Metabolic abnormalities linked to an increased cardiovascular risk are associated with high-grade prostate cancer: a single biopsy cohort analysis.

BACKGROUND: Smoking, hypertension, abdominal obesity and metabolic abnormalities have been considered individual factors involved in prostate cancer (PCa) pathogenesis. All of these factors are used to define the individual cardiovascular risk (CVR). The aim of our study was to evaluate the association between CVR and PCa diagnosis and grade among a consecutive series of men undergoing prostate biopsy. METHODS: From 2010 onwards, consecutive patients undergoing 12-core prostate biopsy were enrolled. Body mass index was measured before the biopsy. Blood samples were collected and tested for: PSA, fasting glucose, triglycerides and high-density lipoproteins. Blood pressure was also recorded. Metabolic syndrome was defined according to the Adult Treatment Panel III and CVR according to the European Association of Cardiologist Guidelines. We evaluated the association between CVR and PCa biopsy Gleason score using logistic regression analyses. RESULTS: Five hundred and eighty-four patients were enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with moderate/high CVR and 80 with low/no CVR (P=0.11). Out of the 237 patients with PCa, 113 had a Gleason score 6 and 124 a Gleason score ⩾7. Out of them, 92/124 (75%) presented a moderate/high CVR (P=0.004). Moderate/high CVR was not associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence interval (CI): 0.474-1.156; P=0.186) but with an increased risk of Gleason score ⩾7 (OR: 2.154, CI: 1.076-4.314; P=0.030). CONCLUSIONS: In our study, a moderate/high CVR is associated with an increased risk of a high-grade Gleason score when PCa is diagnosed on biopsy. Although these results should be confirmed in multicentre studies, patients with moderate/high CVR should be carefully evaluated for PCa diagnosis.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Structure, production and function of erythropoietin: implications for therapeutical use in cardiovascular disease.

Erythropoietin (EPO) is a 30,400 daltons glycoprotein, consisting of 165 amino acids produced mainly in the kidney and in the liver and regulating erythrocyitosis. It primarily acts on erythroid precursor cell at colony-forming units-erythroid stage inhibiting the apoptosis. EPO binds on a specific membrane receptor thereby activating at least three specific intracellular signaling pathways, such as phosphatidylinositol 3-kinase/ protein kinase B, Ras-mitogen-activated protein kinase and some members of the signal transducers and activators of transcription family. In addition to kidney and liver, EPO mRNA has been detected in other tissues; accordingly EPO receptor has been identified in several type of cells and recent reports have suggested new roles for EPO in non-haematopoietic tissues with a robust evidence for neuroprotective and cardioprotective activity. In different animal models, in vitro, in isolated perfused heart and in vivo, recombinant human erythropoietin protects heart from ischemia reperfusion injury and reduces myocardial damage. EPO tissue protective activity can be separated from erythropoietic activity. Molecules owing the first property but not the second one have been described. In patients with acute myocardial infarction serum EPO level correlates inversely with infarct size. Acute coronary syndrome, extracorporeal circulation and percutaneous coronary intervention are potential fields of application for tissue protective EPO activity to reduce myocardial damage, increase cardiac function ad improve outcome.

Metabolomic fingerprinting of plant extracts.

The standardization and quality control of plant extracts is an important topic, in particular, when such extracts are used for medicinal purposes. Consequently, the development of fast and effective analytical methods for metabolomic fingerprinting of plant extracts is of high interest. In this investigation, electrospray mass spectrometry (ESI-MS) and (1)H NMR techniques were employed with further statistical analyses of the acquired data. The results showed that negative ion mode ESI-MS is particularly effective for characterization of plant extracts. Different samples of the same species appear well-clustered and separated from the other species. To verify the effectiveness of the method, two other batches of extracts from a species, in which the principal components were already identified (Cynara scolymus), were analyzed, and the components that were verified by the principal component analysis (PCA) were found to be within the region identified as characteristic of Cynara Scolymus extracts. The data from extracts of the other species were well separated from those pertaining to the species previously characterized. Only the case of a species that was strictly correlated from a botanical point of view, with extracts that were previously analyzed, showed overlapping.

