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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. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels. DESIGN:: Cross-sectional. SETTING:: Population-based study. SUBJECTS:: A sample of 520 clinically healthy subjects (211 males, 309 females) with a mean age of 46?y, living in Florence area, Italy. INTERVENTIONS:: Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. Fasting blood samples were drawn for assessment of lipid profile, homocysteine and circulating vitamins. RESULTS:: Contribution from total fats was over 30%in about 70%of subjects and intake of saturated fatty acids (SFA) was above the recommended values in at least 40%of the study population. Furthermore, almost the whole (99.6%) population reported low intake of polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present in over 40%of the study population, whereas abnormal values of LDL-cholesterol were observed in about 30%. High levels of homocysteine were found in 11.7%of the study population. An extremely high percentage of subjects reported low intake of vitamins, especially with regard to folic acid (89%), vitamin B6 (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating levels of vitamin B12 and folic acid, and intake of alcohol and vitamin C resulted in being independently associated with homocysteine plasma levels. CONCLUSIONS:: In a typical Mediterranean country, general outlines of Mediterranean diet are not completely followed, especially concerning total fats, SFA, PUFA and vitamins'intake. SPONSORSHIP:: Ministero della Salute (Italy)-‘Progetto per la Salute e la Prevenzione di Malattia’2001-2003.European Journal of Clinical Nutrition (2005) 59, 584-591. doi:10.1038/sj.ejcn.1602112 Published online 2 March 2005 [ABSTRACT FROM AUTHOR]

Background: In patients with heart failure, impairment of baroreflex function occurs early and contributes to sympathetic activation, however, at present its prognostic role has not been definitively established.Aims: To evaluate the prognostic significance of baroceptor impairment in patients with different degrees of heart failure.Methods: We enrolled 52 consecutive patients with heart failure, referred to our institution for functional evaluation. Twenty-eight suffered from ischemic cardiomyopathy and 26 from dilated cardiomyopathy. Thirteen patients were in NYHA class I, 20 in NYHA class II and 19 in class III. All patients underwent baroreflex assessment by phase IV Valsalva manoeuvre using Finapres finger monitoring of arterial blood pressure, echocardiography [with evaluation of left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD) and mean pulmonary artery pressure] and functional evaluation by cardiopulmonary exercise test and 6-min walk corridor test within 2 days of hospital admission.Results: Mean duration of follow-up was 26 months (range 6-35 months). At baseline, evaluation in 13 patients BRS was normal (>5 ms/mmHg), in 17 moderately impaired (1.5-5 ms/mmHg) and in 22 severely depressed (<1.5 ms/mmHg). Baroreflex function was relatively preserved in patients in NYHA class I (5.1+/-2.5) in comparison to patients in NYHA class II and III (2.1+/-2.3 and 2.08+/-1.9 ms/mmHg, respectively). Of the 52 patients who entered the study at the end of follow-up 15 died of cardiac cause and 5 underwent heart transplantation. Survival free from heart transplantation was 62% in patients with normal baroreflex function, 62% in patients with moderate impairment of baroreflex and 66% in patients with major derangement. NYHA class, LVEF, LVFS and LVEDD were significantly associated with event free survival while baroreflex function was not.Conclusions: Our results suggest that evaluation of BRS impairment by phase IV Valsalva manoeuvre has limited prognostic value in patients with heart failure. [ABSTRACT FROM AUTHOR]

Guglielmina Pepe,1,2 Betti Giusti,1,2 Elena Sticchi,1,2 Rosanna Abbate,1,2 Gian Franco Gensini,1–3 Stefano Nistri2,4 1Department of Experimental and Clinical Medicine, Section of Critical Medical Care and Medical Specialities, DENOTHE Center, University of Florence, 2Cardiothoracovascular Department, Marfan Syndrome and Related Disorders Regional Referral Center, Careggi Hospital, 3Santa Maria agli Ulivi, Fondazione Don Carlo Gnocchi, Onlus, Institute for Cancer Research and Treatment, Florence, 4Cardiology Service, CMSR Veneto Medica, Altavilla Vicentina, Italy Abstract: Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity. Keywords: Marfan syndrome, thoracic aortic aneurysm, fibrillin 1, cardiovascular manifestations, diagnosis, therapy

399 out of 474 inpatients with unstable angina were monitored for 48 h and 97 of these were found to be refractory to conventional antianginal treatments and entered a randomised double-blind study. With the initial protocol heparin infusion or bolus were compared with aspirin; with a modified protocol, heparin infusion, the best of these three treatments, was compared with alteplase. Patients were monitored for 3 days after starting treatment and then observed clinically for 4 more days. On the first days of treatment heparin infusion significantly decreased the frequency of angina (by 84-94%), episodes of silent ischaemia (by 71-77%), and the overall duration of ischaemia (by 81-86%). Heparin bolus and aspirin were not effective. Alteplase caused small (non-significant) reductions on the first day only. Only minor bleeding complications occurred. [ABSTRACT FROM AUTHOR]

