Determinants of fibrinogen in an Italian population suffering from claudication. Lower fibrinogen in the south compared to middle and north of Italy. The ADEP Group.

Prospective studies have shown that high plasma levels of fibrinogen are independently associated with the risk of cardiovascular complications. In patients suffering from peripheral vascular disease (PVD) fibrinogen has been shown to be an independent predictor of cardiovascular disease but its determinants have never been examined in this clinical setting. DESIGN AND METHODS: Fibrinogen levels were related to clinical and laboratory variables in 2,111 patients suffering from PVD. We also analyzed whether there was a regional distribution of risk factors. RESULTS: The median values of fibrinogen was 312 mg/dL. The clinical variables examined did not differentiate patients with elevated or normal fibrinogen levels. In particular, patients with ankle/arm pressure ratio < 0.8 did not show a higher prevalence of fibrinogen > 312 mg/dL. Conversely, white blood cell (WBC) count and serum cholesterol levels were significantly associated with high fibrinogen levels (p < 0.0001). Multiple logistic regression analysis demonstrated that areas of Italy were differently associated with high plasma fibrinogen levels (p < 0.03): subjects in the north and middle of Italy having significantly higher values of fibrinogen than subjects in the south of Italy (p < 0.01). A similar regional distribution was observed for WBC count and serum cholesterol levels. INTERPRETATION AND CONCLUSIONS: The regional distribution of risk factors raises the question as to whether the already reported large variability of cardiovascular events so in PVD may be attributed to a non homogeneous distribution of risk factors

Low-density lipoprotein-lowering medication and platelet function

Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic patients have been shown to interfere with platelet function. Several studies, in fact, suggested that statins exert anti-thrombotic effects largely as a result of an anti-platelet activity. Among the other LDL-C-lowering agents those acting by interfering with cholesterol reabsorption from the gut (cholestyramine, colestipol) do not appear to interfere with platelet function, whereas peroxisome proliferator-activated receptor agonists (such as fibrates) can inhibit platelet function. The full potential of these drugs in vascular protection is only just being realized. Further studies are still needed to elucidate the full therapeutic benefits of these agents in plaque stabilization and thrombosis. Copyright (c) 2006 S. Karger AG, Basel

Influence of the oral status on cardiovascular diseases in an older Italian population

Oral diseases have been adversely associated with cardiovascular diseases (CVD), which are also the most frequent cause of death in older population. The aim of this study was to investigate the association among oral status indexes and CVD in patients aged more than 65 years attending in the Oral department of a public hospital Policlinico Umberto 1 of Rome. The study population consisted of 533 patients. Dental status was detected measuring the Decayed, Missing, and Filled Teeth (DMFT) and Community Periodontal Index (CPI) indexes. The chi-square test with a 95% confidence level was used to assess qualitative variables. Odds ratios (ORs) and stepwise logistic regression were used to calculate risk estimates; the independent variables: age, gender, DMFT, CPI index, Geriatric Oral Health Assessment Index (GOHAI) score, and tooth loss were included in the statistical model. P value <0.05 was considered a statistically significant cut-off. No differences were found between females and males for DMFT and CPI. GOHAI data were worst for females. Patients with CVD had less education and oral care (P < 0.05), and higher CPI index and number of missing teeth (P < 0.05). Data show that patients with more than 18 missing teeth have 2.5 times greater risk of CVD. CVDs are associated with type 2 diabetes mellitus, underweight, and obesity (P < 0.05). From the findings of this study, it can be confirmed a significant link between CVD and oral health. A cooperation among geriatrician, cardiologist, and dentist is suitable to counteract the development of CVD and to early identify patients at risk of CVD

Oxidant stress and platelet activation in hypercholesterolemia

Hypercholesterolemia is the dominant risk factor associated with atherothrombotic disorders in the western world. Consequently, much attention has been devoted to defining its role in the pathogenesis of atherosclerosis. It is currently recognized that hypercholesterolemia induces phenotypic changes in the microcirculation that are consistent with oxidative and nitrosative stresses. Superoxide is generated via several cellular systems and, once formed, participates in a number of reactions, yielding various free radicals, such as hydrogen peroxide, peroxynitrite, or oxidized low-density lipoproteins. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, such as platelet activation and lipid peroxidation, which are both involved in the initiation and progression of the atherosclerotic lesions. Thus, therapeutic strategies that act to maintain the normal balance in the oxidant status of the vascular bed may prove effective in reducing the deleterious consequences of hypercholesterolemia

Platelet activation in type 2 diabetes mellitus

The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, prothrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. © 2004 International Society on Thrombosis and Haemostasis

Comparison between “early” or “late” intravitreal injection of dexamethasone implant in branch (BRVO) or central (CRVO) retinal vein occlusion: six months follow-up