Evaluation of glyoxal and methylglyoxal levels in uremic patients under peritoneal dialysis.

Advanced glycation end products (AGEs) accumulate in serum and tissues of patients with chronic renal failure, even in the absence of diabetes, and a different clearance of these species has been observed by hemodialysis and peritoneal dialysis (CAPD). Furthermore, it has been shown that not only AGE but also 1,2-dicarbonyl compounds are formed during heat sterilization of glucose-based peritoneal dialysis fluids. Therefore, we investigated the level of some AGEs (pentosidine and free pentosidine) and dicarbonyl compounds (glyoxal and methylglyoxal) in end-stage renal disease patients subjected to peritoneal dialysis. Samples (20 from healthy subjects, 16 from uremic patients before and after 12 h of peritoneal dialysis) were analyzed, and the plasma and dialysate levels of glyoxal, methylglyoxal, pentosidine, and free pentosidine were determined. In plasma of uremic patients, mean values of pentosidine showed a small decrease after dialysis and were always higher than those of healthy control subjects. An analogous trend was observed for free pentosidine. In the case of peritoneal dialysate, no pentosidine and free pentosidine were found at time zero, whereas both compounds were detected after 12 h of dialysis. Glyoxal and methylglyoxal mean levels showed a decrease in plasma after dialysis even if their values were always higher than those of healthy control subjects. Surprisingly, an analogous trend was observed also in dialysate. These results might indicate that glyoxal and methylglyoxal already present in the dialysis fluid react with the peritoneal matrix proteins, accounting for the gradual loss of peritoneal membrane function that is often observed in patients subjected to CAPD for a long time.

Advanced glycation end products/peptides: an in vivo investigation.

Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.

Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women.

Women who develop acute myocardial infarction (AMI) at a young age have fewer classical risk factors and less coronary stenosis than older women. In this rare population, it is plausible that a heightened hemostatic system may play an important mechanistic role in thrombus formation and in the development of AMI. We chose to investigate whether or not there is an association between premature AMI and the plasma concentrations of five hemostatic measurements that had been previously established as risk factors for AMI, and of the inflammation marker C-reactive protein (CRP). Women who had survived AMI at the age of 45 years or less (n = 141) were drawn from those admitted to 125 Italian coronary care units over a 3-year period. In them, and in an equal number of controls, plasma levels of immunoreactive tissue plasminogen activator (tPA), plasminogen activation inhibitor 1 (PAI-1), von Willebrand factor (VWF), fibrinogen, D-dimer and CRP were measured. Higher levels of VWF, fibrinogen, CRP and tPA were associated with AMI. After adjustment for both classical and hemostatic risk factors, only tPA maintained an independent association with AMI: the odds ratios (taken as an index of relative risk) for tPA values in the middle and higher tertiles were 2.86 (CI 1.63-5.02) and 8.18 (CI 2.66-25.20), respectively. In conclusion, there is a strong association between non-fatal AMI and increased plasma levels of tPA antigen. This finding is thought to be the expression of a reduced rather than enhanced fibrinolytic activity.

A matrix-assisted laser desorption/ionization mass spectrometry study of the non-enzymatic glycation products of human globins in diabetes.

The molecular species present in globins from healthy and diabetic subjects with and without chronic complications have been analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The technique demonstrated the presence of glycated and glyco-oxidated species of both alpha- and beta-globins. Their abundances show a good linear relationship with respect to HbA1c values and with the mean daily plasma glucose levels over the 6 weeks preceding the investigation. Interestingly, slightly different behaviour is observed in the data from patients with and without chronic complications; the plots of HbA1c vs. the abundance of glycated and glyco-oxidated species show different slopes and different intercepts with the y-axis. To investigate this aspect the mean abundances of glyco-oxidated species from healthy subjects and from diabetic patients with and without complications were calculated. Higher values were found for the two last sets of samples, but no significant difference was found between them. These data could indicate different individual proclivities to oxidation and/or different oxidation kinetics related to behavioural and environmental factors.

The complexity of non-enzymatic glycation product sets of human globins.

