients enrolled at our Clinical and Research Marfan and Related Disorders Center. The aim of this study was to describe the prevalence of cardiovascular manifestation in this cohort of patients., Results: Aortic dilation was present in 172 patients (75.8%), mitral valve prolapse in 179 (78.9%). Aortic insufficiency was present in 83 patients (36.6%), mitral insufficiency in 165 (72.7%). When analyzed separately, in < 10-year and > 40-year patients aortic dilation was more prevalent than mitral valve prolapse. Three patients presented with interatrial septal defect, 4 aortic bicuspid valve; 23 had a history of ventricular and supraventricular arrhythmias, and in 2 patients an implantable cardioverter device had been implanted. Fifty-seven patients were treated with beta-blockers and 28 had been operated for aortic aneurysmal dilation., Conclusions: In Marfan syndrome mitral valve prolapse and aortic dilation are the main cardiovascular manifestations, interatrial septal defect and aortic bicuspid valve had the same prevalence than in subjects without Marfan syndrome. These data refer to our first patient evaluation; further studies are needed to evaluate the progression and the natural history of cardiovascular manifestations in Marfan syndrome.

Aims: The aim of this study was to evaluate (1) homocysteinemia and the prevalence of the C677T MTHFR polymorphism in Marfan patients and (2) whether the severity of cardiovascular manifestations is associated with homocysteinemia and/or C677T polymorphism., Methods and Results: We studied 107 patients subdivided into three subgroups based on the severity of cardiovascular manifestations: (A) no involvement (n=4); (B) mild involvement (n=45); (C) aortic dilatation or aortic dissection (n=58), and 189 controls. Total homocysteine (tHcy) was significantly higher in subgroup C than in subgroup B. In subgroup C patients with dissection tHcy was higher than in those without dissection. In subgroup C the prevalence of 677T homozygotes was higher, but not significantly, than in the subgroup B. In patients with dissection the prevalence of 677T homozygotes was significantly higher than in those without dissection and than in subgroup B. In the logistic regression analysis, severe cardiovascular manifestations and aortic dissection in Marfan patients were associated with tHcy plasma levels., Conclusions: Our data indicate an association between the severity of the cardiovascular manifestations, in particular aortic dissection, and elevated tHcy levels. This suggests an important role for tHcy in determining phenotypic variability in Marfan patients and provides further evidence for the association of homocysteinemia with the damage of the vascular system.

In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6–17) vs 15(9–25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. [ABSTRACT FROM AUTHOR]

Over the last decades, a considerable body of evidence supported the hypothesis that diet and dietary factors play a relevant role in the occurrence of diseases. To date, all the major scientific associations as well as the World Health Organization and the nonscientific organizations place an ever-increasing emphasis on the role of diet in preventing noncommunicable diseases. Many studies have evaluated the associations between food groups, foods, or nutrients and chronic diseases, and a consensus about the role of nutritional factors in the etiology of common diseases, such as cardiovascular and neoplastic diseases, has gradually emerged. Indeed, data from analytical and experimental studies indicated a relation between increased consumption of some food categories such as fruits and vegetables, fiber and whole grains, fish, and moderate consumption of alcohol and reduced risk of major chronic degenerative diseases, whereas increased total caloric intake, body weight, meat, and fats are associated with greater risk. However, the appropriate dietary strategy to prevent chronic degenerative diseases remains a challenging and a highly relevant issue. Recently, Mediterranean diet has been extensively reported to be associated with a favorable health outcome and a better quality of life. In the present review, we encompass the updated evidence of the beneficial effects of Mediterranean diet in the occurrence of major chronic degenerative diseases. © 2013 BioFactors, 39(4):335-342, 2013 [ABSTRACT FROM AUTHOR]

The authors point out the role of CYP2C19 loss-of-function allelles in the cardiovascular events that could be experienced by heart patients taking the antiplatelet clopidogrel. They cite the identified multiple chronic transient mechanisms involved in high on-clopidogrel platelet reactivity, including inadequate drug compliance, body mass index and drug-drug interactions. They also note two studies which confirmed the independent role of CYP2C19 as a determinant of major adverse cardiovascular events in patients taking clopidogrel.

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. [ABSTRACT FROM AUTHOR]

With longer average life expectancy, the prevalence of cardiovascular disease in later life is rising. A growing body of epidemiological evidence has shown a strong association between elevated homocysteine plasma levels and cardiovascular disease in the general population. This review focuses on the role of homocysteine as an emerging risk factor for cardiovascular disease in the elderly. The possibility of a relatively easy correction of hyperhomocysteinemia by vitamin supplementation represents an important stimulus to reach a definitive conclusion regarding the pathophysiological role of homocysteine as risk factor for cardiovascular disease in the general population and, in particular, elderly subjects. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for coronary artery disease; moreover, it increases systemic atherosclerotic burden by inducing the overexpression of inflammatory mediators, promoting endothelial damage, and impairing blood pressure regulation. Aim: Aim of this work was to evaluate whether a standardized evaluation of NAFLD improves cardiovascular risk assessment recognizing subclinical atherosclerosis in lower cardiovascular risk. Material and methods: We investigated NAFLD occurrence and severity, carotid and femoral intima-media-thickness (IMT) and vascular stiffness by ultrasound technique, endothelial function by peripheral-arterial-tonometry, lipid profile and inflammatory markers in 220 subjects (100 men, 120 women; 45.42±13.22 years old), without history of cardiovascular event, diabetes, liver infection, alcohol consumption, systemic diseases, and the use of drugs causing liver damage. NAFLD was evaluated, graded according to an eight-point scoring semi-quantitative severity score. Results and discussion: At univariate logistic analysis, NAFLD ≤ 3 score was significantly associated with pathological IMT, augmentation index, pulsewave-velocity at carotids and femoral arteries, and endothelial dysfunction, and this association was confirmed after adjustment for European Society of Cardiology Systematic Coronary Risk Evaluation (ESC SCORE) at multivariate analyses. Moreover, high sensitivity C-reactive protein levels were significantly higher in patients with at least 3 point steatosis, in comparison to the others. Receiver operating characteristic (ROC) curve analysis for NAFLD showed a significant higher area under curve for the detection of both early atherosclerotic burden and vascular stiffness, in comparison to ROC curve of ESC SCORE. Conclusions: According to our findings a NAFLD = 3 score was able to screen a subgroup with widespread morphological vascular damage and endothelial dysfunction in a primary prevention population. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