Background The economic evaluation of the results of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Artery (GUSTO) trial found that recombinant tissue plasminogen activator is more cost-effective than streptokinase for the treatment of acute myocardial infarction.Aim We evaluated the impact on a cost effectiveness analysis, of the differences in the cost of thrombolytics among countries and of differences in efficacy across patient subgroups.Methods We considered the crude costs of streptokinase and recombinant tissue plasminogen activator in Germany, Italy, the United Kingdom, and the United States of America, and the 30-day mortality found in the GUSTO trial. We calculated the incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator. We also calculated the incremental costs for each life saved for two protocols implying a selective use of streptokinase and recombinant tissue plasminogen activator (age-selective protocol: recombinant tissue plasminogen activator in patients ≤75 years, streptokinase in older patients; site-selective protocol: recombinant tissue plasminogen activator in anterior acute myocardial infarction, streptokinase in non-anterior acute myocardial infarction).Results The incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator in all GUSTO patients vary greatly among countries: the incremental costs for each life saved are 31%, 45%, and 97% higher in Germany, Italy, and the United States of America compared to the United Kingdom. The use of a site-selective protocol implies a halved cost-effectiveness ratio compared to the use of recombinant tissue plasminogen activator in all cases of acute myocardial infarction.Conclusions(1) The cost-efficacy of recombinant tissue plasminogen activator vs streptokinase in acute myocardial infarction varies greatly among countries due to differences in the cost of drugs. (2) A selective use of thrombolytics for some sites of infarction is more cost-effective than the exclusive use of recombinant tissue plasminogen activator. [ABSTRACT FROM PUBLISHER]

Reliability and reproducibility of a new automatic ambulatory blood pressure recorder were tested on 31 subjects (18 normotensives and 13 hypertensives). Of 3688 recordings, 1424 measurements were cross-checked with a sphygmomanometer in standing or sitting position at the beginning and at the end of a twenty-four hour monitoring period. In the normotensive subjects cross-checkings were performed also during a treadmill exercise stress test. Analysis of variance did not indicate statistical differences between the two types of measurement (p>0.09 for systolic and p>0.62 for diastolic), and a significant linear correlation was found at rest (r = 0.99, p<0.001 for systolic and r=0.98, p>0.001 for diastolic pressure). During the effort test the device was unable to correctly measure blood pressure values after the first step. During the twenty-four hour monitoring period only 1.1 % of the preprogrammed measurements were lost for each subject. The recorder seems to be a suitable and reliable tool for automatic blood pressure monitoring. [ABSTRACT FROM AUTHOR]

To evaluate blood pressure reactivity in children and its changes in adolescents, the acute pressor response to a video-game stress test and the noninvasive ambulatory blood pressure monitoring were evaluated in 62 healthy children divided into three age groups. Basal blood pressure values were measured according to the NIH Task Force. With baseline measures and body mass index controlled for, analysis of covariance showed that the video game provoked significant and incremental cardiovascular reactivity across the games in adolescents when compared with the two other groups of children. The same group of children showed also a significantly higher systolic ambulatory pressure during the daytime, whereas no significant difference was observed by basal BP measurement. In conclusion an increased reactivity to external stimuli was observed in adolescents, and this pattern was strictly associated with a higher daily blood pressure. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about complementary and alternative medicine.

Giorgio Galanti,1 Laura Stefani,1 Gianfranco Gensini2 1Sports Medicine Center, 2Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Background: Breast and colon tumors are the most common types of cancer in the general population. As a result of improved diagnosis and treatment, more people are now surviving cancer. Lifestyle has been identified as one of the potential risk factors for cancer, and it has been demonstrated recently that physical activity reduces the physiological and psychological symptoms and side effects of chemotherapy. Muscular atrophy, weight changes, decreased aerobic capacity, fatigue, and depression are the most common symptoms in cancer patients. The exact amount of moderate to vigorous physical activity needed to overcome these effects has not yet been established, but an individualized and variable exercise program as prescription therapy could be considered a helpful tool for improving quality of life. This paper proposes a model of lifestyle analysis and dedicated individualized exercise programs for the treatment of cancer patients. The program starts with a preliminary evaluation of the patient’s lifestyle using a questionnaire and accelerometer, which provides information on the amount of daily physical activity and number of steps taken, as well as an assessment of aerobic capacity, cardiovascular response, muscle strength, and resistance. Two different levels of aerobic exercise, ie, low-to-moderate (40% of maximal heart rate) to moderate (60% of maximal heart rate) can be prescribed. This model of exercise prescription in patients with cancer offers a flexible program for assisting in the management of this complex disease. It is projected to ensure easier management of medical problems related to cancer, and to attract a greater number of participants over time. Keywords: physical exercise, therapy, breast cancer, colon cancer, lifestyle