AIMS/HYPOTHESIS: Recently an individual variability in the relationships between mean blood glucose levels and HbA1c has been observed among diabetic patients. The aim of this study was to provide an accurate description and evaluation of glycated and glyco-oxidated globins from diabetic subjects and their relationship with HbA1c and plasma glucose values. METHODS: We studied 20 type 2 diabetic and 10 healthy subjects. Plasma samples were analysed by matrix-assisted laser desorption ionisation mass spectrometry. RESULTS: The presence of glycated and glyco-oxidated species of both alpha and beta globin was demonstrated. Values for these showed a good linear relationship with HbA1c values and the mean daily plasma glucose values for the 6 weeks preceding the investigation. Trends differed according to whether patients had chronic complications or not, differences being seen in the slopes of the plots relating HbA1c to the abundance of glycated and glyco-oxidated species. CONCLUSIONS/INTERPRETATION: The data obtained are consistent with the concept that individuals have a different individual proclivity for oxidation and/or that different oxidation kinetics are related to behavioural and environmental factors. Our data are thus relevant to the analysis of phenotype differences in diabetic patients.

[Reporting echocardiography exams with the G8-Cardio ANMCO software]. / Refertazione dell'esame ecocardiografico con il software G8-Cardio ANMCO.

BACKGROUND: The availability of a common computerized program for echocardiographic study archiving and reporting at national and/or international level could make it possible to standardize the echo reports of different echocardiographic laboratories, and to use the wealth of data thus obtainable with echocardiography, and to exploit its capillary territorial distribution, with the aim of collecting echocardiographic data in a standard format for epidemiological, scientific and administrative purposes. METHODS: To develop such a software, an ad hoc joint National Association of Hospital Cardiologists and Italian Society of Echocardiography task force worked in conjunction with the Italian Branch of Agilent Technologies to standardize the phraseology of accepted echocardiographic terms and of the quantitative parameters derived from transthoracic and transesophageal echocardiographic examination at rest as well as during exercise and pharmacological stress, and to develop an ad hoc software. This echocardiographic study archiving and reporting program is part of the whole G8-Cardio ANMCO software developed to computerize the whole cardiological chart. The software has been developed by Agilent Technologies to provide a fast, easy-access and easy to use report generator for the non-computer specialist using DBMS Oracle 7.3 database and Power Builder 5.0 to develop a user-friendly interface. RESULTS: The number of qualitative and quantitative variables contained in the program is 733 for echocardiography at rest, while it depends on the stressor and on the length of the examination for the stress echo (dipyridamole 214-384, dobutamine 236-406, exercise 198-392). The program was tested and refined in our laboratory between November 1999 and May 2000. During this time period, 291 resting and 56 stress echocardiographic studies were reported and recorded in a database. On average, each resting echocardiographic study lasting 10 +/- 4 (range 5-17) min was recorded using 50 +/- 11 (range 33-67) variables and 41,566 bytes of hard-disk memory space. Stress echocardiographic studies, each lasting 7 +/- 5 (range 5-21) min, were recorded using 143 +/- 74 (range 38-194) variables and 38,531 bytes of hard-disk memory space. CONCLUSIONS: To our knowledge this software represents the first experience of a common computerized program for echo archiving and reporting carried out at national level.

[Atherosclerosis and simvastatin: new questions for the new millennium]. / Aterosclerosi e simvastatina: nuovi interrogativi per il nuovo millennio.

Coronary artery disease is still associated with high morbidity and mortality in Western countries. Lipid blood levels have a tight correlation with the risk of coronary events, and the results of many trials on lipid-lowering therapy (and particularly on simvastatin) demonstrated a significant reduction in total and cardiac mortality, and in the incidence of myocardial infarction and coronary events; even the progression of coronary stenosis has been reduced by treatment with statins. Beyond cholesterol reduction, simvastatin exerts many favorable effects on endothelial function, inflammatory activity, expression of pro-thrombotic factors and oxidative stress, yielding a rational basis for its important clinical positive effects, both in primary and secondary prevention of coronary disease. Future developments, which are the subjects of many planned or ongoing clinical trials, are related to the treatment of high-risk patients, the evaluation of the efficacy of elevated simvastatin dosages and of a deep reduction in cholesterol blood levels, the interaction between simvastatin and other drugs (antioxidant compounds, vitamins, antiplatelet drugs) or interventional procedures (percutaneous transluminal coronary angioplasty). Particularly, the Heart Protection Study, the A to Z trial, and the SEARCH and SMART studies will provide important data on a wider, earlier and greater use of simvastatin, which has been demonstrated effective both in the prevention and treatment of acute coronary syndromes.