The aim of this study was to evaluate the effect of consuming gilthead sea bream fillets, with different n-6/n-3 ratios, on atherosclerotic biomarkers. Twenty healthy subjects were included in a randomised single-blinded cross-over trial. Participants were randomized into 2 groups, both of which received approximately 630 g per week of gilthead sea bream fed with either 100% fishmeal (FM) or partial replacement with plant proteins (PP) over two consecutive 10 week periods, respectively. Group A consumed firstly the FM fillets followed by the PP fillets, whereas the reverse order was adopted for group B. Group A reported a significant decrease of 29.3% (Δ = -26 mg/dL) in total cholesterol after the first phase of the intervention, before returning to baseline levels after the dietary intervention with fish fed with PP. Similarly, in group A, both LDL-cholesterol and triglycerides decreased significantly by 21.6% (Δ = -19 mg/dL) and 11.7% (Δ = -10.7 mg/dL), respectively, before increasing again after the intervention. Improvements in the inflammatory cytokines, interleukin-6 and -8 were also noted. Moreover, whole blood viscosity appeared significantly improved in group A, as seen by a significant increase of 7.59% (Δ = +4.59 mPA) for erythrocyte filtration rate. In conclusion, similar EPA+DHA content with different n- 6/n-3 ratio fish flesh intake was shown to have varied affects on lipid, inflammatory and haemorheological parameters in a group of healthy subjects. [ABSTRACT FROM AUTHOR]

Abstract: Background: An involvement of the renin angiotensin system in atrial fibrillation (AF) has been hypothesized, and ACE DD genotype has been suggested to influence the predisposition to AF. The aim of this study was to investigate the role of the ACE I/D polymorphism in relation to the different clinical forms of AF, lone and secondary nonvalvular atrial fibrillation (NVAF). Methods: 510 consecutive patients with documented NVAF (106 patients had lone, and 404 secondary NVAF), and 520 controls with a negative history of cardiovascular disease have been studied. Results: A significant difference in allele frequency between lone and secondary NVAF (p =0.002) has been found. The ACE D allele was associated with the predisposition to lone NVAF under a dominant, recessive and additive model, both at univariate and multivariate analysis, after adjustment for age and gender (multivariate analysis: dominant OR=2.87, p =0.02; recessive OR=2.01, p =0.003; additive OR=4.47, p <0.0001). ACE D allele was significantly associated with secondary NVAF at both univariate and multivariate analysis under a recessive and additive, but not dominant, model (multivariate analysis: recessive OR=1.89, p =0.001; additive OR=2.50, p <0.0001). Conclusions: This study highlights the role of ACE gene in predisposing to both lone and secondary NVAF, further contributing to penetrate the genetic mechanisms responsible for this complex disease. The clinical relevance of our results may be related to the possible characterization of subjects predisposed to NVAF in the absence of traditional risk factors, and to the use of ACE-inhibitors therapy able to improve the arrhythmogenic substrate. [Copyright &y& Elsevier]

: PurposeElevated lipoprotein(a) [Lp(a)] levels are a recognized risk factor for cardiovascular disease; however, little is known about their effects on venous thromboembolism.: MethodsWe conducted a case-control study of 603 adult patients with a history of venous thromboembolism (at least 6 months after the acute event) and 430 healthy subjects. We measured Lp(a), homocysteine, and antithrombin levels, factor V Leiden and factor II (prothrombin) polymorphisms, and anticardiolipin antibodies.: ResultsLp(a) levels >300 mg/L were found in 24% (n = 146) of the patients and in 13% (n = 58) of the controls (P = 0.005). In a multivariate analysis adjusted for acquired and hemostasis-related risk factors, there was an independent association between elevated (>300 mg/L) Lp(a) levels and venous thromboembolism (odds ratio = 2.1; 95% confidence interval: 1.4 to 3.2; P = 0.002). These results were confirmed in the 341 patients with idiopathic venous thromboembolism, as well as in those with recurrent thromboembolism.: ConclusionThese results show that Lp(a) is an independent risk factor for venous thromboembolism in adults, suggesting that it may be involved in the pathogenesis of idiopathic and recurrent disease. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "Intensive Oral Antiplatelet Therapy for Reduction of Ischaemic Events Including Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Intervention and Stenting in the TRITON-TIMI 38 Trial: A Subanalysis of a Randomised Trial" by S. D. Wiviott, E. Braunwald and E. McCabe in the April 19, 2008 issue.