AIM: The aim of this study was to compare early and late injections of intravitreal dexamethasone implant in patients affected by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) with a six-months follow-up. We assessed whether an earlier treatment start (within seven days from diagnosis) could be more beneficial than a delayed (or late) treatment start (after seven days). MATERIALS AND METHODS: The study included 81 patients (81 eyes) affected by retinal vein occlusion. Best corrected visual acuity was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS) while central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. RESULTS: Both types of patients had a positive therapeutic response to dexamethasone, with an increase in visual acuity (ETDRS) and CMT reduction. CRVO patients were characterized by lower ETDRS values at baseline and at the end of the follow-up as compared to BRVO. CRVO patients showed higher CMT values at baseline, after three and six months from injection. No significant differences in therapeutic response to dexamethasone were observed between patients treated early or late, regardless of RVO type. CONCLUSIONS: This study demonstrates that the therapeutic properties of dexamethasone implant are not significantly influenced by an early or late treatment start in patients affected by BRVO and CRVO, although its therapeutic efficacy seems greater in the former type

LexMeter. Validation of an automated system for the assessment of lexical competence of medical students as a prerequisite for the development of an adaptive e-learning system

Distance learning is used in medical education, even if some recent meta-analyses indicated that it is no more effective than traditional methods. To exploit the technological capabilities, adaptive distance learning systems aim to bridge the gap between the educational offer and the learner’s need. A decrease of lexical competence has been noted in many western countries, so lexical competence could be a possible target for adaptation. The “Adaptive message learning” project (Am-learning) is aimed at designing and implementing an adaptive e-learning system, driven by lexical competence. The goal of the project is to modulate texts according to the estimated skill of learners, to allow a better comprehension. LexMeter is the first of the four modules of the Am-learning system. It outlines an initial profile of the learner’s lexical competence and can also produce cloze tests, a test based on a completion task. A validation test of LexMeter was run on 443 medical students of the first, third, and sixth year at the University “Sapienza” of Rome. Six cloze tests were automatically produced, with 10 gaps each. The tests were different for each year and with varying levels of difficulty. A last cloze test was manually created as a control. The difference of the mean score between the easy tests and the tests with a medium level of difficulty was statistically significant for the third year students but not for first and sixth year. The score of the automatically generated tests showed a slight but significant correlation with the control test. The reliability (Cronbach alpha) of the different tests fluctuated under and above 0.60, as an acceptable level. In fact, classical item analysis revealed that the tests were on the average too simple. Lexical competence is a relevant outcome and its assessment allows an early detection of students at risk. Cloze tests can also be used to assess specific knowledge of technical jargon and to train reasoning skill

The interplay between antioxidants and the immune system. A promising field, still looking for answers

Editoriale su review inerente il ruolo del resveratrolo e degli antiossidanti nelle risposta immun

Outcome of very elderly (octogenarians) patients with coronary artery disease, all diagnosed by coronary angiography

Background: Women with ischemic heart disease (IHD) typically present less severe coronary artery atherosclerosis. Despite that, as compared with men, women maintain a worse outcome. This female susceptibility seems to be mainly related to older age of clinical presentation and heavier risk factors burden. Purpose: To investigate whether sex differences exist in the real-world management and clinical outcome of elderly patients with suspected IHD. Methods: Retrospective analysis of IHD elderly (≥ 80 years) patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina (SA). Management strategy, including invasive revascularization or a conservative medical approach, and outcome were evaluated. Results: A total of 1420 (41% women; mean age: 83.1 ± 2.8) IHD patients referring for ACS (43%) and SA (57%) were analyzed. Men more likely accessed for SA (59.6% vs 52.5%, p<0.001) whereas ACS was the most frequent reason for angiography in women (28.8% vs 21.5%, p<0.001). No significant sex differences in the burden of obstructive epicardial disease were observed in both ACS and SA patients. No sex disparities in antiplatelet therapy, specifically clopidogrel, were detected. Compared with SA men patients, female ones received more likely a conservative therapy (p=0.049). After a median (IQR) follow-up time of 39.0 (16-71) months, a total of 514 (36%) patients died. No sex differences in cardiac death (p=0.139) was observed. Nevertheless, the Kaplan Meier curves showed a trend in lower all-cause mortality in female group(p=0.093). Conclusions: In the very elderly population, an invasive strategy is superior to a conservative one in terms of survival rate. However, a dilution of the efficacy occurs with increasing age and comorbidities, and for male patients the benefit of the invasive strategy is not clear. Prospective studies are warranted to evaluate the net benefit of an invasive or a conservative approach in older population

Reply to: Platelet function in patients with cirrhosis

n/