[The role of biochemical markers of myocardial damage in clinical practice: the diagnosis of infarct and risk stratification. The Intersociety Interdisciplinary Study Group of the ANMCO-SIBioC-SIMeL, Markers of Muocardial Lesions. L'Associazione Nazionale Medici Cardiologi Ospedalieri-Società Italiana di Biochimica Clinica-Società Italiana di Medicina di Laboratorio]. / Ruolo dei marcatori biochimici di danno miocardico nella pratica clinica: diagnosi di infarto e stratificazione del rischio. Gruppo di Studio Interdisciplinare Intersocietario ANMCO-SIBioC-SIMeL "Marcatori di Lesione Miocardica".

For many years creatine kinase (CK) and CK-MB isoenzymes were used together with the ECG to confirm the presence of myocardial infarction. During the last decade newer cardiac markers have been introduced and immunological test systems developed for their quantification. Among these new markers, a prominent role has emerged for cardiac troponins (T or I). These technological advanced assays have shown greater sensitivity compared to "conventional cardiac enzymes;, thereby identifying patients with small--at times, microscopic--infarcts who would not have met defining criteria for myocardial infarction in an earlier era. Another major advantage shown by both cardiac troponins with respect to "conventional cardiac enzymes" is their ability to predict clinical outcome over a short- or long-term follow-up in patients with acute coronary syndromes, and this appears to be particularly relevant in patients with micronecrosis, who constitute a high-risk subgroup of unstable angina patients. Recently, myoglobin has also been widely applied as a marker. Although lacking in myocardial specificity, it is the earliest marker to show an increase after coronary occlusion. Thus, the combined use of myoglobin and a cardiospecific structural protein such as troponin T or I may prove an attractive strategy for biochemical testing in chest pain patients. With the routine use of these novel cardiac markers, fascinating opportunities are now open in the field of diagnostic classification (making the World Health Organization definition of myocardial infarction obsolete) and risk stratification in chest pain patients; opportunities that were unforeseen in the era of cardiac enzymes. However, the use of these markers has also posed some important questions on: a) the best and most cost-effective diagnostic strategy in chest pain patients; b) the remaining role of cardiac enzymes; c) the therapeutic consequences of a positive test result.

The effect of verapamil on left ventricular remodelling and diastolic function after acute myocardial infarction (the Verapamil Infarction Study on Remodelling and Relaxation--VISOR).

The VISOR is a double blind, randomized, placebo-controlled study aimed to assess the effects of early and prolonged administration of verapamil on the left ventricular geometry and diastolic function in patients with anterior acute myocardial infarction treated with thrombolysis. Patients with heart failure or ejection fraction < 45% were excluded. Within 12 hours from starting thrombolysis, 70 patients were given verapamil (5 mg/hour intravenously for the first 24 hours, followed by 120 mg t.i.d. perorally for 6 months) or equivalent placebo. Echocardiograms were performed on admittance, before discharge, after 3 months and 6 months. The following parameters were calculated: left ventricular volumes, ejection fraction, sphericity index, early (E) and late (A) transmitral peak flow velocities and time-velocity integrals with their ratios, deceleration time and half-time of E, isovolumic relaxation time (IVRT), and non-invasive time constant of ventricular relaxation (tau). The basal and the last available parameters were considered for statistical analysis. The effects of the treatment on the left ventricular volumes, ejection fraction, and sphericity index were not statistically relevant. Conversely, a reduction of E/A ratio (P < .05) and increases of A integral (P < .01), deceleration time and half-time of E, IVRT and tau (P < .05) were found in the placebo group and not in the verapamil group. No significant changes in the blood pressure, heart rate, PQ interval, and biochemical parameters were observed in the two groups. In conclusion, in patients with a thrombolysed anterior acute myocardial infarction and preserved systolic function, verapamil can prevent alterations of the diastolic function in absence of effect on ventricular remodelling, and has a good safety profile.